Pediatric Neurology 50 (2014) 279e280
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Ataxia Telangiectasia in a Three-Year-Old-Girl Kathryn Anne Hosking M. Orth a, *, Harry Leung MBBS (Hons), FRANZCO a, Ian Andrews MBBS, FRACP b, Rani Sachdev MBBS, FRACP c a
Southern Ophthalmology, Kogarah, Sydney, Australia Neurology, Sydney Children’s Hospital, Randwick, NSW, Australia c Department of Medical Genetics, Sydney Children’s Hospital, Randwick, NSW, Australia b
Ataxia telangiectasia (AT) is a rare autosomal-recessive condition characterized by ataxia and telangiectasia of the eyes, face, and neck.1 The incidence of AT is approximately 1 in 100,000 live births.1 Ataxia is usually the initial symptom, often noted within the first 2 years of life, when the child begins to sit and walk.1,2 Telangiectasias tend to develop between the ages of 2 and 8 years.2 We present AT in a 3year-old girl, whereby diagnosis was elucidated by the presence of ocular telangiectasia. The patient was referred to the ophthalmologist by her physician, who reported poor motor skills and frequent falls. Her parents first noted a head tilt and a lean in her sitting posture at 6 months of age. She began walking at 18 months of age but was always unsteady. Speech development was age appropriate, but she had recently begun drooling and slurring words. Vision with pictures was 6/9 in the right eye and 6/6 in the left. Ocular motility was normal, and oculomotor apraxia was absent. Telangiectasia of the bulbar conjunctiva was noted bilaterally (Fig). Findings of the ocular examination, including fundi, were normal, with absence of telangiectasia in the retinal vasculature. The patient was subsequently referred for neurological and genetic assessment with a provisional diagnosis of AT. Laboratory testing revealed elevated alpha-fetoprotein, low levels of immunoglobulin A, and lymphopenia, findings consistent with AT. Comparative genomic hybridization array excluded a cryptic chromosomal abnormality. Analysis of the ATM gene revealed a homozygous mutation in exon 13 (c1931 C > G p.S664X). AT is a progressive disorder characterized by cerebellar ataxia, telangiectasia, immune defects, and predisposition to malignancy, such as leukemias, lymphomas, and tumors of the brain, stomach, breasts and gonads.3 Other
* Communications should be addressed to: Kathryn Hosking; c/Southern Ophthalmology Suite 2A; Level 2, 4 Belgrave Street; Kogarah, NSW, Australia 2217. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.011
FIGURE. Telangiectasia of the conjunctiva. (The color version of this figure is available in the online edition.)
neurological symptoms include difficulty with speech and swallowing, oculomotor apraxia, and involuntary movements.1,2 By age 10-15 years, most affected children are wheel-chair bound as the result of ataxia. The ATM gene is situated at chromosome 11q23 and codes for the ATM protein (ataxia-telangiectasia mutated kinase). It is a member of the phosphatidyl-inositol 3-kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell-cycle control.4 Homozygous mutations of this gene result in the AT phenotype. Recognition of ocular telangiectasia or oculomotor apraxia allows immediate consideration of AT and directs specific testing. Telangiectasia typically develops between 3 and 5 years of age, and ataxia may be misdiagnosed as ataxic cerebral palsy before the appearance of oculocutaneous telangiectasia. Specific diagnosis facilitates the management of progressive neurological difficulties and genetic counseling.
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K.A. Hosking et al. / Pediatric Neurology 50 (2014) 279e280
References 1. Moin M, Aghamohammadi A, Kouhi A, et al. Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatr Neurol. 2007;37:21-28. 2. Lavin MF, Gueven N, Bottle S, Gatti RA. Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. Br Med Bull. 2007;81&82:129-147.
3. Mavrou A, Tsangaris GTh, Roma E, Kolialexi A. The ATM gene and ataxia telangiectasia. Anticancer Res. 2008;28:401-406. 4. Klockgether T, Paulson H. Milestones in ataxia. Mov Disord. 2011;26: 1134-1141.
