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__NOTOC__
{{CMG}}; {{AE}} {{VKG}}
'''''Synonyms and Keywords:''''' Aarskog disease, Aarskog-Scott syndrome, AAS, Faciodigitogenital syndrome, Faciogenital dysplasia, FGDY, Scott Aarskog syndrome
'''''Synonyms and Keywords:''''' Aarskog disease, Aarskog-Scott syndrome, AAS, Faciodigitogenital syndrome, Faciogenital dysplasia, FGDY, Scott Aarskog syndrome
== Overview ==
== Overview ==
'''Aarskog-Scott syndrome''' is a rare [[inherited disease]] distinguish by [[short stature]], [[facial]] abnormalities, [[Skeleton|skeletal]] and [[genital]] anomalies. The Aarskog-Scott syndrome (AAS) is also known as the Aarskog syndrome, faciodigitogenital syndrome, shawl [[scrotum]] syndrome and facial [[genital]] [[dysplasia]]. In The United States of America in order to categorise a [[condition]] as a [[rare disease]] it should affect fewer than 200,000 people. [[Rare diseases]] also called as [[Orphan disease|orphan diseases]]. [[Orphan Drug Act]] was passed on 1983 by congress for the [[rare diseases]]. Today an average of 25-30 million americans have been reported with [[rare diseases]]. The number of people with individual [[rare disease]] may be less but overall the number of people with [[rare diseases]] are large in number.
'''Aarskog-Scott syndrome''' is a rare [[inherited disease]] distinguish by [[short stature]], [[facial]] abnormalities, [[Skeleton|skeletal]] and [[genital]] anomalies. The Aarskog-Scott syndrome (AAS) is also known as the Aarskog syndrome, faciodigitogenital syndrome, shawl [[scrotum]] syndrome and facial [[genital]] [[dysplasia]]. In The United States of America in order to categorise a [[condition]] as a [[rare disease]] it should affect fewer than 200,000 people. [[Rare diseases]] also called as [[Orphan disease|orphan diseases]]. [[Orphan Drug Act]] was passed on 1983 by congress for the [[rare diseases]]. Today an average of 25-30 million americans have been reported with [[rare diseases]]. The number of people with individual [[rare disease]] may be less but overall the number of people with [[rare diseases]] are large in number.
== Historical Perspective ==
== Historical Perspective ==
* In 1970, Aarskog-Scott syndrome (AAS) was first described by Aarskog, a Norwegian [[pediatrician]] and human [[geneticist]].
* In 1970, Aarskog-Scott syndrome (AAS) was first described by Aarskog, a Norwegian [[pediatrician]] and human [[geneticist]].
*In 1971, Scott described the association between [[Ligamentous laxity|ligamentous]] laxity which results in hyperextensibility of the fingers, [[genu recurvatum]], flat feet and Aarskog-Scott syndrome (AAS).<ref name="pmid5173168">{{cite journal| author=Scott CI| title=Unusual facies, joint hypermobility, genital anomaly and short stature: a new dysmorphic syndrome. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 240-6 | pmid=5173168 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5173168 }}</ref>
*In 1971, Scott described the association between [[Ligamentous laxity|ligamentous]] laxity which results in hyperextensibility of the fingers, [[genu recurvatum]], flat feet and Aarskog-Scott syndrome (AAS).<ref name="pmid5173168">{{cite journal| author=Scott CI| title=Unusual facies, joint hypermobility, genital anomaly and short stature: a new dysmorphic syndrome. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 240-6 | pmid=5173168 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5173168 }}</ref>
*In 1973, Sugarman et al described an Mexican-American family in which 2 half brothers and their 2 maternal uncles had Aarskog syndrome.
*In 1973, Sugarman et al described an Mexican-American family in which 2 half brothers and their 2 maternal uncles had Aarskog syndrome.
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*In 2005, Orrico et al. described attention deficit-hyperactivity disorder ([[Attention-deficit hyperactivity disorder|ADHD]]) in [[patient]] with Aarskog-Scott syndrome (AAS).<ref name="pmid15809997">{{cite journal| author=Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S et al.| title=Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). | journal=Am J Med Genet A | year= 2005 | volume= 135 | issue= 1 | pages= 99-102 | pmid=15809997 | doi=10.1002/ajmg.a.30700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15809997 }}</ref>
*In 2005, Orrico et al. described attention deficit-hyperactivity disorder ([[Attention-deficit hyperactivity disorder|ADHD]]) in [[patient]] with Aarskog-Scott syndrome (AAS).<ref name="pmid15809997">{{cite journal| author=Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S et al.| title=Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). | journal=Am J Med Genet A | year= 2005 | volume= 135 | issue= 1 | pages= 99-102 | pmid=15809997 | doi=10.1002/ajmg.a.30700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15809997 }}</ref>
*In 2010, Orrico et al. [[genetically]] confirmed 11 patients for Aarskog-Scott syndrome.<ref name="pmid20082460">{{cite journal| author=Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM et al.| title=Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. | journal=Am J Med Genet A | year= 2010 | volume= 152A | issue= 2 | pages= 313-8 | pmid=20082460 | doi=10.1002/ajmg.a.33199 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20082460 }}</ref>
*In 2010, Orrico et al. [[genetically]] confirmed 11 patients for Aarskog-Scott syndrome.<ref name="pmid20082460">{{cite journal| author=Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM et al.| title=Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. | journal=Am J Med Genet A | year= 2010 | volume= 152A | issue= 2 | pages= 313-8 | pmid=20082460 | doi=10.1002/ajmg.a.33199 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20082460 }}</ref>
