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Journal of Pediatric Genetics 3 (2014) 281–290 DOI 10.3233/PGE-14109 IOS Press
Genetics of strabismus and lid diseases Mohammad Ali A. Sadiqa,∗ and Munib ur Rehmanb a Institute b College
of Ophthalmology, Mayo Hospital Lahore, King Edward Medical University, Lahore, Pakistan of Ophthalmology and Allied Vision Sciences, King Edward Medical University, Lahore, Pakistan
Received 14 August 2014 Revised 12 September 2014 Accepted 15 September 2014
Abstract. The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births. The nuclear mutations identified in chronic progressive external ophthalmoplegia harbor multiple mtDNA deletions that include POLG mutations, PEO1 mutations, OPA1 mutations and RRM2B mutations. In Kearns-Sayre syndrome, the spontaneous mitochondrial deletions vary from 1.3 to 8.0 kb subunits of the oxidative phosphorylation enzymes and several t-RNA genes are affected. Oculopharyngeal muscle dystrophy is both autosomal dominant and recessive form. Congenital fibrosis of extraocular muscles (CFEOM) 1 has mutations in KIF21A on chromosome 12 with TUBB3 mutation also being seen. CFEOM 2 is an autosomal recessive, genetically distinct entity with homozygous mutations in PHOX2A. CFEOM 3 is autosomal dominant heterozygous missense mutations in TUBB3. Most cases of Mobius syndrome are sporadic with familial cases being autosomal dominant, autosomal recessive or X-linked recessive inheritance. Genetic testing has shown abnormalities involving chromosome 1 and 13. Presynaptic congenital myasthenic syndrome is caused by ChAT (choline acetyltransferase) mutation. Two loci have been found for myotonic dystrophy (DM). DM1, which is associated with trinucleotide expansion on chromosome 19q13.3 and DM2 which is associated with CCTG tetranucleotide expansion at 3q21. Blepharophimosis is caused by mutations in the FOXL2 gene 49 located at chromosome 3q23. Lymphedema-distichiasis is an autosomal dominant disorder caused by mutations in the FOXC2 gene. Keywords: Genetics, eyelid, strabismus, chronic progressive external ophthalmoplegia, blepharophimosis, myasthenic syndromes, Mobius syndrome
1. Introduction Recent advances in genetic studies have opened a new era for medicine. Molecular biology has paved the way in identifying disease as well as understanding their etiologies. Furthermore, it is playing a major role in determining the risk of transmission of a particular disease to the next generation. This has enabled the ∗ Corresponding author: Mohammad Ali A. Sadiq, MD, Eye Unit III, Institute of Ophthalmology, Mayo Hospital Lahore, King Edward Medical University, Mayo Hospital Road, Nelagumbad, Anarkali, Lahore 54000, Pakistan. Tel.: +92 42 99211145; E-mail: [email protected].
caregivers to take pre-emptive measures in treating the disease and managing its complications. Ocular and peri-ocular malformations may occur in isolation, in combination with, or as part of some systemic malformation syndrome. The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births [1]. There is very less information available regarding the etiology of ocular ailments related to eyelids and the extra-ocular muscles. However, a lot of insight has been gained into the genetic basis of incomitant strabismus that has helped in understanding the complexity of the molecular basis of these misalignments, and also
2146-4596/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
Journal of Pediatric Genetics 3 (2014) 281–290 DOI 10.3233/PGE-14109 IOS Press
Genetics of strabismus and lid diseases Mohammad Ali A. Sadiqa,∗ and Munib ur Rehmanb a Institute b College
of Ophthalmology, Mayo Hospital Lahore, King Edward Medical University, Lahore, Pakistan of Ophthalmology and Allied Vision Sciences, King Edward Medical University, Lahore, Pakistan
Received 14 August 2014 Revised 12 September 2014 Accepted 15 September 2014
Abstract. The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births. The nuclear mutations identified in chronic progressive external ophthalmoplegia harbor multiple mtDNA deletions that include POLG mutations, PEO1 mutations, OPA1 mutations and RRM2B mutations. In Kearns-Sayre syndrome, the spontaneous mitochondrial deletions vary from 1.3 to 8.0 kb subunits of the oxidative phosphorylation enzymes and several t-RNA genes are affected. Oculopharyngeal muscle dystrophy is both autosomal dominant and recessive form. Congenital fibrosis of extraocular muscles (CFEOM) 1 has mutations in KIF21A on chromosome 12 with TUBB3 mutation also being seen. CFEOM 2 is an autosomal recessive, genetically distinct entity with homozygous mutations in PHOX2A. CFEOM 3 is autosomal dominant heterozygous missense mutations in TUBB3. Most cases of Mobius syndrome are sporadic with familial cases being autosomal dominant, autosomal recessive or X-linked recessive inheritance. Genetic testing has shown abnormalities involving chromosome 1 and 13. Presynaptic congenital myasthenic syndrome is caused by ChAT (choline acetyltransferase) mutation. Two loci have been found for myotonic dystrophy (DM). DM1, which is associated with trinucleotide expansion on chromosome 19q13.3 and DM2 which is associated with CCTG tetranucleotide expansion at 3q21. Blepharophimosis is caused by mutations in the FOXL2 gene 49 located at chromosome 3q23. Lymphedema-distichiasis is an autosomal dominant disorder caused by mutations in the FOXC2 gene. Keywords: Genetics, eyelid, strabismus, chronic progressive external ophthalmoplegia, blepharophimosis, myasthenic syndromes, Mobius syndrome
1. Introduction Recent advances in genetic studies have opened a new era for medicine. Molecular biology has paved the way in identifying disease as well as understanding their etiologies. Furthermore, it is playing a major role in determining the risk of transmission of a particular disease to the next generation. This has enabled the ∗ Corresponding author: Mohammad Ali A. Sadiq, MD, Eye Unit III, Institute of Ophthalmology, Mayo Hospital Lahore, King Edward Medical University, Mayo Hospital Road, Nelagumbad, Anarkali, Lahore 54000, Pakistan. Tel.: +92 42 99211145; E-mail: [email protected].
caregivers to take pre-emptive measures in treating the disease and managing its complications. Ocular and peri-ocular malformations may occur in isolation, in combination with, or as part of some systemic malformation syndrome. The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births [1]. There is very less information available regarding the etiology of ocular ailments related to eyelids and the extra-ocular muscles. However, a lot of insight has been gained into the genetic basis of incomitant strabismus that has helped in understanding the complexity of the molecular basis of these misalignments, and also
2146-4596/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
