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Year : 2010  |  Volume : 58  |  Issue : 4  |  Page : 665--666

Bethlem myopathy: A study of two families

A Nalini1, N Gayathri2,  
1 Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India
2 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India

Correspondence Address:
A Nalini
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore
India




How to cite this article:
Nalini A, Gayathri N. Bethlem myopathy: A study of two families.Neurol India 2010;58:665-666


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Nalini A, Gayathri N. Bethlem myopathy: A study of two families. Neurol India [serial online] 2010 [cited 2021 Oct 17 ];58:665-666
Available from: https://www.neurologyindia.com/text.asp?2010/58/4/665/68684


Full Text

Sir,

We report two families of Bethlem myopathy with three affected members. Clinical phenotypes were defined according to the classification proposed by the European Neuromuscular Center Bethlem Consortium. [1]

Family I:

In the first family two members, father aged 38 years and his daughter aged 10 years were affected. The daughter had history of low birth weight and delayed cry and in early childhood had developed hip, shoulder, knee, and ankle contractures. At 3 years of age she was able to walk short distances independently. She had proximal muscle weakness of both upper and lower limbs and was ambulant till the age of 9 years. She had subsequent deterioration, and became wheelchair bound by 10 years of age. She had no history of cardiac or respiratory symptoms. Examination of the proband revealed normal intelligence, and facial and bulbar muscles were normal. She had a thin slender habitus, with severe contractures at the shoulders, elbows, hips, knees, ankles, and spine. She had a rigid spine and there was distal hyperextensibility at the interphalangeal joints, wrist, and toes [Figure 1]d and e. Palms and soles showed absence of the major palmar and plantar creases and there were abnormal mesh-like creases. The motor power was grade 2-3/5 in the proximal and distal muscles. All deep tendon reflexes were absent.{Figure 1}

Birth and early developmental history of the father was normal. milestones were normal. At 7 years of age he had developed progressive contractures at the elbows, hips, knees, and ankles, with proximal muscle weakness in the lower limbs. By 13 years of age he was unable to stand and adopted a permanent squatting position though he could move independently [Figure 1]c; this disbility has remained unchanged. He had no distal muscle weakness. During adolescence he had undergone acupuncture therapy and developed keloids at all the acupuncture sites. There were no cardiac or respiratory symptoms. Examination revealed multiple keloids [Figure 1]b and prominent contractures of proximal [Figure 1]a and distal joints, with moderate wasting of shoulder girdle muscles. Power was grade 4/5 in the upper limbs and 4/5 in the lower limbs. There was no hyperlaxity of the distal joints. Palmar and plantar creases were normal. Deep tendon reflexes were normal in the upper limbs and sluggish in the lower limbs.

Creatine kinase (CK) levels were 295 IU/l and 185 IU/l in the father and daughter, respectively and electromyography (EMG) showed myopathic features. In the both electrocardiography (ECG) and 2D echocardiogram were normal in both. Muscle biopsy in the girl was performed at another institute at the age of 7 years and was reported as showing dystrophic changes. The father's biceps muscle biopsy showed dystrophic features.

Family II:

In the second family, a 10-year-old girl had symptoms of progressive contractures of joints since the age of 2 years. In early childhood, she developed difficulty in running and had motor disability due to contractures, with difficulty in folding her legs, extending her elbows, and performing fine work with her fingers. Her symptoms were gradually progressive or stationary, with no worsening in motor weakness or the disability. Her mental functions were normal. Examination revealed prominent contractures at the elbows, wrist, fingers, hips, knees, and ankles [Figure 2]a and b, with moderate wasting of the distal muscles of the upper and lower limbs. There was mild weakness of grade 4/5 in the proximal and distal muscles. All deep tendon reflexes were sluggish. Her younger sibling aged 2 years had had a normal birth, developmental milestones were normal and she had multiple contractures at the elbows, knees, and ankles. There were no finger contractures. Muscle power and deep tendon reflexes were normal. The CK value was 84 IU/l and 291 IU/l in the siblings respectively. EMG showed a myopathic process. ECG and 2D echocardiogram were normal. Biceps muscle biopsy revealed mild dystrophic features.

Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by congenital hypotonia, muscular weakness, joint contractures, and myopathic or dystrophic changes on muscle histopathology. [2] Only two disorders manifest with a combination of contractures and hyperlaxity of joints: most commonly, Ullrich disease, and to a milder extent, Bethlem myopathy. [2] Bethlem myopathy is a childhood-onset, relatively benign, disorder that manifest with contractures and limb girdle muscle weakness. [3] Clinical onset can be prenatal, when it manifests with reduced fetal movements, or it may be neonatal, manifesting with hypotonia; most often, however, it occurs in childhood or early adulthood and, in some cases, as late as in the sixth decade. [3]{Figure 2}

The hallmark of Bethlem myopathy is long finger flexion contractures. [4] The father had multiple keloids at all sites of acupuncture, which is an unusual skin manifestation that has been classically described in Bethlem myopathy. [3] Mutations in the genes coding for the three subunits of collagen VI: COL A1/A2 on chromosome 21q 22.3 and COL A3 on chromosome 2q 37 have been demonstrated. [1],[5],[6] The collagen VI protein is a major component of the extracellular matrix. Complete loss or reduction of collagen VI occurs in this disorder. [6]

References

1Pepe G, de Visser M, Bertini E, Bushby K, Vanegas OC, Chu ML, et al. Bethlem myopathy(BETHLEM) 86 th ENMC International workshop, 10-11 November 2000, Naarden, the Netherlands. Neuromuscul Disord 2002;12:296-73.
2Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet 2005;42:673-85.
3Bethlem J, Wijngaarden GK. Benign myopathy, with autosomal dominant inheritance. A report on three pedigrees. Brain 1976;99:91-100.
4Merlini L, Morandi L, Granata C, Ballestrazzi A. Bethlem myopathy: early onset benign autosomal dominant myopathy with contractures: description of two new families. Neuromuscul Disord 1994;4:502-11.
5Tetreault M, Duquette A, Thiffault I, Bherer C, Jarry J, Loisel L, et al. A new form of congenital muscular dystrophy with joint hyperlaxity maps to 3p23-21. Brain 2006;129:2077-84.
6Ishikawa H, Sugie K, Murayama K, Awaya A, Suzuki Y, Noguchi S, et al. Ullrich disease due to deficiency of collagen VI in the sarcolemma. Neurology 2004;62:620-3.