[[File:FGD1 mutations in Aarskog-Scott syndrome.jpg|alt=Detection of FGD1 mutations|thumb|Detection of ''FGD1'' mutations. (A) Schematic representation of the domains of the ''FGD1'' protein showing mutations (p.Glu380* and p.Gln664*) identified in patients with AAS. Arrows indicate the positions of the mutated nucleotides in ''FGD1''. (B) sequencing results (p.Glu380* and p.Gln664*) detected in exon 5 and 12, respectively. The altered amino acids are shown in red. Case courtesy by Mariana Pérez-Coria et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444161/|title=Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
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== Classification ==
== Classification ==
* There is no established system for the [[classification]] of Aarskog-Scott syndrome (AAS).<ref name="pmid11181572">{{cite journal| author=Estrada L, Caron E, Gorski JL| title=Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. | journal=Hum Mol Genet | year= 2001 | volume= 10 | issue= 5 | pages= 485-95 | pmid=11181572 | doi=10.1093/hmg/10.5.485 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11181572 }}</ref>
* There is no established system for the [[classification]] of Aarskog-Scott syndrome (AAS).<ref name="pmid11181572">{{cite journal| author=Estrada L, Caron E, Gorski JL| title=Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. | journal=Hum Mol Genet | year= 2001 | volume= 10 | issue= 5 | pages= 485-95 | pmid=11181572 | doi=10.1093/hmg/10.5.485 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11181572 }}</ref>
== Pathophysiology ==
== Pathophysiology ==
* Aarskog-Scott syndrome (AAS) is transmitted in [[X-linked recessive]] mode of [[inheritance]].<ref name="pmid7954831">{{cite journal| author=Pasteris NG, Cadle A, Logie LJ, Porteous ME, Schwartz CE, Stevenson RE et al.| title=Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. | journal=Cell | year= 1994 | volume= 79 | issue= 4 | pages= 669-78 | pmid=7954831 | doi=10.1016/0092-8674(94)90552-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7954831 }}</ref><ref name="pmid9268645">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645 }}</ref><ref name="pmid4155960">{{cite journal| author=Aarskog D| title=A familial syndrome of short stature associated with facial dysplasia and genital anomalies. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 235-9 | pmid=4155960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4155960 }}</ref>
* Aarskog-Scott syndrome (AAS) is transmitted in [[X-linked recessive]] mode of [[inheritance]].<ref name="pmid7954831">{{cite journal| author=Pasteris NG, Cadle A, Logie LJ, Porteous ME, Schwartz CE, Stevenson RE et al.| title=Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. | journal=Cell | year= 1994 | volume= 79 | issue= 4 | pages= 669-78 | pmid=7954831 | doi=10.1016/0092-8674(94)90552-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7954831 }}</ref><ref name="pmid9268645">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645 }}</ref><ref name="pmid4155960">{{cite journal| author=Aarskog D| title=A familial syndrome of short stature associated with facial dysplasia and genital anomalies. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 235-9 | pmid=4155960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4155960 }}</ref>
*In some cases Aarskog-Scott syndrome (AAS) is transmitted in [[autosomal dominant]] mode of [[inheritance]].<ref name="pmid63446352">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref><ref name="BawleTyrkus1984">{{cite journal|last1=Bawle|first1=E.|last2=Tyrkus|first2=M.|last3=Lipman|first3=S.|last4=Bozimowski|first4=D.|last5=Opitz|first5=John M.|title=Aarskog syndrome: Full male and female expression associated with an X-autosome translocation|journal=American Journal of Medical Genetics|volume=17|issue=3|year=1984|pages=595–602|issn=0148-7299|doi=10.1002/ajmg.1320170307}}</ref>
*In some cases Aarskog-Scott syndrome (AAS) is transmitted in [[autosomal dominant]] mode of [[inheritance]].<ref name="pmid63446352">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref><ref name="BawleTyrkus1984">{{cite journal|last1=Bawle|first1=E.|last2=Tyrkus|first2=M.|last3=Lipman|first3=S.|last4=Bozimowski|first4=D.|last5=Opitz|first5=John M.|title=Aarskog syndrome: Full male and female expression associated with an X-autosome translocation|journal=American Journal of Medical Genetics|volume=17|issue=3|year=1984|pages=595–602|issn=0148-7299|doi=10.1002/ajmg.1320170307}}</ref>
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*The gene ''[[FGD1]]'' specifically encodes for [[Guanine nucleotide exchange factor|guanine nucleotide]] exchange factor ([[Guanine nucleotide exchange factor|GEF]]).<ref name="pmid14560308">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308 }}</ref>
*The gene ''[[FGD1]]'' specifically encodes for [[Guanine nucleotide exchange factor|guanine nucleotide]] exchange factor ([[Guanine nucleotide exchange factor|GEF]]).<ref name="pmid14560308">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308 }}</ref>
*[[Guanine nucleotide exchange factor]] ([[Guanine nucleotide exchange factor|GEF]]) inturn activates Cdc42 which belongs to Ras homology of the p21 GTPases.<ref name="pmid27199457">{{cite journal| author=Pedigo NG, Van Delden D, Walters L, Farrell CL| title=Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease. | journal=Physiol Genomics | year= 2016 | volume= 48 | issue= 7 | pages= 446-54 | pmid=27199457 | doi=10.1152/physiolgenomics.00101.2015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27199457 }}</ref><ref name="pmid10721717">{{cite journal| author=Pasteris NG, Nagata K, Hall A, Gorski JL| title=Isolation, characterization, and mapping of the mouse Fgd3 gene, a new Faciogenital Dysplasia (FGD1; Aarskog Syndrome) gene homologue. | journal=Gene | year= 2000 | volume= 242 | issue= 1-2 | pages= 237-47 | pmid=10721717 | doi=10.1016/s0378-1119(99)00518-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10721717 }}</ref><ref name="pmid16595546">{{cite journal| author=Rajnicek AM, Foubister LE, McCaig CD| title=Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field. | journal=J Cell Sci | year= 2006 | volume= 119 | issue= Pt 9 | pages= 1723-35 | pmid=16595546 | doi=10.1242/jcs.02896 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16595546 }}</ref>
