Nucleotide excision repair; NER; disorders of cellular DNA repair; photosensitivity; MICRO syndrome;
COFS syndrome
Keywords This section has been translated automatically.
Definition This section has been translated automatically.
COFS syndrome (COFS stands for Cerebro-Oculo-Facio-Skeletal Syndrome) represents the clinically most severe, prenatal end of the Cockayne syndrome spectrum. It is an extremely rare, autosomal-recessive neurodegenerative disorder that is genetically classified as a defect in nucleotide excision repair (NER)—that is, a disorder of cellular DNA repair.
Etiopathogenesis This section has been translated automatically.
The syndrome is classified as part of the spectrum of inherited defects in nucleotide excision repair (NER). Clinically, marked photosensitivity is evident (Suzumura H et al. 2010).
In COFS syndrome, as in Cockayne syndrome, DNA repair is impaired in the transcription-coupled NER pathway, but not in the global genome-wide NER pathway (see Cockayne syndrome). All mutations have been found in the Cockayne syndrome gene (CSB), in the xeroderma pigmentosum genes (XPD and XPG), and in the ERCC1 gene, which is involved in the transcription-coupled NER pathway.
Clinic This section has been translated automatically.
The syndrome begins in utero (prenatally) and is characterized by a combination of neurological, ocular, facial, and skeletal malformations. Notable features include characteristic facial traits such as a prominent nasal bridge, an extremely small lower jaw (micrognathia), and low-set ears
Brain and Nervous System: Pronounced microcephaly (abnormally small head), progressive loss of brain tissue (brain atrophy), severe psychomotor developmental delay, and pronounced muscular hypotonia (weakness) of the trunk with concurrent spasticity of the extremities.
Eyes: Cataracts present at birth (congenital cataracts), abnormally small eyes (microphthalmia), and optic nerve atrophy.
Literature This section has been translated automatically.
- Graham JM Jr et al. (2004) MICRO syndrome: an entity distinct from COFS syndrome. Am J Med Genet A. 128A:235-245.
- Derbent M et al. (2004) Congenital cataract, microphthalmia, hypoplasia of the corpus callosum, and hypogenitalism: a report and review of MICRO syndrome. Am J Med Genet A 128A:232–234.
- Kosuga M et al. (2000) Cerebro-oculo-facio-skeletal (COFS) syndrome. Ryoikibetsu Shokogun Shirizu. 2000:49–50.
- Suzumura H et al. (2010) Cerebro-oculo-facio-skeletal syndrome. Adv Exp Med Biol 685:210-214.