Autosomal dominant congenital spinal muscular atrophy – A possible developmental deficiency of motor neurones?

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Abstract

We describe a kindred with an unusual congenital lower motor neuron disorder with significant but static muscle weakness predominantly affecting the lower limbs. The proband had talipes equinovarus and congenital hip contractures and did not walk until 19 months of age. Lower-extremity predominant, primarily proximal weakness was identified on assessment at three years. Over a 20 year follow-up there has been no clinical progression. The proband has a four-year-old daughter with very similar clinical findings. Electromyography and muscle biopsy suggest reduced numbers of giant normal duration motor units with little evidence of denervation or reinnervation.

Dominant congenital spinal muscular atrophy predominantly affecting the lower limbs is rarely described. It is possible that the disorder is due to a congenital deficiency of motor neurons.

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Case report

The proband was born at term after an uncomplicated pregnancy with bilateral hip subluxation and talipes equinovarus. She was treated with traction and orthoses. She had floppy weak legs and early delay of her motor milestones. She crawled at 14 months and walked at 19 months of age. She had bladder and bowel dysfunction, with urinary urgency, persisting urinary and faecal incontinence and recurrent urinary tract infections. Her fine motor development and speech and language acquisition were

Discussion

This family has an autosomal dominant disorder with weakness in both proximal and distal muscles, more in the lower than the upper limbs, and sparing the cranial musculature, which is apparent from birth and is associated with arthrogryposis suggesting in utero onset, yet has remained static through to adult life. The genetic basis of this condition is unknown.

A number of other reports have described isolated cases and/or kindreds with presumed dominant inheritance of congenital lower limb

Acknowledgements

The authors thank Dr. Arun Aggarwal for performing the MUNE studies; Professors John Pollard, Clive Harper and Roger Pamphlett for recutting and reviewing the muscle biopsy; Dr. Ponmailainathan Ketheswaran for the MRI imaging and review of the anatomy; and Dr. Kevin Talbot for a critical review of the manuscript.

The study was supported by the University of Antwerp, the Fund for Scientific Research (FWO-Flanders), the American Muscular Dystrophy Association (MDA), and the Interuniversity

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