*[[Guanine nucleotide exchange factor]] ([[Guanine nucleotide exchange factor|GEF]]) inturn activates Cdc42 which belongs to Ras homology of the p21 GTPases.<ref name="pmid27199457">{{cite journal| author=Pedigo NG, Van Delden D, Walters L, Farrell CL| title=Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease. | journal=Physiol Genomics | year= 2016 | volume= 48 | issue= 7 | pages= 446-54 | pmid=27199457 | doi=10.1152/physiolgenomics.00101.2015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27199457 }}</ref><ref name="pmid10721717">{{cite journal| author=Pasteris NG, Nagata K, Hall A, Gorski JL| title=Isolation, characterization, and mapping of the mouse Fgd3 gene, a new Faciogenital Dysplasia (FGD1; Aarskog Syndrome) gene homologue. | journal=Gene | year= 2000 | volume= 242 | issue= 1-2 | pages= 237-47 | pmid=10721717 | doi=10.1016/s0378-1119(99)00518-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10721717 }}</ref><ref name="pmid16595546">{{cite journal| author=Rajnicek AM, Foubister LE, McCaig CD| title=Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field. | journal=J Cell Sci | year= 2006 | volume= 119 | issue= Pt 9 | pages= 1723-35 | pmid=16595546 | doi=10.1242/jcs.02896 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16595546 }}</ref>
*Upon activation of [[CDC42|Cdc42]], [[FGD1]] [[Protein|proteins]] they activate the following:<ref name="pmid10458911">{{cite journal| author=Pasteris NG, Gorski JL| title=Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues. | journal=Genomics | year= 1999 | volume= 60 | issue= 1 | pages= 57-66 | pmid=10458911 | doi=10.1006/geno.1999.5903 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10458911 }}</ref><ref name="pmid10930571">{{cite journal| author=Orrico A, Galli L, Falciani M, Bracci M, Cavaliere ML, Rinaldi MM et al.| title=A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome). | journal=FEBS Lett | year= 2000 | volume= 478 | issue= 3 | pages= 216-20 | pmid=10930571 | doi=10.1016/s0014-5793(00)01857-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10930571 }}</ref><ref name="pmid11093277">{{cite journal| author=Schwartz CE, Gillessen-Kaesbach G, May M, Cappa M, Gorski J, Steindl K et al.| title=Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome. | journal=Eur J Hum Genet | year= 2000 | volume= 8 | issue= 11 | pages= 869-74 | pmid=11093277 | doi=10.1038/sj.ejhg.5200553 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11093277 }}</ref><ref name="pmid92686452">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645 }}</ref><ref name="pmid16246005">{{cite journal| author=Hall A| title=Rho GTPases and the control of cell behaviour. | journal=Biochem Soc Trans | year= 2005 | volume= 33 | issue= Pt 5 | pages= 891-5 | pmid=16246005 | doi=10.1042/BST20050891 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16246005 }}</ref><ref name="pmid10320936">{{cite journal| author=Ridley AJ, Allen WE, Peppelenbosch M, Jones GE| title=Rho family proteins and cell migration. | journal=Biochem Soc Symp | year= 1999 | volume= 65 | issue= | pages= 111-23 | pmid=10320936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10320936 }}</ref><ref name="pmid11509562">{{cite journal| author=Linseman DA, Laessig T, Meintzer MK, McClure M, Barth H, Aktories K et al.| title=An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival. | journal=J Biol Chem | year= 2001 | volume= 276 | issue= 42 | pages= 39123-31 | pmid=11509562 | doi=10.1074/jbc.M103959200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11509562 }}</ref><ref name="pmid10816416">{{cite journal| author=Bishop AL, Hall A| title=Rho GTPases and their effector proteins. | journal=Biochem J | year= 2000 | volume= 348 Pt 2 | issue= | pages= 241-55 | pmid=10816416 | doi= | pmc=1221060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10816416 }}</ref><ref name="OrricoGalli2010">{{cite journal|last1=Orrico|first1=A.|last2=Galli|first2=L.|last3=Faivre|first3=L.|last4=Clayton-Smith|first4=J.|last5=Azzarello-Burri|first5=S.M.|last6=Hertz|first6=J.M.|last7=Jacquemont|first7=S.|last8=Taurisano|first8=R.|last9=Arroyo Carrera|first9=I.|last10=Tarantino|first10=E.|last11=Devriendt|first11=K.|last12=Melis|first12=D.|last13=Thelle|first13=T.|last14=Meinhardt|first14=U.|last15=Sorrentino|first15=V.|title=Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of theFGD1gene|journal=American Journal of Medical Genetics Part A|volume=152A|issue=2|year=2010|pages=313–318|issn=15524825|doi=10.1002/ajmg.a.33199}}</ref>
*Upon activation of [[CDC42|Cdc42]], [[FGD1]] [[Protein|proteins]] they activate the following:<ref name="pmid10458911">{{cite journal| author=Pasteris NG, Gorski JL| title=Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues. | journal=Genomics | year= 1999 | volume= 60 | issue= 1 | pages= 57-66 | pmid=10458911 | doi=10.1006/geno.1999.5903 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10458911 }}</ref><ref name="pmid10930571">{{cite journal| author=Orrico A, Galli L, Falciani M, Bracci M, Cavaliere ML, Rinaldi MM et al.| title=A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome). | journal=FEBS Lett | year= 2000 | volume= 478 | issue= 3 | pages= 216-20 | pmid=10930571 | doi=10.1016/s0014-5793(00)01857-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10930571 }}</ref><ref name="pmid11093277">{{cite journal| author=Schwartz CE, Gillessen-Kaesbach G, May M, Cappa M, Gorski J, Steindl K et al.