Oculofaciocardiodental syndrome
| Oculofaciocardiodental syndrome |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyed Arash Javadmoosavi, MD[2] Mandana Safakhah, MD[3]
Synonyms and related keywords: MCOPS2 or Microphthalmia, cataracts, radiculomegaly, and septal heart defects or Microphthalmia, syndromic 2, Oculo-facio-cardio-dental syndrome, OFCD syndrome
Overview
Oculofaciocardiodental syndrome (OFCD) is a rare congenital condition affecting eyes, heart, face and teeth. This syndrome is a X-linked syndrome and it has been seen in heterygous female only. Due to its lethal affects on male, there has been no report of affected male. Common signs ad symptoms include cataract, small deep-set eyes, long narrow face, heart defects and teeth with large roots.
Historical Perspective
Oculofaciocardiodental syndrome is very rare; the incidence is estimated to be less than per million people.
- OFCD initially was described by Hayward, an oral surgen, in 1980 as ocular, facial, cardiac and dental abnormalities.[1]
- In 1999, Schulze BR discovered that this syndrome has lethal affects on effected males and it has been seen in only heterozygous females.
- Further investigations by Hayward and Schulze indicated that OFCD has ocular problems like congenital cataract, microphthalmia as well as cardiac symptoms like atrial septal defect, ventricular septal defect and mitral valve prolapse.
- Its dental characteristics including delayed tooth eruption and prolonged retention of primary teeth were described in 1990 by Marashi and Gorlin.
Classification
- There is no stablished system for classification of OFCD.
Pathophysiology
- The genetic analysis in oculofaciocardiodental syndrome patients shows mutations in BCOR gene on chromosome Xp11.4 which has functions like maintaining tissue homeostasis and gene silencing by epigenetic mechanisms.[2]
- BCOR gene provides instructions for making BCL6 corepressor protein. The BCL6 corepressor play an essential role in early embryonic development, including the formation of the eyes and several other tissues and organs like cardiovascular system and face tissues.
- It can also involve in specifying the left and right sides of the body in the developing embryo.
Causes
Differentiating OFCD from other diseases
- It is important to differentiate between OFCD syndrome and marfan syndrome. Patients with marfan syndrome present OFCD symptoms plus musculoskeletal, CNS, pulmonary and integumentary manifestation.[3]
- It can be misrecognized as rubella embryopathy due to association of congenital cataract with cardiac anomalies.
Diagnosis
Diagnosis of oculofaciocardiodental syndrome is based on genetic analysis and its symptoms such as:
Cardiac Abnormalities
- Ventricular septal defect
- Atrial septal defect
- Mild cardiomegaly
- Atrial hypertrophy
- Ventricular hypertrophy
- Benign peripheral pulmonic stenosis
- Mitral valve prolapse
Dental Abnormalities
The specific dental findings (visible on a panoramic radiograph of the jaws) can be easily diagnosed by an orthodontist or a dentist.
- Radiculomegaly: The most consistent and pathognomic dental finding of oculofaciocardiodental syndrome is radiculomegaly (extremely long roots), particularly of the canines and occasionally of other teeth including premolars and incisors.
- Slow and delayed dental eruption: The dental eruption in both the deciduous and the permanent dentition is consistently slow and delayed.
- Oligodontia
- Fused teeth
- Supernumerary teeth
- Malformed permanent teeth
- Enamel defects
- Root dilacerations
- Malposition
- Malocclusion
Facial Abnormalities
- Long narrow face
- High nasal bridge
- Broad nasal tip with separated nasal cartilages
- Laterally curved and thick eyebrows
- Long philtrum
- Clefts of the hard / soft palate
Ocular Abnormalities
- Bilateral congenital cataracts
- Microphthalmia
- Regressive vision impairment
- Secondary glaucoma
- Ptosis
- Exotropia
Others
Some patients may have:
- velopharyngeal insufficiency during speech
- hammer-type flexion of toes 2 and 3
- clinodactyly of toes 4 and 5
Laboratory findings
- There are no diagnostic laboratory findings associated with OFCD
Electrocardiogram
In patients with OFCD, ECG is usually normal, though in patients with VSD, LV hypertrophy can be detected in ECG.
