Muscle involvement in the cerebro-oculo-facio-skeletal syndrome

Area of Science:

• Genetics and rare diseases
• Neurology
• Ophthalmology

Background:

• Cerebro-oculo-facio-skeletal syndrome (COFS) is a rare autosomal recessive disorder.
• Typically characterized by severe developmental delays, microcephaly, and distinctive facial and skeletal abnormalities.
• Ultraviolet sensitivity is a reported, but not universal, feature.

Observation:

• A 14-year-old male with consanguineous parents presented with microcephaly, intracranial calcifications, severe intellectual disability, cataracts, optic atrophy, pigmentary retinopathy, contractures, scoliosis, and failure to thrive.
• Brain imaging showed extensive basal ganglia calcifications.
• The patient exhibited severe muscle weakness with end-stage muscle changes on biopsy, but had normal ultraviolet sensitivity.

Findings:

• The patient's phenotype aligns with cerebro-oculo-facio-skeletal syndrome (COFS).
• This report details significant muscle involvement in a COFS patient with normal ultraviolet sensitivity.
• This is the first documented instance of severe muscle weakness in a COFS patient lacking abnormal ultraviolet sensitivity.

Implications:

• This case expands the known phenotypic spectrum of COFS, demonstrating overlap between patients with and without abnormal ultraviolet sensitivity.
• It emphasizes the importance of considering COFS in the differential diagnosis of congenital muscular dystrophies.
• Highlights the need for further research into the genetic and molecular underpinnings of muscle involvement in COFS.