| title=Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome. | journal=Eur J Hum Genet | year= 2000 | volume= 8 | issue= 11 | pages= 869-74 | pmid=11093277 | doi=10.1038/sj.ejhg.5200553 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11093277 }}</ref><ref name="pmid92686452">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645 }}</ref><ref name="pmid16246005">{{cite journal| author=Hall A| title=Rho GTPases and the control of cell behaviour. | journal=Biochem Soc Trans | year= 2005 | volume= 33 | issue= Pt 5 | pages= 891-5 | pmid=16246005 | doi=10.1042/BST20050891 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16246005 }}</ref><ref name="pmid10320936">{{cite journal| author=Ridley AJ, Allen WE, Peppelenbosch M, Jones GE| title=Rho family proteins and cell migration. | journal=Biochem Soc Symp | year= 1999 | volume= 65 | issue= | pages= 111-23 | pmid=10320936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10320936 }}</ref><ref name="pmid11509562">{{cite journal| author=Linseman DA, Laessig T, Meintzer MK, McClure M, Barth H, Aktories K et al.| title=An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival. | journal=J Biol Chem | year= 2001 | volume= 276 | issue= 42 | pages= 39123-31 | pmid=11509562 | doi=10.1074/jbc.M103959200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11509562 }}</ref><ref name="pmid10816416">{{cite journal| author=Bishop AL, Hall A| title=Rho GTPases and their effector proteins. | journal=Biochem J | year= 2000 | volume= 348 Pt 2 | issue= | pages= 241-55 | pmid=10816416 | doi= | pmc=1221060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10816416 }}</ref><ref name="OrricoGalli2010">{{cite journal|last1=Orrico|first1=A.|last2=Galli|first2=L.|last3=Faivre|first3=L.|last4=Clayton-Smith|first4=J.|last5=Azzarello-Burri|first5=S.M.|last6=Hertz|first6=J.M.|last7=Jacquemont|first7=S.|last8=Taurisano|first8=R.|last9=Arroyo Carrera|first9=I.|last10=Tarantino|first10=E.|last11=Devriendt|first11=K.|last12=Melis|first12=D.|last13=Thelle|first13=T.|last14=Meinhardt|first14=U.|last15=Sorrentino|first15=V.|title=Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of theFGD1gene|journal=American Journal of Medical Genetics Part A|volume=152A|issue=2|year=2010|pages=313–318|issn=15524825|doi=10.1002/ajmg.a.33199}}</ref><ref name="pmid30778386">{{cite journal| author=Egorov M, Polishchuk R| title=Identification of CDC42 Effectors Operating in FGD1-Dependent Trafficking at the Golgi. | journal=Front Cell Dev Biol | year= 2019 | volume= 7 | issue= | pages= 7 | pmid=30778386 | doi=10.3389/fcell.2019.00007 | pmc=6369352 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30778386 }}</ref>
**[[Fibroblasts]]
**[[Fibroblasts]]
**[[Cytoskeletal]] elements which are involved in
**[[Cytoskeletal]] elements which are involved in
Line 45:
Line 44:
***[[Apoptosis]]
***[[Apoptosis]]
***Cellular [[differentiation]]
***Cellular [[differentiation]]
* These abnormalities of [[FGD1]]/[[CDC42|Cdc42]] signaling pathway may produce an defective [[embryonic]] development and abnormal [[Endochondral ossification|endochondral]] and [[Intramembranous ossification|intramembranous]] bone formation and leads to Aarskog-Scott syndrome (AAS).
* These abnormalities of [[FGD1]]/[[CDC42|Cdc42]] signaling pathway may produce an defective [[embryonic]] development and abnormal [[Endochondral ossification|endochondral]] and [[Intramembranous ossification|intramembranous]] bone formation and leads to Aarskog-Scott syndrome (AAS).
== Causes ==
== Causes ==
==== Genetic Cause ====
==== Genetic Cause ====
* Aarskog-Scott syndrome (AAS) is caused by a [[mutation]] in the ''[[FGD1 (gene)|FGD1]]'' gene.
* Aarskog-Scott syndrome (AAS) is caused by a [[mutation]] in the ''[[FGD1 (gene)|FGD1]]'' gene.
== Differentiating Aarskog-Scott syndrome from other Diseases ==
== Differentiating Aarskog-Scott syndrome from other Diseases ==
* Aarskog-Scott syndrome (AAS) must be differentiated from [[Robinow syndrome]], [[Noonan syndrome]], [[pseudohypoparathyroidism]], [[Silver-Russell Syndrome|Silver-Russel]]<nowiki/>l and [[SHORT syndrome|SHORT]] syndrome.<ref name="pmid27544718">{{cite journal| author=Parıltay E, Hazan F, Ataman E, Demir K, Etlik Ö, Özbek E et al.| title=A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel. | journal=J Pediatr Endocrinol Metab | year= 2016 | volume= 29 | issue= 9 | pages= 1111-4 | pmid=27544718 | doi=10.1515/jpem-2015-0482 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27544718 }}</ref><ref name="Weinstein2016">{{cite journal|last1=Weinstein|first1=Lee S.|title=GNAS and McCune-Albright/Fibrous Dysplasia, Albright Hereditary Osteodystrophy, and Pseudohypoparathyroidism|year=2016|pages=1178–1181|doi=10.1093/med/9780199934522.003.0179}}</ref><ref name="Reza JabalameliBriceno20164">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
* Aarskog-Scott syndrome (AAS) must be differentiated from [[Robinow syndrome]], [[Noonan syndrome]], [[pseudohypoparathyroidism]], [[Silver-Russell Syndrome|Silver-Russel]]<nowiki/>l and [[SHORT syndrome|SHORT]] syndrome.<ref name="pmid27544718">{{cite journal| author=Parıltay E, Hazan F, Ataman E, Demir K, Etlik Ö, Özbek E et al.| title=A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel. | journal=J Pediatr Endocrinol Metab | year= 2016 | volume= 29 | issue= 9 | pages= 1111-4 | pmid=27544718 | doi=10.1515/jpem-2015-0482 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27544718 }}</ref><ref name="Weinstein2016">{{cite journal|last1=Weinstein|first1=Lee S.|title=GNAS and McCune-Albright/Fibrous Dysplasia, Albright Hereditary Osteodystrophy, and Pseudohypoparathyroidism|year=2016|pages=1178–1181|doi=10.1093/med/9780199934522.003.0179}}</ref><ref name="Reza JabalameliBriceno20164">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
== Epidemiology and Demographics ==
== Epidemiology and Demographics ==
===Incidence===
===Incidence===
*The [[incidence]] of Aarskog-Scott syndrome (AAS) is unknown.<ref name="Reza JabalameliBriceno20162">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
*The [[incidence]] of Aarskog-Scott syndrome (AAS) is unknown.<ref name="Reza JabalameliBriceno20162">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
*Till now there are 29 cases of Aarskog-Scott syndrome (AAS) had been diagnosed worldwide.
*Till now there are 29 cases of Aarskog-Scott syndrome (AAS) had been diagnosed worldwide.
