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Familial monomelic amyotrophy: a case report from India
Journal of the Neurological Sciences 220 (2004) 95 – 98 www.elsevier.com/locate/jns
Familial monomelic amyotrophy: a case report from India A. Nalini *, L. Lokesh, E. Ratnavalli Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India Received 19 September 2003; received in revised form 23 January 2004; accepted 23 February 2004
Abstract Monomelic amyotrophy (MMA) is a benign lower motor neuron disorder in the young with male preponderance. It is characterized by insidious onset and progressive weakness and wasting of a distal extremity over a few years followed by spontaneous arrest. The exact pathogenesis is unknown. It is predominantly a sporadic disorder but rarely familial forms have been documented. In this report, we describe the phenotype of a 21-year-old man and his mother who were diagnosed to have MMA. The index case presented with left upper limb weakness and wasting of 3 years duration while his mother had right upper limb amyotrophy and weakness of 34 years. A total of 190 patients were diagnosed to have MMA in our institute over the last 27 years and this is the first case of familial MMA. D 2004 Elsevier B.V. All rights reserved. Keywords: Familial monomelic amyotrophy; India
1. Introduction Monomelic Amyotrophy (MMA) is a rare disorder predominantly affecting young men in the second and third decades with a unique geographic distribution. Most cases have been reported from Asia including India, Japan [1– 4] and other East Asian countries. A few cases have also been reported from the West [5– 7]. The disease is characterized by insidious onset weakness and wasting restricted to a single upper or lower limb which usually progresses for a few years followed by spontaneous arrest. There is no involvement of sensory, pyramidal or extrapyramidal systems. Uncommon features are coldness of the affected hand, cold paresis, hyperhidrosis [1,3] and associated abnormalities of sympathetic skin response [8]. The precise cause for this disorder is yet unknown; however, various postulations including flexion induced myelopathy [9] and atopy [10] are considered to be contributing factors. Familial occurrence of MMA is rare, but a few reports of siblings affected with MMA suggest the possibility of autosomal recessive inheritance [11 – 14], while others mention a father and son affected with MMA implying an autosomal dominant inheritance pattern [15,16].
* Corresponding author. Tel.: +91-80-6995150; fax: +91-80-6564830. E-mail address: [email protected] (A. Nalini). 0022-510X/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2004.02.015
In this report, we describe the clinical and electromyographic features of a 54-year-old lady with Brachial Monomelic Amyotrophy (BMMA) of the right upper limb and her son with BMMA of the left upper limb. 1.1. Index case A 21-year-old man hailing from Manipur, state of Assam in North East India was admitted to our hospital in April 2003 with insidious onset, gradually progressive weakness and wasting of small muscles of left hand and forearm of 3 years. The initial symptom was difficulty in grasping the nail cutter firmly suggesting weakness of the abductor pollicis brevis (APB), opponens pollicis (OP), lumbricals and the long flexors of the hand on the left side. The weakness and wasting progressed over 1 year and stabilized. He had difficulty in performing fine work like buttoning, unbuttoning and gripping objects firmly. One year after the onset of illness, he developed fasciculations over the left arm and forearm followed by tremulousness of the hand with clawing. There was positive history of cold paresis with exacerbation of motor weakness on exposure to cold. The illness had attained a stationary phase at the end of 1 year 3 months. There was no history of poliomyelitis, cervical trauma, fracture or surgery of the left upper limb. There was no exposure to toxins or heavy metals or symptoms to suggest allergic phenomenon or atopy in the
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negative for rheumatoid arthritis factor and antinuclear antibodies. Total serum h-n-acetylhexosaminidase level including hexosaminidase A and B were normal. Electromyography (EMG) revealed evidence of spontaneous activity with occasional fibrillation potentials in the first dorsal interossei and fasciculations with high amplitude long duration motor unit potentials (MUPs) in the biceps, triceps and extensor digitorum communis suggestive of chronic denervation with reinnervation. Interference pattern was incomplete in all the sampled muscles. EMG of the right upper limb and both lower limbs was normal. Motor conductions revealed minimally reduced amplitudes of the compound muscle action potential (CMAP) recorded from APB and ADM. Sensory and motor conduction velocities and ‘F’ wave latencies were normal in all extremities including the affected limb and there was no conduction block. Cerebrospinal fluid analysis was normal. Magnetic Resonance Imaging (MRI) with gadolinium enhancement of the spinal cord (Fig. 2) and brain was normal. 1.2. Case report of mother
Fig. 1. Volar view showing atrophy of left forearm and small muscles of the hand.
