Background: Duane retraction syndrome (DRS) is the most common of the congenital cranial dysinnervation disorders (CCDDs). CCDDs can be monogenic or chromosomal in origin. Identification of the genetic cause(s) in patients and families with DRS facilitates definitive diagnosis and provides insights into these developmental errors.
Materials and methods: This study described a young girl with DRS on the left and several additional developmental abnormalities. Clinical examination including neuroimaging, sequencing of candidate genes associated with DRS, and array comparative genomic hybridization (array CGH) were performed.
Results: The proband had unilateral DRS type 3 on the left with somewhat low-set ears, mild motor delay with normal intelligence, and an asymmetric neck without a palpable right sternocleidomastoid muscle. Spine X-rays revealed a Klippel-Feil syndrome (KFS) and an MRI showed a webbed neck. She also had spina bifida at C8-T1 and a submucosal cleft palate. The parents of the proband were related with no other family member affected similarly. Sequencing of SALL4, CHN1, HOXA1, and TUBB3 did not show any mutation. Array CGH revealed de novo deletions of 21 Kb on chromosome 12q24.31 and 11 Kb on chromosome 22q13.31, each encompassing only one gene, ring finger protein 34, E3 ubiquitin protein ligase (RNF34) and peroxisome proliferator-activated receptor alpha (PPARA) respectively.
Conclusions: This patient presents an unusual phenotype associated with a unique combination of two chromosomal microdeletions.
Keywords: Array CGH; Duane retraction syndrome; Klippel-Feil anomaly; cleft palate; congenital cranial dysinnervation disorder; dysmorphism; spina bifida.