*The [[prevalence]] of Aarskog-Scott syndrome (AAS) is 1-9 per 1,000,000 in Europe.
*The [[prevalence]] of Aarskog-Scott syndrome (AAS) is 1-9 per 1,000,000 in Europe.
=== Age===
=== Age===
*Aarskog-Scott syndrome (AAS) commonly affects individuals of younger age especially in childwood.
*Aarskog-Scott syndrome (AAS) commonly affects individuals of younger age especially in childwood.
===Race===
===Race===
*There is no [[racial]] predilection to Aarskog-Scott syndrome (AAS).
*There is no [[racial]] predilection to Aarskog-Scott syndrome (AAS).
=== Gender===
=== Gender===
*Aarskog-Scott syndrome (AAS) affects men more commonly than in women.<ref name="Reza JabalameliBriceno2016">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
*Aarskog-Scott syndrome (AAS) affects men more commonly than in women.<ref name="Reza JabalameliBriceno2016">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
== Risk Factors ==
== Risk Factors ==
There are no established [[risk factors]] for Aarskog-Scott syndrome (AAS).
There are no established [[risk factors]] for Aarskog-Scott syndrome (AAS).
== Screening ==
== Screening ==
There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for Aarskog-Scott syndrome (AAS).
There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for Aarskog-Scott syndrome (AAS).
== Natural History, Complications and Prognosis ==
== Natural History, Complications and Prognosis ==
=== Natural History ===
=== Natural History ===
* The [[symptoms]] of Aarskog-Scott syndrome (AAS) usually develop in the first decade of life, and start with symptoms such as delayed [[Growth spurts|growth spurt]].
* The symptoms of Aarskog-Scott syndrome (AAS) usually develop in the first decade of life, and start with symptoms such as delayed [[Growth spurts|growth spurt]].
* The [[symptoms]] of Aarskog-Scott syndrome (AAS) typically develop in 2 to 4 years of age.
* The symptoms of Aarskog-Scott syndrome (AAS) typically develop in 2 to 4 years of age.
=== Complications ===
=== Complications ===
* Common complications of Aarskog-Scott syndrome (AAS) include:<ref name="JogiyaSandy2009">{{cite journal|last1=Jogiya|first1=Aryan|last2=Sandy|first2=Charles|title=Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome|journal=Ophthalmic Genetics|volume=26|issue=3|year=2009|pages=139–141|issn=1381-6810|doi=10.1080/13816810500229025}}</ref><ref name="pmid7953251">{{cite journal| author=Pizio HF, Scott MH, Richard JM| title=Tortuosity of the retinal vessels in Aarskog syndrome (faciogenital dysplasia). | journal=Ophthalmic Genet | year= 1994 | volume= 15 | issue= 1 | pages= 37-40 | pmid=7953251 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7953251 }}</ref><ref name="pmid63446353">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref>
* Common complications of Aarskog-Scott syndrome (AAS) include:<ref name="JogiyaSandy2009">{{cite journal|last1=Jogiya|first1=Aryan|last2=Sandy|first2=Charles|title=Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome|journal=Ophthalmic Genetics|volume=26|issue=3|year=2009|pages=139–141|issn=1381-6810|doi=10.1080/13816810500229025}}</ref><ref name="pmid7953251">{{cite journal| author=Pizio HF, Scott MH, Richard JM| title=Tortuosity of the retinal vessels in Aarskog syndrome (faciogenital dysplasia). | journal=Ophthalmic Genet | year= 1994 | volume= 15 | issue= 1 | pages= 37-40 | pmid=7953251 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7953251 }}</ref><ref name="pmid63446353">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref>
**Cryptorchidism
**[[Cryptorchidism]]
** Spina bifida occulta
**[[Spina bifida occulta]]
** Cervical spine abnormalities
**[[Cervical spine]] abnormalities
**Scoliosis
**[[Scoliosis]]
**Camptodactyly
**[[Camptodactyly]]
**Lymphoedema
**[[Lymphoedema]]
**Optic nerve hypoplasia
**[[Optic nerve]] [[hypoplasia]]
**Retinal vessel tortuosity
**[[Retinal]] vessel [[tortuosity]]
=== Prognosis ===
=== Prognosis ===
*[[Prognosis]] is generally good with Aarskog-Scott syndrome (AAS) patients.
*[[Prognosis]] is generally good with Aarskog-Scott syndrome (AAS) patients.