X-ray
Intraoral radiographs in most pf the patients show abnormal dental root maturation with pulp stone-like calcification (PSLC) in teeth pulp and calcified dental papilla (CDP) beneath dental roots.[5]
Cephalometric radiograph in some patients reveals elongated lower facial height and steep mandibular plane angle.[1]. Also abdominal X-ray may show cardiomegaly or pulmonary oedema andplueral effusion in severe cases.
Echocardiography
Echocardiography may be helpful in detection and following up of cardiovascular manifestation of OFCD.
CT scan
Dental Cone Beam CT (CBCT) can be performed in some patients and confirms round-calcified-tissue and PSLC which are associated with radiculomegaly.
MRI
There are a few MRI findings associated with OFCD, though in some cases brain MRI has shown extracranial hemangioma on the frontal scalp.[6]
Management
The OFCD management includes surgical therapies mostly and there is no medical therapy has been confirmed yet.
Surgical therapy
Surgery is the mainstay of treatment for OFCD which includes orthodontic treatment for dental manifestation, orthognathic surgery to solve skeletal anomalies, and cataract surgery. Orthodontic and orthognathic surgery include:[3]
- Lower fixed appliance
- Upper fixed appliance
- Maxillary impaction
- Bilateral sagittal split osteotomy
- Genioplasty
References
- ↑ 1.0 1.1 1.2 1.3 Davoody A, Chen IP, Nanda R, Uribe F, Reichenberger EJ (2012). "Oculofaciocardiodental syndrome: a rare case and review of the literature". Cleft Palate Craniofac J. 49 (5): e55–60. doi:10.1597/10-256. PMC 3354011. PMID 21740180.
- ↑ Hilton, Emma N.; Manson, Forbes D.C.; Urquhart, Jill E.; Johnston, Jennifer J.; Slavotinek, Anne M.; Hedera, Peter; Stattin, Eva-Lena; Nordgren, Ann; Biesecker, Leslie G.; Black, Graeme C.M. (2007). "Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination". Human Molecular Genetics. 16 (14): 1773–1782. doi:10.1093/hmg/ddm125. ISSN 1460-2083.
- ↑ 3.0 3.1 Martinho J, Ferreira H, Paulo S, Paula A, Marto CM, Carrilho E; et al. (2019). "Oculo-Facio-Cardio-Dental Syndrome: A Case Report about a Rare Pathological Condition". Int J Environ Res Public Health. 16 (6). doi:10.3390/ijerph16060928. PMC 6466113. PMID 30875852.
- ↑ Rudrappa S, Kumar R, Kumar GS (2010). "Oculo-facio-cardio-dental syndrome in a girl and her mother". Indian J Hum Genet. 16 (3): 169–71. doi:10.4103/0971-6866.73416. PMC 3009431. PMID 21206708.
- ↑ 5.0 5.1 5.2 Kato J, Kushima K, Kushima F (2018). "New radiological findings and radiculomegaly in oculofaciocardiodental syndrome with a novel BCOR mutation: A case report". Medicine (Baltimore). 97 (49): e13444. doi:10.1097/MD.0000000000013444. PMC 6310535. PMID 30544426.
- ↑ Morgan, T. M.; Colazo, J. M.; Duncan, L.; Hamid, R.; Joos, K. M. (2019). "Two Cases of Oculofaciocardiodental (OFCD) Syndrome due to X-Linked BCOR Mutations Presenting with Infantile Hemangiomas: Phenotypic Overlap with PHACE Syndrome". Case Reports in Genetics. 2019: 1–8. doi:10.1155/2019/9382640. ISSN 2090-6544.