NeurometPlus

Incidence

COFS syndrome is inherited as an autosomal recessive genetic trait. Cerebro-oculo-facio-skeletal syndrome is very rare, with roughly 50 cases reported in the medical literature. The largest number of affected families have been among North American aboriginal populations of central Canada. Cases have also been reported in the United States (in both mixed-European and Afro-American backgrounds), Mexico, Finland, Italy, Egypt, Arabic countries, and Japan.

Clinical Characteristics

Cerebrooculofacioskeletal (COFS) syndrome is a rare genetic degenerative disorder of prenatal onset, affecting the brain, eye and spinal cord. After birth, it t leads rapidly, i.e. within a few weeks, to cerebral atrophy, hypoplasia of the corpus callosum, hypotonia and even areflexia severe mental retardation, cataracts, optic atrophy, progressive and multiple joint contractures, and growth deficiency. Reflexes are diminished or absent. Facial dysmorphism is constant: microcephaly, prominent nasal root with long philtrum, micrognathism, and upper lip overhanging the lower one. Abnormalities of the skull, eyes, limbs, heart and kidney also occur. Generally, patients die in the first year of life. Transmission of COFS syndrome is autosomal recessive. Two genes are involved in this disorder: ERCC6 and ERCC2. No molecular diagnosis is currently available. It is considered by some authors as a severe allelic form of Cocayne syndrome. Medical support consists in physiotherapy and intensive care. In summary, Cerebro-oculo-facio-skeletal (COFS) syndrome is a genetic degenerative disorder of the brain and spinal cord that begins before birth. The disorder is characterized by growth failure at birth and little or no neurological development, structural abnormalities of the eye and fixed bending of the spine and joints. Abnormalities of the skull, face, limbs and other parts of the body may also occur. COFS syndrome is inherited as an autosomal recessive genetic trait. COFS is now considered to be part of the spectrum of disorders within Cockayne syndrome. Affected individuals exhibit degeneration of brain and bone beginning before birth, and generalized progressive wasting after birth. These features suggest that cerebro-oculo-facio-skeletal syndrome is a primary degenerative disorder affecting many cell types. The neuropathological changes and other phenotypic features are almost identical to those described in early-onset Cockayne syndrome.

Precipitants

None

Provocation Tests

None

Diagnostic Procedures

Currently, the diagnosis of cerebro-oculo-facio-skeletal syndrome is made on the basis of accurate phenotypic description with the addition of skeletal survey and neuroradiologic work-up. Skin biopsy for fibroblast culture to assess ultraviolet sensitivity. The appearance of those affected by the disorder is relatively characteristic and includes the major diagnostic criteria of (1) microcephaly; (2) ocular anomalies including cataracts, microphthalmia, and blepharophimosis. (3) dysmorphic facies with a high and broad nasal bridge, large ears, overhanging upper lip, and micrognathia; and (4) musculo-skeletal abnormalities including flexion contractures of the limbs, scoliosis, hip dysplasia or dislocation, narrow pelvis, short stature, osteoporosis, dysplastic acetabula, and rocker-bottom feet with proximal displacement of the second metatarsals and longitudinal grooves in the soles along the second metatarsal. Infants may also have a short neck, hirsutism, widely spaced nipples, simian creases, hypotonia, and renal anomalies. Affected children are usually small at birth due to intrauterine growth retardation.