== Diagnostic study of choice ==
== Diagnostic study of choice ==
* Aarskog-Scott syndrome (AAS) is primarily diagnosed based on clinical presentation based on Teebi criteria which includes:<ref name="pmid28209013">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013 }}</ref><ref name="pmid63446354">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref><ref name="pmid14594174">{{cite journal| author=Darendeliler F, Larsson P, Neyzi O, Price AD, Hagenäs L, Sipilä I et al.| title=Growth hormone treatment in Aarskog syndrome: analysis of the KIGS (Pharmacia International Growth Database) data. | journal=J Pediatr Endocrinol Metab | year= 2003 | volume= 16 | issue= 8 | pages= 1137-42 | pmid=14594174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14594174 }}</ref><ref name="pmid145603082">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308 }}</ref>
* Aarskog-Scott syndrome (AAS) is primarily diagnosed based on clinical presentation based on Teebi criteria which includes:<ref name="pmid63446354">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635 }}</ref><ref name="pmid14594174">{{cite journal| author=Darendeliler F, Larsson P, Neyzi O, Price AD, Hagenäs L, Sipilä I et al.| title=Growth hormone treatment in Aarskog syndrome: analysis of the KIGS (Pharmacia International Growth Database) data. | journal=J Pediatr Endocrinol Metab | year= 2003 | volume= 16 | issue= 8 | pages= 1137-42 | pmid=14594174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14594174 }}</ref><ref name="pmid145603082">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308 }}</ref>
**[[Short stature]]
**[[Short stature]]
**[[Hypertelorism]]
**[[Hypertelorism]]
Line 122:
Line 93:
**Long [[philtrum]]
**Long [[philtrum]]
**Mild facial [[hypoplasia]]
**Mild facial [[hypoplasia]]
*
[[File:Aarskog syndrome.jpg|alt=Aarskog syndrome|thumb|Patients with clinical features of Aarskog syndrome-(A) Patient 1; note distinctive facial characteristics and interdigital tracts in both hands. (B) Patient 2; discrete facial features and the shawl scrotum can be appreciated. (C) Patient 3 and his mother (patient 8); note prominent forehead, widow's peak, hypertelorism, and fold under the lower lip. (D) Patient 4 with widow's peak, midface hypoplasia, ptosis, clinodactyly, and brachydactyly. (E) Patient 5, brother of patient 4, with distinctive facial features, clinodactyly, and brachydactyly. Case courtesy by Mariana Pérez-Coria et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444161/|title=Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
== History and Symptoms ==
== History and Symptoms ==
=== Common Symptoms ===
=== Common Symptoms ===
Common symptoms of Aarskog-Scott syndrome (AAS) include:<ref name="pmid11093277" /><ref name="pmid24637303">{{cite journal| author=Şıklar Z, Berberoğlu M| title=Syndromic disorders with short stature. | journal=J Clin Res Pediatr Endocrinol | year= 2014 | volume= 6 | issue= 1 | pages= 1-8 | pmid=24637303 | doi=10.4274/Jcrpe.1149 | pmc=3986733 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24637303 }}</ref>
Common symptoms of Aarskog-Scott syndrome (AAS) include:<ref name="pmid11093277" /><ref name="pmid24637303">{{cite journal| author=Şıklar Z, Berberoğlu M| title=Syndromic disorders with short stature. | journal=J Clin Res Pediatr Endocrinol | year= 2014 | volume= 6 | issue= 1 | pages= 1-8 | pmid=24637303 | doi=10.4274/Jcrpe.1149 | pmc=3986733 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24637303 }}</ref>
*[[Short stature]] (evident by 1-3 years of age)
*[[Short stature]] (evident by 1-3 years of age)
*[[Mental retardation]]
*[[Mental retardation]]
Line 136:
Line 104:
*[[Hypospadias]]
*[[Hypospadias]]
*Undescended [[testes]]
*Undescended [[testes]]
== Physical Examination ==
== Physical Examination ==
==== HEENT ====
==== HEENT ====
[[Facial]] features are very prominent and important for the diagnosis of Aarskog-Scott syndrome (AAS) which include:<ref name="Reza JabalameliBriceno20163">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref><ref name="pmid19110080">{{cite journal| author=Bedoyan JK, Friez MJ, DuPont B, Ahmad A| title=First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome. | journal=Eur J Med Genet | year= 2009 | volume= 52 | issue= 4 | pages= 262-4 | pmid=19110080 | doi=10.1016/j.ejmg.2008.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19110080 }}</ref><ref name="pmid8322809">{{cite journal| author=Teebi AS, Rucquoi JK, Meyn MS| title=Aarskog syndrome: report of a family with review and discussion of nosology. | journal=Am J Med Genet | year= 1993 | volume= 46 | issue= 5 | pages= 501-9 | pmid=8322809 | doi=10.1002/ajmg.1320460508 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8322809 }}</ref><ref name="UlaşGiampietro2014">{{cite journal|last1=Ulaş|first1=Cıkla|last2=Giampietro|first2=Philip F.|last3=Sadighi|first3=Alireza|last4=Başkaya|first4=Mustafa K.|title=Ruptured Posterior Communicating Artery Aneurysm Associated with Aarskog Syndrome|journal=NMC Case Report Journal|volume=2|issue=3|year=2014|pages=85–87|issn=2188-4226|doi=10.2176/nmccrj.2014-0022}}</ref>
[[Facial]] features are very prominent and important for the diagnosis of Aarskog-Scott syndrome (AAS) which include:<ref name="Reza JabalameliBriceno20163">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref><ref name="pmid19110080">{{cite journal| author=Bedoyan JK, Friez MJ, DuPont B, Ahmad A| title=First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome. | journal=Eur J Med Genet | year= 2009 | volume= 52 | issue= 4 | pages= 262-4 | pmid=19110080 | doi=10.1016/j.ejmg.2008.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19110080 }}</ref><ref name="pmid8322809">{{cite journal| author=Teebi AS, Rucquoi JK, Meyn MS| title=Aarskog syndrome: report of a family with review and discussion of nosology. | journal=Am J Med Genet | year= 1993 | volume= 46 | issue= 5 | pages= 501-9 | pmid=8322809 | doi=10.1002/ajmg.1320460508 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8322809 }}</ref><ref name="UlaşGiampietro2014">{{cite journal|last1=Ulaş|first1=Cıkla|last2=Giampietro|first2=Philip F.|last3=Sadighi|first3=Alireza|last4=Başkaya|first4=Mustafa K.|title=Ruptured Posterior Communicating Artery Aneurysm Associated with Aarskog Syndrome|journal=NMC Case Report Journal|volume=2|issue=3|year=2014|pages=85–87|issn=2188-4226|doi=10.2176/nmccrj.2014-0022}}</ref><ref name="pmid282090132">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013 }}</ref>
* Round face
* Round face
*Facial [[edema]] with downward slanting [[palpebral fissures]]
*Facial [[edema]] with downward slanting [[palpebral fissures]]
*Short [[nose]] along with [[Anteverted nostrils|anteverted]] nares
*Short [[nose]] along with [[Anteverted nostrils|anteverted]] [[nares]]
*Long [[philtrum]]
*Long [[philtrum]]
*Ocular [[hypertelorism]] with [[ptosis]]
*Ocular [[hypertelorism]] with [[ptosis]]
*Maxillary [[hypoplasia]]
*Maxillary [[hypoplasia]]
*A broad upper [[lip]] with a crease below the lower lip
*A broad upper [[lip]] with a crease below the lower [[lip]]
* Mild webbing between the [[Finger|fingers]] and [[Toe|toes]]
*[[Simian crease]]
*[[Simian crease]]
* Broad thumbs and big toes
* Broad [[Thumb|thumbs]] and big [[Toe|toes]]
== Laboratory Findings ==
== Laboratory Findings ==
* There are no [[diagnostic]] laboratory findings associated with Aarskog-Scott syndrome (AAS).
