Cerebrooculofacioskeletal Syndrome

Clinical Characteristics
Ocular Features: 

Congenital cataracts and microphthalmia are frequent findings in this disorder.  Delayed mental development and early death in childhood have limited full delineation of the ocular phenotype.  Photosensitivity, nystagmus, optic nerve atrophy, and pigmentary retinopathy have been reported.  The eyes may appear deeply-set.

Systemic Features: 

Microcephaly, flexion contractures, prominent nasal root and an overhanging upper lip are common features.  Severe developmental and growth delays are evident early followed by progressive behavioral and intellectual deterioration.  Both hypotonia and hyperreflexia have been described.    Kyphosis and scoliosis are common.  CT scans may show intracranial calcifications and brain histology shows severe neurodegeneration with neuronal loss and gliosis.  Respiratory distress may also occur and some individuals have died in the first decade of life.

Genetics

Homozygous mutations in the ERCC6 gene (10q11) seem to be responsible for this autosomal recessive disorder.  Several sets of parents have been consanguineous.  Mutations in the same gene are responsible for Cockayne type B syndrome (133540) and some suggest that the variable phenotype represents a spectrum of disease rather than individual entities. Cerebrooculofacioskeletal syndrome represents the more severe phenotype in this spectrum.

Treatment
Treatment Options: 

No treatment is available for this disorder.

References
Article Title: 

References

Jonas JB, Mayer U, Budde WM. Ocular findings in cerebro-oculo-facial-skeletalsyndrome (Pena-Shokeir-II syndrome). Eur J Ophthalmol. 2003 Mar;13(2):209-211.

PubMedID: 28252747

Meira LB, Graham JM Jr, Greenberg CR, Busch DB, Doughty AT, Ziffer DW, Coleman DM, Savre-Train I, Friedberg EC. Manitoba aboriginal kindred with original cerebro-oculo- facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene. Am J Hum Genet. 2000 Apr;66(4):1221-8.

PubMedID: 10739753

Del Bigio MR, Greenberg CR, Rorke LB, Schnur R, McDonald-McGinn DM, Zackai EH. Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome. J Neuropathol Exp Neurol. 1997 Oct;56(10):1147-57.

PubMedID: 9329459