patient or in the family. There were no symptoms related to cranial nerve involvement or sensory disturbances. The neurological disability was mild and he was able to perform all activities of daily living. There was history of similar illness in the patient’s mother (described below). On examination, there was mild wasting of the deltoid, biceps, triceps and moderate wasting of the forearm and all small muscles of the hand with predominant involvement of the lateral aspect of the left hand (Fig. 1). There was clawing with minipolymyoclonus and fasciculations were observed over the arm and forearm muscles and mild hypotonia was noted at the wrist joint. Muscle power according to Medical Research Council assessment was grade 5 in the shoulder girdle and arm muscles, grade 4 in the extensor digitorum and grade 3 in the small muscles of the hand including APB, OP, dorsal and palmar interossei, abductor digiti minimi (ADM), flexor digiti minimi (FDM), opponens digiti minimi and lumbricals. Muscle power in the right upper limb and both lower limbs was normal and there was no wasting. The deep tendon reflexes were brisk in the affected upper limb and exaggerated in the other limbs. Plantar response was flexor bilaterally. There was no cranial nerve palsy or sensory disturbances. Investigations revealed normal blood counts with no eosinophilia. Serum electrolytes, creatine kinase, urea, creatinine, liver and thyroid functions were normal. Serum was
A 54-year-old housewife, mother of proband was also examined during the same period. At the age of 20 years, she first noticed symptoms of cold paresis in the right hand with stiffness of the fingers and extreme difficulty to perform her daily activities on exposure to cold conditions and during the winter season. About 10 years later, she
Fig. 2. T2-weighted sagittal MR image of cervical spinal cord showing normal findings.
A. Nalini et al. / Journal of the Neurological Sciences 220 (2004) 95–98
97
stationary phase. There was no other significant history. The most disturbing symptom was the intense cold paresis and significant disability during the winter months. On examination, there was moderate wasting of the forearm muscles and severe wasting of the small muscles of the hand including the extensor digitorum, extensor carpi ulnaris, thenar (APB, OP), hypothenar muscles (ADM, FDM), the interossei and the lumbricals (Fig. 3a and b) and clawing of the right hand. Brachioradialis muscle was spared. The arm and shoulder girdle muscles were normal. Muscle power was normal in the proximal groups, grade 4 in extensor digitorum and flexor carpi ulnaris and thenar, hypothenar and other small muscles of the hand were moderately weak. There was bilateral minipolymyoclonus of outstretched hands and this was more pronounced on the right side. The deep tendon reflexes were symmetrically brisk in all the limbs and plantar response was flexor on both sides. The cranial nerves, sensory and cerebellar systems were normal. Investigations including hemogram, routine serum chemistry were normal and work up for vasculitis was negative. Cerebrospinal fluid analysis was normal. Needle electromyography of the right biceps, triceps, APB, ADM and extensor digitorum communis revealed evidence of fasciculation potentials, giant motor unit potentials and long duration MUPs suggesting chronic denervation with reinnervation. EMG of proximal and distal muscles in the other
Fig. 3. (a) Volar aspect showing predominant atrophy of hypothenar and interossei muscles on right side. (b) Dorsal aspect showing atrophy of interossei and forearm muscles with sparing of brachioradialis on right side.
developed insidious onset gradually progressive weakness and wasting of the small muscles of the right hand and forearm muscles associated with clawing and tremulousness of the fingers. She noticed occasional fasciculations over the forearm muscles. She had mild difficulty in performing fine work such as cutting vegetables and stitching but was able to perform all other activities of daily living. The neurological deficit progressed for 3 years and then attained a
Fig. 4. T2 sagittal MR image of cervical spinal cord showing focal hyperintensity of cord at C4 level.
