OMIM ID:
Cerebrooculofacioskeletal Syndrome
Alternate Names
Defective Genes
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
Inheritance
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.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.