Axonal Neuropathy and Predominance of Type II Myofibers in Infantile Spinal Muscular Atrophy

Abstract

Two affected siblings with infantile spinal muscular atrophy (SMA I) presented with generalized muscular hypotonia, which progressed to early death. Quadriceps muscle biopsy did not show the typical neurogenic pattern of spinal muscular atrophy. The histochemical fiber type determination revealed a predominance of type II fibers without type I hypertrophy, an unprecedented finding in spinal muscular atrophy. Sural nerve biopsy exhibited findings typical for axonal neuropathy. In one patient, electrical stimulation of peripheral nerves showed an inexcitability of motor and sensory nerves. Genetic studies revealed homozygous deletions of the telomeric survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene in the affected children. This is the second case report of molecular genetically proven spinal muscular atrophy associated with axonal neuropathy. We conclude atypical findings on muscle biopsy and evidence of axonal neuropathy are compatible with the diagnosis of infantile spinal muscular atrophy. (J Child Neurol 1998;13:327-331).

Get full access to this article

View all access options for this article.

References

Munsat TL , Davies KE : International SMA Consortium Meeting, June 26-28, 1992, Bonn, Germany. Neuromusc Disord 1992;2: 423-428.

Wirth B. , Rudnik-Schöneborn S. , Hahnen E. , et al: Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11. 2-q13.3): Molecular genetics and experience in 109 cases. Prenat Diagn 1995;15:407-414.

Lefebvre S. , Bürglen L. , Reboullet S. , et al: Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995;80:155-165.

Roy N. , Mahadevan MS , McLean M. , et al: The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 1995;80:167-178.

Rudnik-Schöneborn S. , Forkert R. , Hahnen E. , et al: Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: Further delineation on the basis of SMN gene deletion findings. Neuropediatrics 1996;27:8-15.

Korinthenberg R. , Sauer M. , Ketelsen UP , et al: Congenital axonal neuropathy caused by deletions in the spinal muscular atrophy region. Ann Neurol 1997;42:364-368.

Gutrecht JA , Dyck PJ : Quantitative teased-fiber and histologic studies of human sural nerve during postnatal development. J Comp Neurol 1970;138:117-130.

Jacobs JM , Love S. : Qualitative and quantitative morphology of human sural nerve at different ages. Brain 1985;108:897-924.

Schröder JM , Bohl J. , Brodda K. : Changes of the ratio between myelin thickness and axon diameter in the human developing sural nerve. Acta Neuropathol 1978 ;43:169-178.

10.

Schröder JM , Bohl J. , von Bardeleben U. : Changes of the ratio between myelin thickness and axon diameter in human developing sural, femoral, ulnar, facial, and trochlear nerves. Acta Neuropathol 1988; 76:471-483.

11.

Hahnen E. , Forkert R. , Marke C. , et al: Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: Evidence of homozygous deletions of the SMN gene in unaffected individuals. Hum Mol Genet 1995;4:1927-1933.

12.

Wirth B. , Hahnen E. , Morgan K. , et al: Allelic association and deletions in autosomal recessive proximal spinal muscular atrophy: Association of marker genotype with disease severity and candidate cDNAs. Hum Mol Genet 1995;4:1273-1284.

13.

Pearn JH , Wilson J. : Acute Werdnig-Hoffmann disease: Acute infantile spinal muscular atrophy . Arch Dis Child 1973;48:425-430.

14.

Renault F. , Chartier JP , Harpey JP : Apport de l'électromyogramme au diagnostic d'amyotrophie spinale infantile en période néonatale. Arch Pediatr 1996;3:319-323.

15.

Buchino JJ , Bove KE , Iannaccone ST : Transient cytoplasmic bodies in muscle of three infants with Werdnig-Hoffmann disease. Pediatr Pathol 1990;10:563-573.

16.

Kingma DW , Feeback DL , Marks WA , et al: Selective type II muscle fiber hypertrophy in severe infantile spinal muscular atrophy. J Child Neurol 1991 ;6:329-334.

17.

Malamud N. : Infantile progressive muscular atrophy, in Minckler J (ed): Pathology of the Nervous System. New York, McGraw-Hill, 1968, pp 725-732.

18.

Marshall A. , Duchen LW : Sensory system involvement in infantile spinal muscular atrophy. J Neurol Sci 1975;26:349-359.

19.

Murayama S. , Bouldin TW , Suzuki K. : Immunocytochemical and ultrastructural studies of Werdnig-Hoffmann disease. Acta Neuropathol 1991;81:408-417.

20.

Melki J. , Lefebvre S. , Bürglen L. , et al: De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science 1994;264:1474-1477.