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 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 (US)
Pages (from-to)212-216
Number of pages5
JournalOphthalmic Genetics
Volume32
Issue number4
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Scoliosis
Paralysis
Pathologic Nystagmus
Mutation
Brain Stem
Exons
Mobius Syndrome
Mothers
Deafness
Diagnostic Errors
Genetic Promoter Regions
Epigenomics
Neuroimaging
Chromosome Aberrations
Intellectual Disability
Introns
Nervous System
Genes
Orthopedics
Phenotype

Keywords

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

ASJC Scopus subject areas

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

Cite this

Abu-Amero, K. K., Faletra, F., Gasparini, P., Parentin, F., Pensiero, S., Alorainy, I. A., ... Bosley, T. (2011). Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations. Ophthalmic Genetics, 32(4), 212-216. https://doi.org/10.3109/13816810.2011.574186

Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations. / Abu-Amero, Khaled K.; Faletra, Flavio; Gasparini, Paolo; Parentin, Fulvio; Pensiero, Stefano; Alorainy, Ibrahim A.; Hellani, Ali M.; Catalano, Dario; Bosley, Thomas.

In: Ophthalmic Genetics, Vol. 32, No. 4, 11.2011, p. 212-216.

Research output: Contribution to journalArticle

Abu-Amero, KK, Faletra, F, Gasparini, P, Parentin, F, Pensiero, S, Alorainy, IA, Hellani, AM, Catalano, D & Bosley, T 2011, 'Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations', Ophthalmic Genetics, vol. 32, no. 4, pp. 212-216. https://doi.org/10.3109/13816810.2011.574186
Abu-Amero KK, Faletra F, Gasparini P, Parentin F, Pensiero S, Alorainy IA et al. Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations. Ophthalmic Genetics. 2011 Nov;32(4):212-216. https://doi.org/10.3109/13816810.2011.574186
Abu-Amero, Khaled K. ; Faletra, Flavio ; Gasparini, Paolo ; Parentin, Fulvio ; Pensiero, Stefano ; Alorainy, Ibrahim A. ; Hellani, Ali M. ; Catalano, Dario ; Bosley, Thomas. / Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations. In: Ophthalmic Genetics. 2011 ; Vol. 32, No. 4. pp. 212-216.
@article{aa647fd6d93c4f638e56c76357237cab,
title = "Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations",
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.",
keywords = "horizontal gaze palsy and progressive scoliosis, ROBO3 gene, scoliosis",
author = "Abu-Amero, {Khaled K.} and Flavio Faletra and Paolo Gasparini and Fulvio Parentin and Stefano Pensiero and Alorainy, {Ibrahim A.} and Hellani, {Ali M.} and Dario Catalano and Thomas Bosley",
year = "2011",
month = "11",
doi = "10.3109/13816810.2011.574186",
language = "English (US)",
volume = "32",
pages = "212--216",
journal = "Ophthalmic Genetics",
issn = "1381-6810",
publisher = "Aeolus Press",
number = "4",

}

TY - JOUR

T1 - Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations

AU - Abu-Amero, Khaled K.

AU - Faletra, Flavio

AU - Gasparini, Paolo

AU - Parentin, Fulvio

AU - Pensiero, Stefano

AU - Alorainy, Ibrahim A.

AU - Hellani, Ali M.

AU - Catalano, Dario

AU - Bosley, Thomas

PY - 2011/11

Y1 - 2011/11

N2 - 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.

AB - 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.

KW - horizontal gaze palsy and progressive scoliosis

KW - ROBO3 gene

KW - scoliosis

UR - http://www.scopus.com/inward/record.url?scp=80054866145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054866145&partnerID=8YFLogxK

U2 - 10.3109/13816810.2011.574186

DO - 10.3109/13816810.2011.574186

M3 - Article

C2 - 21510772

AN - SCOPUS:80054866145

VL - 32

SP - 212

EP - 216

JO - Ophthalmic Genetics

JF - Ophthalmic Genetics

SN - 1381-6810

IS - 4

ER -