- Email: [email protected]
Progressive weakness in a 12-year-old boy
Journal of Clinical Neuroscience 18 (2011) 1751
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Images in Neuroscience: Answer
Progressive weakness in a 12-year-old boy Naveen Sankhyan a, Suvasini Sharma a, Anita Choudhary a, Sheffali Gulati a,⇑, Mehar Chand Sharma b, Pankaj Pathak b, Atin Kumar c a
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, Sri Aurobindo Marg Street, New Delhi 110029, India Department of Pathology, All India Institute of Medical Sciences, New Delhi, India c Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India b
1. Answer D. Calpainopathy. 2. Discussion A muscle biopsy was obtained, which showed features of muscular dystrophy and lobulated fibers on reduced nicotinamide adenine dinucleotide-tetrazolium (NADH-TR) staining. Immunohistochemistry for dystrophin, sarcoglycans (alpha, beta, gamma and delta), merosin, emerin and dysferlin revealed normal staining. Calpain-3 and dysferlin immunoblot analysis showed partial loss of calpain-3. The diagnosis of calpainopathy was concluded on the basis of clinical, muscle pathology and MRI findings. Calpainopathy is a type of autosomal recessive limb-girdle dystrophy caused by a deficiency of the enzyme calpain 3.1 Calpainopathy has a distinct clinical phenotype with predominant muscle atrophy, rather than hypertrophy.2 The average age of onset is 8 to 15 years. There is predominant involvement of gluteus maximus and hip adductors, with relative preservation of hip flexors and abductors. There is also marked involvement of the periscapular muscles causing scapular winging. The course is slowly progressive and life expectancy is not affected, as cardiac and respiratory muscles are usually spared.2 On muscle MRI, there is a striking and early involvement of the posterior thigh muscles.3 There is predominant involvement of the adductors and semi-membranous muscles in young patients, with minimal functional motor impairment and a more diffuse involvement of the posterolateral muscles of the thigh and the vastus
DOI of question: 10.1016/j.jocn.2010.07.134
⇑ Corresponding author. Tel.: +91 11 26594679; fax: +91 11 26588663. E-mail address: [email protected] (S. Gulati). 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.07.138
intermedius with relative sparing of the vastus lateralis, sartorius, and gracilis in patients with restricted ambulation. At the calf level, patients show involvement of the soleus muscle and the medial head of the gastrocnemius, with relative sparing of the lateral head. Similar MRI findings may be seen in limb-girdle muscular dystrophies-2I; however, there is more substantial involvement of muscles of the anterior compartment in limb girdle muscular dystrophies-2I, and a significant hypertrophy of the sartorius and gracilis muscles; and an absence of striking differential involvement between the medial and the lateral head of the gastrocnemius which is seen in calpainopathy.4 The definitive diagnosis relies on the identification of mutations in the calpain 3 gene (CAPN3); located on 15q15-q21.4 Diagnosis is complicated by absence of mutational hot spots in the calpain 3 gene.5
References 1. Sa’enz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype–phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732–42. 2. Bonnemann CG. Limb girdle muscular dystrophies. In: Jones Jr HR, De Vivo DC, Darras BT, editors. Neuromuscular disorders of infancy, childhood and adolescence: a clinician’s approach. Butterworth, Heinemann: Oxford; 2002. p. 717–52. 3. Mercuri E, Bushby K, Ricci E, et al. Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures. Neuro Disord 2005;15:164–71. 4. Mercuri E, Pichiecchio A, Allsop J, et al. Muscle MRI in inherited neuromuscular disorders: past, present, and future. J Magn Reson Imaging 2007;25:433–40. 5. Groen EJ, Charlton R, Baresi R, et al. Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A. Brain 2007;130:3237–49.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Images in Neuroscience: Answer
Progressive weakness in a 12-year-old boy Naveen Sankhyan a, Suvasini Sharma a, Anita Choudhary a, Sheffali Gulati a,⇑, Mehar Chand Sharma b, Pankaj Pathak b, Atin Kumar c a
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, Sri Aurobindo Marg Street, New Delhi 110029, India Department of Pathology, All India Institute of Medical Sciences, New Delhi, India c Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India b
1. Answer D. Calpainopathy. 2. Discussion A muscle biopsy was obtained, which showed features of muscular dystrophy and lobulated fibers on reduced nicotinamide adenine dinucleotide-tetrazolium (NADH-TR) staining. Immunohistochemistry for dystrophin, sarcoglycans (alpha, beta, gamma and delta), merosin, emerin and dysferlin revealed normal staining. Calpain-3 and dysferlin immunoblot analysis showed partial loss of calpain-3. The diagnosis of calpainopathy was concluded on the basis of clinical, muscle pathology and MRI findings. Calpainopathy is a type of autosomal recessive limb-girdle dystrophy caused by a deficiency of the enzyme calpain 3.1 Calpainopathy has a distinct clinical phenotype with predominant muscle atrophy, rather than hypertrophy.2 The average age of onset is 8 to 15 years. There is predominant involvement of gluteus maximus and hip adductors, with relative preservation of hip flexors and abductors. There is also marked involvement of the periscapular muscles causing scapular winging. The course is slowly progressive and life expectancy is not affected, as cardiac and respiratory muscles are usually spared.2 On muscle MRI, there is a striking and early involvement of the posterior thigh muscles.3 There is predominant involvement of the adductors and semi-membranous muscles in young patients, with minimal functional motor impairment and a more diffuse involvement of the posterolateral muscles of the thigh and the vastus
DOI of question: 10.1016/j.jocn.2010.07.134
⇑ Corresponding author. Tel.: +91 11 26594679; fax: +91 11 26588663. E-mail address: [email protected] (S. Gulati). 0967-5868/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2010.07.138
intermedius with relative sparing of the vastus lateralis, sartorius, and gracilis in patients with restricted ambulation. At the calf level, patients show involvement of the soleus muscle and the medial head of the gastrocnemius, with relative sparing of the lateral head. Similar MRI findings may be seen in limb-girdle muscular dystrophies-2I; however, there is more substantial involvement of muscles of the anterior compartment in limb girdle muscular dystrophies-2I, and a significant hypertrophy of the sartorius and gracilis muscles; and an absence of striking differential involvement between the medial and the lateral head of the gastrocnemius which is seen in calpainopathy.4 The definitive diagnosis relies on the identification of mutations in the calpain 3 gene (CAPN3); located on 15q15-q21.4 Diagnosis is complicated by absence of mutational hot spots in the calpain 3 gene.5
References 1. Sa’enz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype–phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005;128:732–42. 2. Bonnemann CG. Limb girdle muscular dystrophies. In: Jones Jr HR, De Vivo DC, Darras BT, editors. Neuromuscular disorders of infancy, childhood and adolescence: a clinician’s approach. Butterworth, Heinemann: Oxford; 2002. p. 717–52. 3. Mercuri E, Bushby K, Ricci E, et al. Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures. Neuro Disord 2005;15:164–71. 4. Mercuri E, Pichiecchio A, Allsop J, et al. Muscle MRI in inherited neuromuscular disorders: past, present, and future. J Magn Reson Imaging 2007;25:433–40. 5. Groen EJ, Charlton R, Baresi R, et al. Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A. Brain 2007;130:3237–49.