* There are no [[diagnostic]] laboratory findings associated with Aarskog-Scott syndrome (AAS).
== Electrocardiogram ==
== Electrocardiogram ==
* There are no [[The electrocardiogram|ECG]] findings associated with Aarskog-Scott syndrome (AAS).
* There are no [[The electrocardiogram|ECG]] findings associated with Aarskog-Scott syndrome (AAS).
== X-Ray Findings ==
== X-Ray Findings ==
*[[File:Aarskog-Scott syndrome X-ray.jpg|thumb|Scoliosis- a) Early postoperative X-ray (b) 10 years follow-up X-ray.Case courtesy Kerim Sariyilmaz<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634118/|title=Aarskog-Scott syndrome: An unusual cause of scoliosis|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>|alt=Scoliosis]]There are no [[X-rays|x-ray]] findings associated with Aarskog-Scott syndrome (AAS). However, an x-ray may be helpful in the diagnosis of [[complications]] of Aarskog-Scott syndrome (AAS), which include:<ref name="pmid29021683">{{cite journal| author=Sariyilmaz K, Ozkunt O, Korkmaz M, Dikici F, Domanic U| title=Aarskog-Scott syndrome: An unusual cause of scoliosis. | journal=J Craniovertebr Junction Spine | year= 2017 | volume= 8 | issue= 3 | pages= 283-284 | pmid=29021683 | doi=10.4103/jcvjs.JCVJS_133_16 | pmc=5634118 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29021683 }}</ref><ref name="pmid10906777">{{cite journal| author=Gorski JL, Estrada L, Hu C, Liu Z| title=Skeletal-specific expression of Fgd1 during bone formation and skeletal defects in faciogenital dysplasia (FGDY; Aarskog syndrome). | journal=Dev Dyn | year= 2000 | volume= 218 | issue= 4 | pages= 573-86 | pmid=10906777 | doi=10.1002/1097-0177(2000)9999:9999<::AID-DVDY1015>3.0.CO;2-F | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10906777 }}</ref><ref name="pmid282090134">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013 }}</ref>
* There are no [[X-rays|x-ray]] findings associated with Aarskog-Scott syndrome (AAS). However, an x-ray may be helpful in the diagnosis of [[complications]] of Aarskog-Scott syndrome (AAS), which include:<ref name="pmid29021683">{{cite journal| author=Sariyilmaz K, Ozkunt O, Korkmaz M, Dikici F, Domanic U| title=Aarskog-Scott syndrome: An unusual cause of scoliosis. | journal=J Craniovertebr Junction Spine | year= 2017 | volume= 8 | issue= 3 | pages= 283-284 | pmid=29021683 | doi=10.4103/jcvjs.JCVJS_133_16 | pmc=5634118 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29021683 }}</ref>
**[[Skeletal]] abnormalities
**[[Skeletal]] abnormalities
**Tooth abnormalities
**[[Tooth]] abnormalities
**[[Scoliosis]]
**[[Scoliosis]]
== Echocardiography and Ultrasound ==
== Echocardiography and Ultrasound ==
* The [[ultrasound]] can help in detecting the undescended [[testis]] associated with Aarskog-Scott syndrome (AAS).<ref name="pmid22152893">{{cite journal| author=Tasian GE, Copp HL, Baskin LS| title=Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness. | journal=J Pediatr Surg | year= 2011 | volume= 46 | issue= 12 | pages= 2406-13 | pmid=22152893 | doi=10.1016/j.jpedsurg.2011.08.008 | pmc=3712862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22152893 }}</ref>
* The [[ultrasound]] can help in detecting the undescended [[testis]] associated with Aarskog-Scott syndrome (AAS).<ref name="pmid22152893">{{cite journal| author=Tasian GE, Copp HL, Baskin LS| title=Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness. | journal=J Pediatr Surg | year= 2011 | volume= 46 | issue= 12 | pages= 2406-13 | pmid=22152893 | doi=10.1016/j.jpedsurg.2011.08.008 | pmc=3712862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22152893 }}</ref>
== CT-Scan Findings ==
== CT-Scan Findings ==
*[[Head]] [[Computed tomography|CT scan]] may be helpful in the diagnosis of Aarskog-Scott syndrome (AAS). Findings on [[Computed tomography|CT scan]] suggestive Aarskog-Scott syndrome (AAS) include:
* Head [[Computed tomography|CT scan]] may be helpful in the diagnosis of Aarskog-Scott syndrome (AAS). Findings on [[Computed tomography|CT scan]] suggestive Aarskog-Scott syndrome (AAS) include:
**[[Cystic]] development
**[[Cystic]] development
== MRI Findings ==
== MRI Findings ==
* There are no [[Magnetic resonance imaging|MRI]] findings associated with Aarskog-Scott syndrome (AAS).
* There are no [[Magnetic resonance imaging|MRI]] findings associated with Aarskog-Scott syndrome (AAS).
== Medical Therapy ==
== Medical Therapy ==
* There is no treatment for Aarskog-Scott syndrome (AAS); the mainstay of therapy is [[symptomatic]] care.
* There is no treatment for Aarskog-Scott syndrome (AAS); the mainstay of therapy is [[symptomatic]] care.
