OOM (Old Order Mennonite)

Inheritance: autosomal recessive
Genes: no locus or mutation identified

Chorioretinal dysplasia-microcephaly-mental retardation syndrome

Chorioretinal dysplasia
Mental retardation
Microcephaly
Microcornea
Optic atrophy
Pigmentary retinopathy
Spasticity
Strabismus

Chorioretinopathy With Microcephaly

Clinical Characteristics

General description (for patients):

Children are born with small heads.  The forehead usually slopes steeply and the palate is highly arched.  The onset of walking is often mildly delayed.  The muscles are ‘tight’ and individuals walk with a shuffling gait.  Language remains simple.  Children are usually highly active but interact well with others both at home and at school.  Intelligence levels are below average but individuals are able to carry out everyday tasks.  Degenerative changes are seen in the retina and some children have nystagmus (dancing eyes).  The corneas (windshield of the eye) are small and most individuals are farsighted.  Vision is described as subnormal.

 Medical description: 

Head circumference is usually two standard deviations below normal.  The forehead is steeply sloped but the facial size is normal.  The palate is highly arched.  Deep tendon reflexes are hyperactive and individuals walk with a shuffling gait which is more evident in younger children.  Intelligence quotients are in the 60s.  Speech remains rudimentary.  In spite of this, affected individuals are able to carry out everyday tasks at home.  They are highly social both at home and at school.  Children are often hyperactive.  In spite of mildly abnormal EEGs, only one patient has had seizures.  Cutis marmorata has been reported in several individuals.
This is primarily a pigmentary retinopathy and evidence for choroidal disease is indirect. The retina has variable diffuse or patchy pigmentary changes.  The corneas are small and the optic discs have been described as pale and small.  Hyperopia is present.  At least some patients have nystagmus.  Vision is described as subnormal but no measurements have been reported.  There may be some deterioration of vision as children mature.

Genetics:

Two sibships belonging to conservative Mennonite families in Pennsylvania were reported in the last century.  More recently, another patient in Pennsylvania, related to the original families, was identified.  Exome data from a single individual found a novel mutation, TUBGC6, but its relationship to the disorder awaits confirmation.
  No locus or mutation has been identified but the family pattern and consanguinity of the parents suggest autosomal recessive inheritance.

Treatment:

No effective treatment is known.

Prognosis: 

Lifespan seems to be normal.

Ancillary treatments and support:  

Management is largely supportive.  Physical training may aid mobility.  Refraction with appropriate lens corrections might be helpful for those with higher functioning.

Specialists and specialty centers: 

 

Pediatrician, Ophthalmologist, Neurologist

References:

McKusick, V.A., Stauffer, M., Knox, D.L., and Clark, D.B.:  Chorioretinopathy with hereditary microcephaly.  Arch. Ophthal. 75: 597-600, 1966.  PubMed ID: 5936364

Cantú. J.M., Rojas, J.A., Garcia-Cruz, D., Hernández, A., Pagán P., Fragoso, R., and Manzano, C.:  Autosomal recessive microcephaly associated with chorioretinopathy.  Hum. Genet. 36: 243-247, 1977.  PubMed ID: 870417

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.

Resources:

No available resources at this time