OMIM ID:
Cockayne Syndrome, Type B
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The eyes are deep-set. Congenital cataracts are present in 30% of infants. The aggressive course of this form of CS has precluded full delineation of the ocular features but infants have been described with microphthalmos, microcornea and iris hypoplasia.
Systemic Features
Evidence of somatic and neurologic delays is present at birth or shortly thereafter with microcephaly and short stature. Infants never develop normal milestones and may not grow in size beyond that of a 6 month-old child. Communication skills are minimal. They have a progeroid appearance, age rapidly, and most do not live beyond 5 years of age. Feeding problems are common with considerable risk of aspiration, a common cause of respiratory infections and early death. Severe flexion contractures develop early and may interfere with motor function. Tremors and weakness contribute as well. The skin is sensitive to UV radiation in some but not all patients. However, the frequency of skin cancer is not increased. Endogenous temperature regulation may be a problem.
At least some cases with what has been called cerebro-oculo-facio-skeletal syndrome have been genotypically documented to have type B CS, the severe form of Cockayne syndrome.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from mutations in ERCC6 (10q11) rendering the excision-repair cross-complementing protein ineffective in correcting defects during DNA replication. Mutations in this gene account for about 75% of CS patients. However, using date of onset and clinical severity, type A CS (216400) disease is far more common even though the ERCC8 mutations are found in only 25% of individuals. Type A CS (216400) also has a somewhat later onset and is less severe in early stages.
Type III (216411) is poorly defined but seems to have a considerably later onset and milder disease. The mutation is type III is unknown.
Some patients have combined phenotypical features of cerebrooculofacioskeletal syndrome (214150) and xeroderma pigmentosum (XP) known as the XP-CS complex (216400). Defective DNA repair resulting from mutations in excision-repair cross-complementing or ERCC genes is common to both disorders. Two complementation groups have been identified in CS and seven in XP. XP patients with CS features fall into only three (B, D, G) of the XP groups. XP-CS patients have extreme skin photosensitivity and a huge increase in skin cancers of all types. They also have an increase in nervous system neoplasms.
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.