*Patients with [[short stature]] are treated with [[growth hormone]], which shows promising results in increasing the height of the patients.<ref name="pmid29280742">{{cite journal| author=Deodati A, Cianfarani S| title=The Rationale for Growth Hormone Therapy in Children with Short Stature. | journal=J Clin Res Pediatr Endocrinol | year= 2017 | volume= 9 | issue= Suppl 2 | pages= 23-32 | pmid=29280742 | doi=10.4274/jcrpe.2017.S003 | pmc=5790327 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29280742 }}</ref><ref name="pmid20631818">{{cite journal| author=Frindik JP, Kemp SF| title=Managing idiopathic short stature: role of somatropin (rDNA origin) for injection. | journal=Biologics | year= 2010 | volume= 4 | issue= | pages= 147-55 | pmid=20631818 | doi= | pmc=2898102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20631818 }}</ref>
*Patients with [[short stature]] are treated with [[growth hormone]], which shows promising results in increasing the height of the patients.<ref name="pmid29280742">{{cite journal| author=Deodati A, Cianfarani S| title=The Rationale for Growth Hormone Therapy in Children with Short Stature. | journal=J Clin Res Pediatr Endocrinol | year= 2017 | volume= 9 | issue= Suppl 2 | pages= 23-32 | pmid=29280742 | doi=10.4274/jcrpe.2017.S003 | pmc=5790327 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29280742 }}</ref><ref name="pmid20631818">{{cite journal| author=Frindik JP, Kemp SF| title=Managing idiopathic short stature: role of somatropin (rDNA origin) for injection. | journal=Biologics | year= 2010 | volume= 4 | issue= | pages= 147-55 | pmid=20631818 | doi= | pmc=2898102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20631818 }}</ref>
*
== Interventions ==
== Interventions ==
* There are some recommended [[therapeutic]] interventions for the management of Aarskog-Scott syndrome (AAS), which includes speech [[pathologists]], [[audiologists]] and eye specialists who can improve the quality of the patient's life.
* There are some recommended [[therapeutic]] interventions for the management of Aarskog-Scott syndrome (AAS)., which includes speech [[pathologists]], [[audiologists]] and eye specialists who can improve the quality of the patient's life.
== Surgery ==
== Surgery ==
*[[Surgery]] is usually reserved for patients with [[congenital]] or structural [[malformations]] which involves the following:
*[[Surgery]] is usually reserved for patients with [[congenital]] or structural [[malformations]] which involves the following:
**[[Hypospadias]](opening of the penis is on the underside rather than the tip)
**[[Hypospadias]](opening of the [[penis]] is on the underside rather than the tip)
**[[Inguinal hernia|Inguinal]] or [[umbilical]] [[hernias]]
**[[Inguinal hernia|Inguinal]] or [[umbilical]] [[hernias]]
In 1970, Aarskog-Scott syndrome (AAS) was first described by Aarskog, a Norwegian pediatrician and human geneticist.
In 1971, Scott described the association between ligamentous laxity which results in hyperextensibility of the fingers, genu recurvatum, flat feet and Aarskog-Scott syndrome (AAS).[1]
In 1973, Sugarman et al described an Mexican-American family in which 2 half brothers and their 2 maternal uncles had Aarskog syndrome.
In 1984, Van den Bergh et al. mentioned a patient with Aarskog-Scott syndrome (AAS) development of syndrome of benign intracranial hypertension after minor headtrauma.[5]
In 1994, Fernandez et al. mentioned 10 Japanese patients who are positive with Aarskog syndrome.[6]
In 1998, Logie and Porteous concluded that in patients with Aarskog-Scott syndrome (AAS) have normal intelligence.[7]
In 2002, Lebel et al. is the one who found a missense mutation in the FGD1 gene.[8]
In 2005, Orrico et al. described attention deficit-hyperactivity disorder (ADHD) in patient with Aarskog-Scott syndrome (AAS).[9]
In 2010, Orrico et al. genetically confirmed 11 patients for Aarskog-Scott syndrome.[10]
Detection of FGD1 mutations. (A) Schematic representation of the domains of the FGD1 protein showing mutations (p.Glu380* and p.Gln664*) identified in patients with AAS. Arrows indicate the positions of the mutated nucleotides in FGD1. (B) sequencing results (p.Glu380* and p.Gln664*) detected in exon 5 and 12, respectively. The altered amino acids are shown in red. Case courtesy by Mariana Pérez-Coria et al[11]
Classification
There is no established system for the classification of Aarskog-Scott syndrome (AAS).[12]
These abnormalities of FGD1/Cdc42 signaling pathway may produce an defective embryonic development and abnormal endochondral and intramembranous bone formation and leads to Aarskog-Scott syndrome (AAS).
Causes
Genetic Cause
Aarskog-Scott syndrome (AAS) is caused by a mutation in the FGD1 gene.
Differentiating Aarskog-Scott syndrome from other Diseases
Patients with clinical features of Aarskog syndrome-(A) Patient 1; note distinctive facial characteristics and interdigital tracts in both hands. (B) Patient 2; discrete facial features and the shawl scrotum can be appreciated. (C) Patient 3 and his mother (patient 8); note prominent forehead, widow's peak, hypertelorism, and fold under the lower lip. (D) Patient 4 with widow's peak, midface hypoplasia, ptosis, clinodactyly, and brachydactyly. (E) Patient 5, brother of patient 4, with distinctive facial features, clinodactyly, and brachydactyly. Case courtesy by Mariana Pérez-Coria et al[46]
History and Symptoms
Common Symptoms
Common symptoms of Aarskog-Scott syndrome (AAS) include:[25][47]
There are no diagnostic laboratory findings associated with Aarskog-Scott syndrome (AAS).
Electrocardiogram
There are no ECG findings associated with Aarskog-Scott syndrome (AAS).
X-Ray Findings
Scoliosis- a) Early postoperative X-ray (b) 10 years follow-up X-ray.Case courtesy Kerim Sariyilmaz[54]There are no x-ray findings associated with Aarskog-Scott syndrome (AAS). However, an x-ray may be helpful in the diagnosis of complications of Aarskog-Scott syndrome (AAS), which include:[55][56][57]
There are no MRI findings associated with Aarskog-Scott syndrome (AAS).
Medical Therapy
There is no treatment for Aarskog-Scott syndrome (AAS); the mainstay of therapy is symptomatic care.
Patients with short stature are treated with growth hormone, which shows promising results in increasing the height of the patients.[59][60]
Interventions
There are some recommended therapeutic interventions for the management of Aarskog-Scott syndrome (AAS), which includes speech pathologists, audiologists and eye specialists who can improve the quality of the patient's life.
↑Grier, Robert E.; Farrington, Frank H.; Kendig, Robert; Mamunes, Peter; Opitz, John M. (1983). "Autosomal dominant inheritance of the Aarskog syndrome". American Journal of Medical Genetics. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. ISSN0148-7299.
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