chorioretinal dysplasia-microcephaly-mental retardation syndrome

Chorioretinopathy with Microcephaly 1

Clinical Characteristics
Ocular Features: 

The ocular features have not been well described.  Small corneas, hyperopia, pale optic nerves and a variety of pigmentary changes in the retina have been reported.  The latter may consist of diffuse, fine or granular pigmentary changes.  Areas of pigmentary atrophy are often associated with patchy areas of pigmentary clumping.  These changes are usually located posterior to the equator.  Choroidal vessels may be sparse where the RPE is absent.  It has been suggested that the patchy pattern of retinal pigmentation resembles ocular toxoplasmosis.  Strabismus is common.  One report suggests microphthalmos in a patient.  Vision has been reported as subnormal from the first year of life but no quantitative data are available.

Systemic Features: 

Microcephaly is a consistent feature.  The forehead is steeply sloped but facial size appears normal.  The palate is highly arched.  Patients often have hyperactive deep tendon reflexes and walk with a shuffling gait.  Children are often hyperactive and highly social.  Intelligence quotients are usually subnormal. No lymphedema has been reported.  At least some patients have cutis marmorata.

On MRI diffuse pachygryria is seen.  The vermis is hypoplastic and the surface area of the corpus callosum is reduced to half of normal. 

Genetics

 Parental consanguinity was present in two reported families and pedigrees are consistent with autosomal recessive inheritance with homozygous mutations of TUBGCP6 (22p22) responsible.

This presumed recessive disorder appears to be different than the autosomal dominant disorder of lymphedema, microcephaly, and chorioretinal dysplasia  (MCLMR) (152950) although molecular confirmation is lacking.

For somewhat similar disorder see Chorioretinopathy with Microcephaly 2 (616171).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is supportive.

References
Article Title: 

Genetic mapping and exome sequencing identify variants associated with five novel diseases

Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. Epub 2012 Jan 17. PubMed PMID: 22279524.

PubMed ID: 
22279524

Chorioretinal dysplasia, microcephaly, and mental retardation

Clinical Characteristics
Ocular Features: 

The ocular phenotype has not been well defined in this condition since few families have been reported.  Microphthalmia is present in some patients.  The corneas may be small and there is often some conjunctival growth over the limbus.

The retinal features consist of lacunar depigmentation of the RPE and in some cases resemble the lesions of congenital toxoplasmosis.  Eighty to 90 per cent of patients have areas of atrophic and dysplastic-appearing lesions of the retina and choroid with vascular attenuation.  The edges of lacunae may have patchy hyperpigmentation.  These lesions are usually static but may show mild progression.  Visual acuity is generally stable or only mildly progressive.  However, other patients have a severe reduction in acuity.  ERG responses are reduced.

Systemic Features: 

The amount of microcephaly may be minimal and at least some patients have 'bulging' foreheads.  The amount of mental deficiency varies from mild to severe.  IQ levels are generally in the range of 60-70.   Hypotonia has been reported in more severe cases.  Skull size is usually 2-3 standard deviations below the mean and generally has some frontal prominence.

Genetics

This seems to be an autosomal dominant disorder although no loci or mutations have been identified.  It is likely that the category of disease known as microphthalmia-chorioretinal syndrome consists of a heterogeneous group of disorders.  No locus or specific mutation has been identified.

It differs from the microcephaly, lymphedema, chorioretinopathy syndrome (152950) in which retinal folds, ptosis and lymphedema are associated with a typical facial phenotype.  For other disorders in this database having a somewhat similar phenotype see: chorioretinopahty and microcephaly type 1 (251270) and type 2 (616171).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment is supportive.  Low vision aids may be helpful.

References
Article Title: 
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