The most interesting information comes from children, for they tell all they know and then stop. Mark Twain
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Ataxia Telangiectasia in a Three-Year-Old-Girl Kathryn Anne Hosking M. Orth a, *, Harry Leung MBBS (Hons), FRANZCO a, Ian Andrews MBBS, FRACP b, Rani Sachdev MBBS, FRACP c a
Southern Ophthalmology, Kogarah, Sydney, Australia Neurology, Sydney Children’s Hospital, Randwick, NSW, Australia c Department of Medical Genetics, Sydney Children’s Hospital, Randwick, NSW, Australia b
Ataxia telangiectasia (AT) is a rare autosomal-recessive condition characterized by ataxia and telangiectasia of the eyes, face, and neck.1 The incidence of AT is approximately 1 in 100,000 live births.1 Ataxia is usually the initial symptom, often noted within the first 2 years of life, when the child begins to sit and walk.1,2 Telangiectasias tend to develop between the ages of 2 and 8 years.2 We present AT in a 3year-old girl, whereby diagnosis was elucidated by the presence of ocular telangiectasia. The patient was referred to the ophthalmologist by her physician, who reported poor motor skills and frequent falls. Her parents first noted a head tilt and a lean in her sitting posture at 6 months of age. She began walking at 18 months of age but was always unsteady. Speech development was age appropriate, but she had recently begun drooling and slurring words. Vision with pictures was 6/9 in the right eye and 6/6 in the left. Ocular motility was normal, and oculomotor apraxia was absent. Telangiectasia of the bulbar conjunctiva was noted bilaterally (Fig). Findings of the ocular examination, including fundi, were normal, with absence of telangiectasia in the retinal vasculature. The patient was subsequently referred for neurological and genetic assessment with a provisional diagnosis of AT. Laboratory testing revealed elevated alpha-fetoprotein, low levels of immunoglobulin A, and lymphopenia, findings consistent with AT. Comparative genomic hybridization array excluded a cryptic chromosomal abnormality. Analysis of the ATM gene revealed a homozygous mutation in exon 13 (c1931 C > G p.S664X). AT is a progressive disorder characterized by cerebellar ataxia, telangiectasia, immune defects, and predisposition to malignancy, such as leukemias, lymphomas, and tumors of the brain, stomach, breasts and gonads.3 Other
* Communications should be addressed to: Kathryn Hosking; c/Southern Ophthalmology Suite 2A; Level 2, 4 Belgrave Street; Kogarah, NSW, Australia 2217. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2013.11.011
FIGURE. Telangiectasia of the conjunctiva. (The color version of this figure is available in the online edition.)
neurological symptoms include difficulty with speech and swallowing, oculomotor apraxia, and involuntary movements.1,2 By age 10-15 years, most affected children are wheel-chair bound as the result of ataxia. The ATM gene is situated at chromosome 11q23 and codes for the ATM protein (ataxia-telangiectasia mutated kinase). It is a member of the phosphatidyl-inositol 3-kinase family of proteins that respond to DNA damage by phosphorylating key substrates involved in DNA repair and/or cell-cycle control.4 Homozygous mutations of this gene result in the AT phenotype. Recognition of ocular telangiectasia or oculomotor apraxia allows immediate consideration of AT and directs specific testing. Telangiectasia typically develops between 3 and 5 years of age, and ataxia may be misdiagnosed as ataxic cerebral palsy before the appearance of oculocutaneous telangiectasia. Specific diagnosis facilitates the management of progressive neurological difficulties and genetic counseling.
280
K.A. Hosking et al. / Pediatric Neurology 50 (2014) 279e280
References 1. Moin M, Aghamohammadi A, Kouhi A, et al. Ataxia-telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatr Neurol. 2007;37:21-28. 2. Lavin MF, Gueven N, Bottle S, Gatti RA. Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. Br Med Bull. 2007;81&82:129-147.
3. Mavrou A, Tsangaris GTh, Roma E, Kolialexi A. The ATM gene and ataxia telangiectasia. Anticancer Res. 2008;28:401-406. 4. Klockgether T, Paulson H. Milestones in ataxia. Mov Disord. 2011;26: 1134-1141.
The most interesting information comes from children, for they tell all they know and then stop. Mark Twain