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three limbs was normal. Nerve conductions including motor and sensory were normal except for minimally reduced CMAP amplitudes recorded from APB and ADM. There was no evidence of conduction block. Cervical MRI showed evidence of focal hyperintensity opposite C4 level (Fig. 4) and hyperintense signals in the region of the grey matter at C4,5 levels bilaterally in axial T2 weighted sequences.
2. Discussion Since the first report of Monomelic amyotrophy in 1959 by Hirayama et al. [1], there has been a total of seven reports of familial MMA in the English literature. In five families, siblings were affected suggesting the possibility of autosomal recessive inheritance [11 – 14,17]. Hirayama et al. described two brothers with onset at 13 and 15 years [11]. Identical male twins with disease onset at 16 and 17 years was reported by Tandan et al. [12]. Interestingly, all the affected siblings were males. In the remaining two reports of familial MMA, the father and son were affected implying an autosomal dominant inheritance [15,16]. Schlegel et al. reported the occurrence of MMA in a father aged 53 years with onset at 16 years and similar disorder in his only son aged 18 years with onset also at 16 years of age. In our series of 190 cases (unpublished) seen over the last 27 years, this is the first case of familial MMA. Both the patients described here exhibited the classical features of BMMA [3,18]. Although the deep tendon reflexes were exaggerated in the affected and unaffected limbs in both the patients, there was no Babinski sign. Hyperactive deep tendon reflexes (DTRs) restricted to the affected limb or present in the affected and unaffected limbs have been described in a few reports [14,15,18]. Cervical MRI showed hyperintense signals involving the grey matter in the mother but was normal in the son. A study on imaging in MMA revealed focal atrophy and foci of signal alterations in cervical cord in seven patients supporting the theory of intrinsic cord pathology [19]. Forward displacement of the lower dural sac and injury to the cord during flexion has been proposed as a mechanism for MMA but it would be extremely difficult to postulate this mechanical reason as a common cause for the illness in both our patients [9]. However, we did not perform MRI of the cervical spine in flexion to study the forward displacement of the lower dural sac. Based on the neuropathological findings [11], ischaemic degeneration of the anterior horn cells has been proposed as another mechanism for MMA, but this is not well understood and hence it may not be possible to entertain ischaemia as the common causative factor in our patients. In one report of familial MMA the five exons of the Superoxide Dismutase 1 gene were normal [14]. We were unable to perform any genetic studies for evidence of mutations in the gene encoding the copper – zinc superoxide dismutase.
Familial forms of BMMA are rare and till date, only eight families including this report have been described in the English literature.
