Cerebro-oculo-facio-skeletal syndrome

Joseph R Siebert PhD (Dr. Siebert of the University of Washington has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released January 21, 1998; last updated June 4, 2017; expires June 4, 2020

This article includes discussion of cerebro-oculo-facio-skeletal syndrome, cataracts-microcephaly-kyphosis-limited joint movement, COFS, and Pena-Shokeir II syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

In this article, the author updates information on cerebro-oculo-facio-skeletal (COFS) syndrome. The condition is rare, with autosomal recessive inheritance, and manifests abnormal facies, ocular changes (eg, cataracts, retinal degeneration, microcornea, optic atrophy), in utero and postnatal growth retardation, severe psychomotor retardation, cerebral and cerebellar degeneration with calcification in basal ganglia and white matter, progressive joint contractures and wasting, and death in infancy or early childhood. In many instances, the disorder results from a mutation in the Cockayne syndrome group B (ERCC6/CSB) gene or xeroderma pigmentosum (ie, DNA repair) genes (ERCC2/XPD, ERCC5/XPG, ERCC1/XPF, or ERCC4), mirroring phenotypic and clinical similarities between these conditions.

Key points

 

• Cerebro-oculo-facio-skeletal syndrome is rare, with autosomal recessive inheritance, and manifests abnormal facies, ocular changes (eg, cataracts, retinal degeneration, microcornea, optic atrophy), in utero and postnatal growth retardation, severe psychomotor retardation, microcephaly with cerebral and cerebellar degeneration and calcification in basal ganglia and white matter, arthrogryposis with progressive joint contractures and wasting, and death in infancy or early childhood.

 

• The disorder results from a mutation in 1 of a number of genes, to date the Cockayne syndrome group B (ERCC6/CSB) gene or xeroderma pigmentosum (DNA repair) genes (ERCC2/XPD, ERCC5/XPG, ERCC1/XPF), reflecting phenotypic and clinical similarities between these conditions.

Historical note and terminology

Cerebro-oculo-facio-skeletal syndrome was first described by Pena and Shokeir in 1974. They identified 10 children, 9 of whom were from 2 families of North American aboriginal background residing in or near the province of Manitoba, Canada, with a uniform constellation of congenital abnormalities. On the basis of the apparent heredity and affected systems they entitled their paper “Autosomal recessive cerebro-oculo-facio-skeletal syndrome” (Pena and Shokeir 1974). This designation has been generally accepted. Since then, numerous case reports have dealt largely with clinical aspects of the disorder and its possible relationship to other disorders. A search for the molecular pathogenesis of the disorder advanced significantly in 1996, when XPF was cloned (Gregg et al 2011). The ERCC (excision repair cross complementation) and XP (xeroderma pigmentosum) genes function as complexes that are essential to the repair of DNA (damaged by ultraviolet light, carcinogens, or mutagens) and, hence, are shown together in texts (Kirschner and Melton 2010; Fagbemi et al 2011).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.