CCDD Phenotype Associated with a Small Chromosome 2 Deletion

Abstract

Purpose: Some individuals are born with congenital limitation of ocular motility, often associated with ptosis and retraction of the globe. Many of these disorders are now known as the congenital cranial dysinnervation disorders (CCDDs). While several genes have been associated with CCDD phenotypes, there are still patients for whom the genetic basis has not been identified. Methods: Clinical evaluation and neuroimaging, sequencing of candidate genes, and array comparative genomic hybridization (array CGH). Results: The patient was a four-year-old girl with mild dysmorphism; bilateral mild ptosis; substantial limitation of abduction OS with milder limitations of abduction OD, adduction OS, and vertical gaze OS; and retraction OS?>?OD on attempted adduction. No mutations were detected in the HOXA1, KIF21A, SALL4, TUBB3, and CHN1 genes. Array CGH revealed a 8 Kb de novo deletion on chromosome 2 (2q24.3) that encompassed a portion of only one gene, the Xin Actin-binding Repeat containing 2 (Gene Symbol XIRP2; NM_001079810). This gene encodes a protein that is involved in muscle development and protecting actin filaments from depolymerization. It interacts functionally with 10 other proteins playing a similar role in muscle development. Conclusions: This patient’s chromosomal abnormality affected only one gene that currently seems involved only in muscle development. All other genes currently associated with the CCDDs affect neurologic development. Genetic information from this patient implies that genes involved in development and maintenance of extraocular muscles can cause congenital ocular motility disorders as well.