References [1] Hirayama K, Toyokura Y, Tsubaki T. Juvenile muscular atrophy of unilateral upper extremity; a new clinical entity. Psychiatr Neurol Jpn 1959;61:2190 – 7. [2] Hirayama K, Tsubaki T, Toyokura Y, Okinaka S. Juvenile muscular atrophy of unilateral upper extremities. Neurology 1963;13:373 – 80. [3] Gourie-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol 1984;41:388 – 94. [4] Peires JB, Seneviratne KN, Wicremasinghe HR, Gunatilake SB, Gamage R. Non-familial juvenile distal spinal muscular atrophy of upper extremity. J Neurol Neurosurg Psychiatry 1989;52:314 – 9. [5] Compernolle T. A case of juvenile muscular atrophy confined to one upper limb. Eur Neurol 1973;102:37 – 42. [6] Serratrice G, Pellissier JP, Pouget J. Etude nosologique de 25 cas d’amyotrophie monomelique chronique. Rev Neurol (Paris) 1987; 143:201 – 10. [7] De Visser M, De Visser BWO, Verbeeten B. Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy. Eur Neurol 1988;28:135 – 8. [8] Gourie-Devi M, Nalini A. Sympathetic skin response in monomelic amyotrophy. Acta Neurol Scand 2001;1:162 – 6. [9] Hirayama K, Tokumara Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 2000;54:1922 – 6. [10] Kira J, Ochi H. Juvenile muscular atrophy of the distal upper limb (Hirayama disease) associated with atopy. J Neurol Neurosurg Psychiatry 2001;6:798 – 801. [11] Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry 1987;50:285 – 90. [12] Tandan R, Sharma KR, Bradley WG, Bevan H, Jacobsen P. Chronic segmental spinal muscular atrophy of upper extremities in identical twins. Neurology 1990;40:236 – 9. [13] Mishra UK, Kalita J. Central motor conduction in Hirayama disease. Electroencephalogr Clin Neurophysiol 1995;97:73 – 6. [14] Robberecht W, Aguirre T, Van den Bosch L, Theys P, Nees H, Cassiman JJ, et al. Familial juvenile focal amyotrophy of the upper extremity (Hirayama disease). Superoxide dismutase genotype and activity. Arch Neurol 1997;54:46 – 50. [15] Sobue I, Saito N, Lida M, Ando K. Juvenile type of distal and segmental muscular atrophy of upper extremities. Ann Neurol 1978; 3:429 – 32. [16] Schlegel U, Jerusalem F, Tachmann W, Cordt A, Tsuda Y. Benign juvenile focal muscular atrophy of upper extremities: a familial case. J Neurol Sci 1987;80:351 – 3. [17] Gucuyener K, Aysun S, Topalogu H, Inan L, Varli K. Monomelic amyotrophy in siblings. Pediatr Neurol 1991;7:220 – 2. [18] Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand 2003;107: 215 – 20. [19] Schroder R, Keller E, Flacke S, Schmidt S, Pohl C, Klockgether T, et al. MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease? J Neurol 1999;246: 1069 – 74.
Familial monomelic amyotrophy: a case report from India A. Nalini *, L. Lokesh, E. Ratnavalli Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India Received 19 September 2003; received in revised form 23 January 2004; accepted 23 February 2004
Abstract Monomelic amyotrophy (MMA) is a benign lower motor neuron disorder in the young with male preponderance. It is characterized by insidious onset and progressive weakness and wasting of a distal extremity over a few years followed by spontaneous arrest. The exact pathogenesis is unknown. It is predominantly a sporadic disorder but rarely familial forms have been documented. In this report, we describe the phenotype of a 21-year-old man and his mother who were diagnosed to have MMA. The index case presented with left upper limb weakness and wasting of 3 years duration while his mother had right upper limb amyotrophy and weakness of 34 years. A total of 190 patients were diagnosed to have MMA in our institute over the last 27 years and this is the first case of familial MMA. D 2004 Elsevier B.V. All rights reserved. Keywords: Familial monomelic amyotrophy; India
1. Introduction Monomelic Amyotrophy (MMA) is a rare disorder predominantly affecting young men in the second and third decades with a unique geographic distribution. Most cases have been reported from Asia including India, Japan [1– 4] and other East Asian countries. A few cases have also been reported from the West [5– 7]. The disease is characterized by insidious onset weakness and wasting restricted to a single upper or lower limb which usually progresses for a few years followed by spontaneous arrest. There is no involvement of sensory, pyramidal or extrapyramidal systems. Uncommon features are coldness of the affected hand, cold paresis, hyperhidrosis [1,3] and associated abnormalities of sympathetic skin response [8]. The precise cause for this disorder is yet unknown; however, various postulations including flexion induced myelopathy [9] and atopy [10] are considered to be contributing factors. Familial occurrence of MMA is rare, but a few reports of siblings affected with MMA suggest the possibility of autosomal recessive inheritance [11 – 14], while others mention a father and son affected with MMA implying an autosomal dominant inheritance pattern [15,16].
