CCDD Phenotype Associated with a Small Chromosome 2 Deletion.

Area of Science:

• Genetics
• Ophthalmology
• Developmental Biology

Background:

• Congenital cranial dysinnervation disorders (CCDDs) are a group of congenital eye movement abnormalities.
• While several genes are linked to CCDDs, the genetic cause remains unknown for some patients.

Observation:

• A four-year-old girl presented with ptosis, limited ocular motility, and globe retraction.
• Genetic analysis ruled out known CCDD-associated genes.
• Array comparative genomic hybridization identified a de novo deletion in the Xin Actin-binding Repeat containing 2 (XIRP2) gene.

Findings:

• The identified deletion in XIRP2, a gene involved in muscle development, is the first identified chromosomal abnormality affecting only this gene in CCDDs.
• Unlike other CCDD genes impacting neurological development, XIRP2's role is primarily in muscle development and actin filament protection.

Implications:

• This case suggests that genetic factors directly involved in extraocular muscle development and maintenance can cause congenital ocular motility disorders.
• The findings broaden the spectrum of genetic causes for CCDDs, highlighting the importance of muscle-specific genes.