Résumé :
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Communication n° 577 Lower Motor Neuron diseases (LMND) form a wide spectrum of rare sporadic and hereditary neuromuscular disorders, characterized by progressive degeneration of the motor neurons of the spinal cord. We reported here the clinical picture of a severe familial childhood onset LMND in a large inbred African pedigree, with autosomal recessive inheritance. Motor milestones were normal in all of the five patients and the first symptoms occurred at the age of 2 to 3,5 years, except in one sibling who felt muscle weakness later, at the age of 11,5 years. At the age of 5 years, most of the patients presented a real Gower's sign, a symmetrical atrophy of scapular muscles, bilateral equinus feet and retracted fingers Facial muscles were preserved. All tendon reflexes were abolished and the diagnosis of motor neuron disease was suspected on neurological assays, showing muscle denervation with normal motor and sensory nerve conduction velocities. Muscle biopsy showed a pattern of denervation and sensory sural nerve was optically normal. Conversely to classical childhood onset spinal muscular atrophies, no predominance of weakness between proximal and distal muscles was noted. The generalized muscle atrophy rapidly worsened and walking ability was lost at the age of 7,5 to 8,5 years, except for one sibling, still ambulant at the age of 20 years. Severe scoliosis with hyperlordosis occurred during childhood and respiratory function progressively decreased, requiring assisted ventilation by tracheotomy at the age of 15 to 17 years. Genetic analysis in this pedigree allowed us to exclude the SMN gene (5q13.3) and to map the causing mutation in a 3,9 centimorgan interval between loci D1S508 and D1S2633 on chromosome 1p36.3 (Zmax=3,79 at locus D1S253). This study broadens the spectrum of hereditary childhood onset LMNDs and opens the way towards the identification of a novel gene involved in motor neuron degeneration.
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