* Corresponding author. Tel.: +91-80-6995150; fax: +91-80-6564830. E-mail address: [email protected] (A. Nalini). 0022-510X/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2004.02.015
In this report, we describe the clinical and electromyographic features of a 54-year-old lady with Brachial Monomelic Amyotrophy (BMMA) of the right upper limb and her son with BMMA of the left upper limb. 1.1. Index case A 21-year-old man hailing from Manipur, state of Assam in North East India was admitted to our hospital in April 2003 with insidious onset, gradually progressive weakness and wasting of small muscles of left hand and forearm of 3 years. The initial symptom was difficulty in grasping the nail cutter firmly suggesting weakness of the abductor pollicis brevis (APB), opponens pollicis (OP), lumbricals and the long flexors of the hand on the left side. The weakness and wasting progressed over 1 year and stabilized. He had difficulty in performing fine work like buttoning, unbuttoning and gripping objects firmly. One year after the onset of illness, he developed fasciculations over the left arm and forearm followed by tremulousness of the hand with clawing. There was positive history of cold paresis with exacerbation of motor weakness on exposure to cold. The illness had attained a stationary phase at the end of 1 year 3 months. There was no history of poliomyelitis, cervical trauma, fracture or surgery of the left upper limb. There was no exposure to toxins or heavy metals or symptoms to suggest allergic phenomenon or atopy in the
96
A. Nalini et al. / Journal of the Neurological Sciences 220 (2004) 95–98
negative for rheumatoid arthritis factor and antinuclear antibodies. Total serum h-n-acetylhexosaminidase level including hexosaminidase A and B were normal. Electromyography (EMG) revealed evidence of spontaneous activity with occasional fibrillation potentials in the first dorsal interossei and fasciculations with high amplitude long duration motor unit potentials (MUPs) in the biceps, triceps and extensor digitorum communis suggestive of chronic denervation with reinnervation. Interference pattern was incomplete in all the sampled muscles. EMG of the right upper limb and both lower limbs was normal. Motor conductions revealed minimally reduced amplitudes of the compound muscle action potential (CMAP) recorded from APB and ADM. Sensory and motor conduction velocities and ‘F’ wave latencies were normal in all extremities including the affected limb and there was no conduction block. Cerebrospinal fluid analysis was normal. Magnetic Resonance Imaging (MRI) with gadolinium enhancement of the spinal cord (Fig. 2) and brain was normal. 1.2. Case report of mother
Fig. 1. Volar view showing atrophy of left forearm and small muscles of the hand.
patient or in the family. There were no symptoms related to cranial nerve involvement or sensory disturbances. The neurological disability was mild and he was able to perform all activities of daily living. There was history of similar illness in the patient’s mother (described below). On examination, there was mild wasting of the deltoid, biceps, triceps and moderate wasting of the forearm and all small muscles of the hand with predominant involvement of the lateral aspect of the left hand (Fig. 1). There was clawing with minipolymyoclonus and fasciculations were observed over the arm and forearm muscles and mild hypotonia was noted at the wrist joint. Muscle power according to Medical Research Council assessment was grade 5 in the shoulder girdle and arm muscles, grade 4 in the extensor digitorum and grade 3 in the small muscles of the hand including APB, OP, dorsal and palmar interossei, abductor digiti minimi (ADM), flexor digiti minimi (FDM), opponens digiti minimi and lumbricals. Muscle power in the right upper limb and both lower limbs was normal and there was no wasting. The deep tendon reflexes were brisk in the affected upper limb and exaggerated in the other limbs. Plantar response was flexor bilaterally. There was no cranial nerve palsy or sensory disturbances. Investigations revealed normal blood counts with no eosinophilia. Serum electrolytes, creatine kinase, urea, creatinine, liver and thyroid functions were normal. Serum was
A 54-year-old housewife, mother of proband was also examined during the same period. At the age of 20 years, she first noticed symptoms of cold paresis in the right hand with stiffness of the fingers and extreme difficulty to perform her daily activities on exposure to cold conditions and during the winter season. About 10 years later, she
Fig. 2. T2-weighted sagittal MR image of cervical spinal cord showing normal findings.
