Online Mendelian Inheritance in Man (OMIM) (original) (raw)

# 182980

SPINAL MUSCULAR ATROPHY, LATE-ONSET, FINKEL TYPE; SMAFK

Alternative titles; symbols

FINKEL LATE-ADULT TYPE SMA

SPINAL MUSCULAR ATROPHY, PROXIMAL, ADULT, AUTOSOMAL DOMINANT

SNOMEDCT: 784391002; ORPHA: 209335; DO: 0111194;

Phenotype-Gene Relationships

TEXT

A number sign (#) is used with this entry because of evidence that the Finkel type of late-onset spinal muscular atrophy (SMAFK) is caused by heterozygous mutation in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; 605704) on chromosome 20q13.

Description

Spinal muscular atrophy is characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and wasting.

See also autosomal recessive adult-onset proximal spinal muscular atrophy (SMA4; 271150), caused by defect in the SMN1 gene (600354), and autosomal dominant childhood-onset proximal SMA (158600).

Clinical Features

Pearn (1978) reported 13 patients from 6 kindreds with autosomal dominant proximal spinal muscular atrophy. Median age at disease onset was 37 years. The authors estimated that 30% of adult onset cases of SMA are due to an autosomal dominant gene. Pearn (1978) suggested that a separate gene was responsible for autosomal dominant SMA with childhood onset (birth to 8 years).

Richieri-Costa et al. (1981) studied 2 kindreds in which 80 members were affected with an autosomal dominant, slowly progressive spinal muscular atrophy of late onset (average 48.8 years). One of the 2 kindreds was first described by Finkel (1962); the second was a black family living in the same region. The neurogenic nature of the disorder was established by electromyography and muscle biopsy. Unusual findings in this disorder were slow loss of muscle strength and progressive proximal atrophy, which started in the legs and later involved the arms; hypoactive or absent deep tendon reflexes; and generalized fasciculations. Adult spinal muscular atrophy usually begins after the third decade of life, and survival for several decades is typical. Emery (1971) cited cases by Tsukagoshi et al. (1965) and Peters et al. (1968).

In a study on the classification and genetics of proximal SMA, Zerres (1989) documented the clinical course of 6 families including 20 patients suffering from an autosomal dominant form. Three families were classified as having the adult-onset form (after age 20 years). The patients showed a benign course, most of them remaining ambulatory 10 to 40 years after clinical onset (Rietschel et al., 1992). Three patients of the other 3 families suffered from the childhood-onset form, with first symptoms before the age of 12 years and walking difficulties throughout life, whereas other members of these families would have been classified as the adult-onset form. The latter had an onset between ages 17 and 28 years and were only moderately handicapped when examined at ages 38 to 60 years. Rietschel et al. (1992) suggested that the great intrafamilial variability in at least some of the families with autosomal dominant SMA is not compatible with the distinction of 2 clinically defined genetic entities.

Mapping

Kausch et al. (1991) performed linkage studies in 4 families with the autosomal dominant form of proximal spinal muscular atrophy. Three of the families met the criteria proposed by Pearn (1978). In a fourth family, affected individuals presented with an unusually mild SMA with muscle cramps (Ricker and Moxley, 1990); see 158400. For the first 3 families taken together and the fourth family taken alone, close linkage to D5S6, where the SMN1 gene is located, was excluded. The authors concluded that autosomal dominant and autosomal recessive forms of SMA are distinct genetic entities.

Molecular Genetics

In 3 families with the Finkel type of late-onset spinal muscular atrophy, Nishimura et al. (2004) identified a heterozygous missense mutation in the VAPB gene (P56S; 605704.0001). They identified the same mutation in another 3 families with ALS8 (608627) and in 1 family in which some patients had typical, and others atypical, ALS. Although it was not possible to link all these families genealogically, haplotype analysis suggested a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have a function in membrane transport. The data suggested that clinically variable motor neuron diseases may be caused by a dysfunction in intracellular membrane trafficking.

