CCDD Phenotype Associated with a Small Chromosome 2 Deletion.
OBJECTIVE
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.
a Department of Ophthalmology , College of Medicine, King Saud University , Riyadh , Saudi Arabia .|b Department of Ophthalmology , College of Medicine, University of Florida , Jacksonville , Florida , USA .
Khaled K
KK
Abu-Amero
a Department of Ophthalmology , College of Medicine, King Saud University , Riyadh , Saudi Arabia .
Thomas M
TM
Bosley
a Department of Ophthalmology , College of Medicine, King Saud University , Riyadh , Saudi Arabia .
Altaf A
AA
Kondkar
a Department of Ophthalmology , College of Medicine, King Saud University , Riyadh , Saudi Arabia .|c Division of Ophthalmology, Faculty of Health Sciences , University of Stellenbosch , Tygerberg , South Africa , and.
Darren T
DT
Oystreck
d Division of Pediatric Ophthalmology , King Khaled Eye Specialist Hospital , Riyadh , Saudi Arabia.
Arif O
AO
Khan
D001763:Blepharoptosis / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003391:Cranial Nerves / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004370:Duane Retraction Syndrome / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D009801:Oculomotor Muscles / Q000294:innervation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; C500306:XIRP2 protein, human
Congenital cranial dysinnervation disorder; Duane retraction syndrome; XIRP2; dysmorphism; ptosis