A. Nalini et al. / Journal of the Neurological Sciences 220 (2004) 95–98
97
stationary phase. There was no other significant history. The most disturbing symptom was the intense cold paresis and significant disability during the winter months. On examination, there was moderate wasting of the forearm muscles and severe wasting of the small muscles of the hand including the extensor digitorum, extensor carpi ulnaris, thenar (APB, OP), hypothenar muscles (ADM, FDM), the interossei and the lumbricals (Fig. 3a and b) and clawing of the right hand. Brachioradialis muscle was spared. The arm and shoulder girdle muscles were normal. Muscle power was normal in the proximal groups, grade 4 in extensor digitorum and flexor carpi ulnaris and thenar, hypothenar and other small muscles of the hand were moderately weak. There was bilateral minipolymyoclonus of outstretched hands and this was more pronounced on the right side. The deep tendon reflexes were symmetrically brisk in all the limbs and plantar response was flexor on both sides. The cranial nerves, sensory and cerebellar systems were normal. Investigations including hemogram, routine serum chemistry were normal and work up for vasculitis was negative. Cerebrospinal fluid analysis was normal. Needle electromyography of the right biceps, triceps, APB, ADM and extensor digitorum communis revealed evidence of fasciculation potentials, giant motor unit potentials and long duration MUPs suggesting chronic denervation with reinnervation. EMG of proximal and distal muscles in the other
Fig. 3. (a) Volar aspect showing predominant atrophy of hypothenar and interossei muscles on right side. (b) Dorsal aspect showing atrophy of interossei and forearm muscles with sparing of brachioradialis on right side.
developed insidious onset gradually progressive weakness and wasting of the small muscles of the right hand and forearm muscles associated with clawing and tremulousness of the fingers. She noticed occasional fasciculations over the forearm muscles. She had mild difficulty in performing fine work such as cutting vegetables and stitching but was able to perform all other activities of daily living. The neurological deficit progressed for 3 years and then attained a
Fig. 4. T2 sagittal MR image of cervical spinal cord showing focal hyperintensity of cord at C4 level.
98
A. Nalini et al. / Journal of the Neurological Sciences 220 (2004) 95–98
three limbs was normal. Nerve conductions including motor and sensory were normal except for minimally reduced CMAP amplitudes recorded from APB and ADM. There was no evidence of conduction block. Cervical MRI showed evidence of focal hyperintensity opposite C4 level (Fig. 4) and hyperintense signals in the region of the grey matter at C4,5 levels bilaterally in axial T2 weighted sequences.
2. Discussion Since the first report of Monomelic amyotrophy in 1959 by Hirayama et al. [1], there has been a total of seven reports of familial MMA in the English literature. In five families, siblings were affected suggesting the possibility of autosomal recessive inheritance [11 – 14,17]. Hirayama et al. described two brothers with onset at 13 and 15 years [11]. Identical male twins with disease onset at 16 and 17 years was reported by Tandan et al. [12]. Interestingly, all the affected siblings were males. In the remaining two reports of familial MMA, the father and son were affected implying an autosomal dominant inheritance [15,16]. Schlegel et al. reported the occurrence of MMA in a father aged 53 years with onset at 16 years and similar disorder in his only son aged 18 years with onset also at 16 years of age. In our series of 190 cases (unpublished) seen over the last 27 years, this is the first case of familial MMA. Both the patients described here exhibited the classical features of BMMA [3,18]. Although the deep tendon reflexes were exaggerated in the affected and unaffected limbs in both the patients, there was no Babinski sign. Hyperactive deep tendon reflexes (DTRs) restricted to the affected limb or present in the affected and unaffected limbs have been described in a few reports [14,15,18]. Cervical MRI showed hyperintense signals involving the grey matter in the mother but was normal in the son. A study on imaging in MMA revealed focal atrophy and foci of signal alterations in cervical cord in seven patients supporting the theory of intrinsic cord pathology [19]. Forward displacement of the lower dural sac and injury to the cord during flexion has been proposed as a mechanism for MMA but it would be extremely difficult to postulate this mechanical reason as a common cause for the illness in both our patients [9]. However, we did not perform MRI of the cervical spine in flexion to study the forward displacement of the lower dural sac. Based on the neuropathological findings [11], ischaemic degeneration of the anterior horn cells has been proposed as another mechanism for MMA, but this is not well understood and hence it may not be possible to entertain ischaemia as the common causative factor in our patients. In one report of familial MMA the five exons of the Superoxide Dismutase 1 gene were normal [14]. We were unable to perform any genetic studies for evidence of mutations in the gene encoding the copper – zinc superoxide dismutase.
