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COFS syndrome

Orpha number ORPHA1466
Synonym(s) Cerebrooculofacioskeletal syndrome
Pena-Shokeir syndrome type 2
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Neonatal/infancy
ICD-10
  • Q87.1
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT
  • 41283003

Summary

Cerebrooculofacioskeletal (COFS) syndrome is a rare genetic disorder, belonging to a family of diseases of DNA repair, characterized by a severe sensorineural involvement.

The exact incidence is unknown. To date, fewer than 20 cases have been confirmed, at a cellular or molecular level, as being truly similar to the primary cases described by Lowry, Pena and Shokeir in the indigenous population of Manitoba.

COFS syndrome constitutes the prenatal extreme form of Cockayne syndrome (see this term). Clinically, the following criteria are found: congenital microcephaly, congenital cataract and/or microphthalmia, arthrogryposis, severe psychomotor developmental delay, height-weight growth delay (principally postnatal) and facial dysmorphism (prominent metopic suture, micrognathism). The axial hypotonia contrasts with the peripheral hypertonia and is associated with feeding difficulties. Cutaneous photosensitivity, peripheral neuropathy, sensorineural hearing loss and pigmentary retinopathy can be observed.

The identified mutations mainly concern the ERCC6/CSB gene. One case has been linked to the ERCC1 gene and particular clinical forms with major photosensitivity have been linked with the ERCC2/XPD and ERCC5/XPG genes. All the genes code for proteins implicated in the same route of DNA repair.

Diagnosis is based on the evidence of a defect in DNA repair (by transcription-coupled nucleotide-excision). This anomaly can be demonstrated on fibroblasts culture by ultraviolet irradiation. Early cerebral imagery is not very specific, but it can reveal cerebral and cerebellar atrophy; myelinization anomalies and calcifications of the basal ganglia can appear secondarily.

Differential diagnoses include infectious fetopathies (cytomegalovirus, rubella, toxoplasmosis; see these terms) and MICRO syndrome (see this term) that can present as clinically similar to COFS syndrome, but with normal DNA repair.

Prenatal diagnosis can be suspected by the presence of cataract, arthrogryposis and microcephaly. It is confirmed by examination of DNA repair in chorionic villi or amniotic cells and by checking for mutations.

COFS syndrome is transmitted in an autosomal recessive manner.

Management is symptomatic. Enteric feeding is often necessary.

COFS syndrome is a severe disease leading to death in the first years of live, particularly by respiratory infections.

Expert reviewer(s)

  • Pr Hélène DOLLFUS
  • Pr Vincent LAUGEL

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