Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations

Khaled K. Abu-Amero, Flavio Faletra, Paolo Gasparini, Fulvio Parentin, Stefano Pensiero, Ibrahim A. Alorainy, Ali M. Hellani, Dario Catalano, Thomas M. Bosley

Research output: Contribution to journalArticle

Abstract

Background: To describe clinical and genetic observations in a patient with horizontal gaze palsy and progressive scoliosis (HGPPS) without identified mutations in the ROBO3 gene. Materials and Methods: Neurologic and orthopedic evaluation of the proband; sequencing all exons, exon-intron boundaries, and promoter region of ROBO3 in the proband and his mother. Array CGH was also carried out in the proband and his mother to evaluate possible chromosomal deletion(s) and/or duplication(s). Results: The proband had complete horizontal gaze restriction with full vertical gaze and small amplitude horizontal pendular nystagmus. He also had severe scoliosis and brainstem hypoplasia pathognomonic of HGPPS. However, complete sequencing of ROBO3 twice in both forward and reverse directions did not reveal any mutations. Array CGH investigation revealed no chromosomal abnormalities. Conclusions: This patient had clinical and neuroimaging characteristics considered pathognomonic of HGPPS and yet did not have ROBO3 mutations. A clinical misdiagnosis is unlikely in the absence of facial weakness (typical of Moebius syndrome), deafness (typical of the HOXA1 spectrum), or mental retardation (typical of other central decussation abnormalities). It is perhaps more likely that a phenotype identical to HGPPS can be caused by abnormalities in ROBO3 splice variant expression, by mutations of a gene other than ROBO3, or by some environmental or epigenetic factor(s) inhibiting the action of ROBO3 or its protein product in the developing brainstem.

Original languageEnglish
Pages (from-to)212-216
Number of pages5
JournalOphthalmic Genetics
Volume32
Issue number4
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • horizontal gaze palsy and progressive scoliosis
  • ROBO3 gene
  • scoliosis

ASJC Scopus subject areas

  • Ophthalmology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)

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