Microphthalmia, Syndromic 2

What is Microphthalmia, Syndromic 2?

It is a rare genetic syndrome also known as Marashi-Gorlin or OFCD syndrome. The syndrome presents with multiple congenital abnormalities that affect the face, dental and heart. It also includes eye abnormalities.

This syndrome is also known as:
Anop2, Formerly Maa2, Formerly Microphthalmia, Cataracts, Radiculomegaly, And Septal Heart Defects Oculo-Facio-Cardio-Dental (OFCD) syndrome Oculofaciocardiodental Syndrome OFCD Ofcd Syndrome Wilkie (1993) - cataract; microphthalmia; septal defects

What gene changes cause Microphthalmia, Syndromic 2?

Mutations to the BCOR gene are responsible for the syndrome. The syndrome is inherited in an X-linked dominant pattern.

In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.

What are the main symptoms of Microphthalmia, Syndromic 2?

The main symptoms of the syndrome include the following:

Eye anomalies: cataracts present at birth, secondary glaucoma and very small eyes, in some cases the ocular tissue is missing completely and in some cases these anomalies can contribute to vision loss
Facial features and abnormalities: a long and narrow face, high nasal bridge, pointed nose with a cleft or divide at the end of it and a cleft palate
Heart and cardiac defects: atrial septal defect, ventricular septal defect, floppy mitral valve
Dental issues: delayed eruption of secondary teeth, primary teeth that are delayed in falling out, teeth with enlarged roots

Possible clinical traits/features:
Flexion contracture, Cryptorchidism, Decreased body weight, Cubitus valgus, Microcornea, Ectopia lentis, Double outlet right ventricle, Retinal detachment, Developmental cataract, Clinodactyly of the 5th finger, Anophthalmia, Dental malocclusion, Delayed eruption of teeth, Motor delay, Dextrocardia, Feeding difficulties in infancy, Exotropia, X-linked dominant inheritance, Pulmonic stenosis, Umbilical hernia, Ventricular septal defect, Reduced number of teeth, Thick eyebrow, Ptosis, Microcephaly, Talipes equinovarus, Scoliosis, Spastic paraparesis, Radioulnar synostosis, Single median maxillary incisor, Abnormal cardiac septum morphology, Abnormal mitral valve morphology, Abnormal pulmonary valve morphology, Asymmetry of the ears, Aplasia/Hypoplasia affecting the eye, Aortic valve stenosis, Aplasia/Hypoplasia of the thumb, Cleft palate, Atrial septal defect, Blepharophimosis, Bifid uvula, Cataract, Camptodactyly of toe, Broad nasal tip, Bifid nasal tip, Highly arched eyebrow, Prominent nasal bridge, Fused teeth

How does someone get tested for Microphthalmia, Syndromic 2?

The initial testing for Microphthalmia, Syndromic 2 can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Microphthalmia, Syndromic 2

Wilkie et al., (1993) reported a mother and daughter with eye abnormalities, heart defects, and an unusual face. The mother had microphthalmia and had bilateral cataracts from childhood. The daughter had shallow anterior chambers, bilateral posterior embryotoxon, posterior cataracts, and a hyperplastic primary vitreous. The mother had a repaired ASD and the daughter had a large secundum ASD and a large perimembranous VSD. In the mother there was bilateral ptosis with downslanting palpebral fissures. The nose was prominent but narrow, and there was notching of the alae nasi. She had required treatment for persisting deciduous dentition and unerupted teeth. The crowns and roots of several incisors and canines were unusually large. Additional findings in the daughter were a midline bony cleft of the upper gum, 2-3 syndactyly of the toes bilaterally, and an anteriorly placed anus. Molecular deletions of 22q11 could not be demonstrated.
Aalfs et al., (1996) reported two unrelated patients with similar features. The dental anomalies consisted of persistent primary teeth, delayed eruption of secondary teeth, absent teeth, variable root length, radiculomegaly, and peg shaped incisors. One patient had a transverse vaginal septum and the other a cleft palate. Both were of normal intelligence. The dental findings were well reviewed by Oberoi et al., (2005)
Marashi and Gorlin (1990) reported a 20-year-old woman with radiculomegaly of the canine teeth who had been treated for congenital cataracts. Her brother had similar tooth anomalies but no cataracts. Other isolated cases were reviewed. Gorlin et al., (1996) suggest that these cases have the same condition as those described above. They reported a further two cases. In one the parents were first cousins and in the other there was moderate mental retardation. Because all seven cases reported to that date had been female X-linked dominant inheritance was suggested. Obwegeser and Gorlin (1997) publish photographs and more details about a case reported in the Gorlin et al., (1996) paper. Schulze et al., (1999) report three further cases and provide a good review.
Hedera and Gorski (2003) reported an affected mother and daughter. Both had skewed X-inactivation supporting X-linked dominant inheritance. The daughter had in addition intestinal malrotation and hypoplastic thumbs.
Mutations have now been found (Ng et al., 2004), in BCOR (at Xp11). Further mutations were reported by Oberoi et al., (2005) and Horn et al., (2005). These latter authors looked for mutations in 8 patients with Lenz microphthalmia, but found none. McGovern et al., (2006) reported a mother and child with this condition. The dental findings were emphasized.
Hilton et al., (2007), found laterality defects (dextrocardia, intestinal malrotation, asplenia) in 3 patients and suggest that BCOR plays an important role in vertebrate laterality. Mosaicism for the BCOR mutation was found by Hilton et al., (2009) in 2 females.
Danda et al., (2014) reported 2 sisters with indirect evidence of mosaicism in one of their parents.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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