Familial forms of BMMA are rare and till date, only eight families including this report have been described in the English literature.
References [1] Hirayama K, Toyokura Y, Tsubaki T. Juvenile muscular atrophy of unilateral upper extremity; a new clinical entity. Psychiatr Neurol Jpn 1959;61:2190 – 7. [2] Hirayama K, Tsubaki T, Toyokura Y, Okinaka S. Juvenile muscular atrophy of unilateral upper extremities. Neurology 1963;13:373 – 80. [3] Gourie-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol 1984;41:388 – 94. [4] Peires JB, Seneviratne KN, Wicremasinghe HR, Gunatilake SB, Gamage R. Non-familial juvenile distal spinal muscular atrophy of upper extremity. J Neurol Neurosurg Psychiatry 1989;52:314 – 9. [5] Compernolle T. A case of juvenile muscular atrophy confined to one upper limb. Eur Neurol 1973;102:37 – 42. [6] Serratrice G, Pellissier JP, Pouget J. Etude nosologique de 25 cas d’amyotrophie monomelique chronique. Rev Neurol (Paris) 1987; 143:201 – 10. [7] De Visser M, De Visser BWO, Verbeeten B. Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy. Eur Neurol 1988;28:135 – 8. [8] Gourie-Devi M, Nalini A. Sympathetic skin response in monomelic amyotrophy. Acta Neurol Scand 2001;1:162 – 6. [9] Hirayama K, Tokumara Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 2000;54:1922 – 6. [10] Kira J, Ochi H. Juvenile muscular atrophy of the distal upper limb (Hirayama disease) associated with atopy. J Neurol Neurosurg Psychiatry 2001;6:798 – 801. [11] Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry 1987;50:285 – 90. [12] Tandan R, Sharma KR, Bradley WG, Bevan H, Jacobsen P. Chronic segmental spinal muscular atrophy of upper extremities in identical twins. Neurology 1990;40:236 – 9. [13] Mishra UK, Kalita J. Central motor conduction in Hirayama disease. Electroencephalogr Clin Neurophysiol 1995;97:73 – 6. [14] Robberecht W, Aguirre T, Van den Bosch L, Theys P, Nees H, Cassiman JJ, et al. Familial juvenile focal amyotrophy of the upper extremity (Hirayama disease). Superoxide dismutase genotype and activity. Arch Neurol 1997;54:46 – 50. [15] Sobue I, Saito N, Lida M, Ando K. Juvenile type of distal and segmental muscular atrophy of upper extremities. Ann Neurol 1978; 3:429 – 32. [16] Schlegel U, Jerusalem F, Tachmann W, Cordt A, Tsuda Y. Benign juvenile focal muscular atrophy of upper extremities: a familial case. J Neurol Sci 1987;80:351 – 3. [17] Gucuyener K, Aysun S, Topalogu H, Inan L, Varli K. Monomelic amyotrophy in siblings. Pediatr Neurol 1991;7:220 – 2. [18] Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand 2003;107: 215 – 20. [19] Schroder R, Keller E, Flacke S, Schmidt S, Pohl C, Klockgether T, et al. MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease? J Neurol 1999;246: 1069 – 74.