See Also:

Meadows et al. (1969)

REFERENCES

1. Emery, A. E. H.The nosology of the spinal muscular atrophies. J. Med. Genet. 8: 481-495, 1971. [PubMed: 4948374] [Full Text: https://doi.org/10.1136/jmg.8.4.481\]
2. Finkel, N.A forma pseudomiopatica tardia da atrofia muscular progressiva heredo-familial. Arquiv. Neuropsiquiatr. 20: 307-322, 1962.
3. Kausch, K., Muller, C. R., Grimm, T., Ricker, K., Rietschel, M., Rudnik-Schoneborn, S., Zerres, K.No evidence for linkage of autosomal dominant proximal spinal muscular atrophies to chromosome 5q markers. Hum. Genet. 86: 317-318, 1991. [PubMed: 1997389] [Full Text: https://doi.org/10.1007/BF00202419\]
4. Meadows, J. C., Marsden, C. D., Harriman, D. G. F.Chronic spinal muscular atrophy in adults. I. The Kugelberg-Welander syndrome. J. Neurol. Sci. 9: 527-550, 1969. [PubMed: 5367043] [Full Text: https://doi.org/10.1016/0022-510x(69)90093-8\]
5. Nishimura, A. L., Mitne-Neto, M., Silva, H. C. A., Richieri-Costa, A., Middleton, S., Cascio, D., Kok, F., Oliveira, J. R. M., Gillingwater, T., Webb, J., Skehel, P., Zatz, M.A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet. 75: 822-831, 2004. [PubMed: 15372378] [Full Text: https://doi.org/10.1086/425287\]
6. Pearn, J.Autosomal dominant spinal muscular atrophy: a clinical and genetic study. J. Neurol. Sci. 38: 263-275, 1978. [PubMed: 712386] [Full Text: https://doi.org/10.1016/0022-510x(78)90072-2\]
7. Peters, H. A., Opitz, J. M., Goto, I., Reese, H. H.The benign proximal spinal progressive muscular atrophies: a clinical and genetical study. Acta Neurol. Scand. 44: 542-560, 1968. [PubMed: 5726730] [Full Text: https://doi.org/10.1111/j.1600-0404.1968.tb05591.x\]
8. Richieri-Costa, A., Rogatko, A., Levisky, R., Finkel, N., Frota-Pessoa, O.Autosomal dominant late adult spinal muscular atrophy, type Finkel. Am. J. Med. Genet. 9: 119-128, 1981. [PubMed: 7258225] [Full Text: https://doi.org/10.1002/ajmg.1320090206\]
9. Ricker, K., Moxley, R. T., III.Autosomal dominant cramping disease. Arch. Neurol. 47: 810-812, 1990. [PubMed: 2357164] [Full Text: https://doi.org/10.1001/archneur.1990.00530070108019\]
10. Rietschel, M., Rudnik-Schoneborn, S., Zerres, K.Clinical variability of autosomal dominant spinal muscular atrophy. J. Neurol. Sci. 107: 65-73, 1992. [PubMed: 1578236] [Full Text: https://doi.org/10.1016/0022-510x(92)90210-c\]
11. Tsukagoshi, H., Nakanishi, T., Kondo, K., Tsubaki, T.Hereditary proximal neurogenic muscular atrophy in adults. Arch. Neurol. 12: 597-603, 1965. [PubMed: 14295959] [Full Text: https://doi.org/10.1001/archneur.1965.00460300045005\]
12. Zerres, K.Klassification und Genetik spinaler Muskelatrophien. Stuttgart: Thieme (pub.) 1989.

Contributors:

Anne M. Stumpf - updated : 10/25/2004
Cassandra L. Kniffin - reorganized : 3/31/2004

Creation Date:

Victor A. McKusick : 6/2/1986

Edit History:

carol : 12/25/2022
carol : 03/20/2015
ckniffin : 2/13/2013
alopez : 10/25/2004
carol : 3/31/2004
ckniffin : 3/31/2004
ckniffin : 3/29/2004
mgross : 3/17/2004
mimadm : 3/25/1995
supermim : 3/16/1992
supermim : 3/20/1990
ddp : 10/27/1989
marie : 3/25/1988
marie : 12/16/1986