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Spinal muscular atrophy with progressive myoclonic epilepsy

Reviewed December 2013

What is spinal muscular atrophy with progressive myoclonic epilepsy?

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness and wasting (atrophy) and a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy).

In individuals with SMA-PME, spinal muscular atrophy results from a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). After a few years of normal development, affected children begin experiencing muscle weakness and atrophy in the lower limbs, causing difficulty walking and frequent falls. The muscles in the upper limbs are later affected, and soon the muscle weakness and atrophy spreads throughout the body. Once weakness reaches the muscles used for breathing and swallowing, it leads to life-threatening breathing problems and increased susceptibility to pneumonia.

A few years after the muscle weakness begins, affected individuals start to experience recurrent seizures (epilepsy). Most people with SMA-PME have a variety of seizure types. In addition to myoclonic epilepsy, they may have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Affected individuals can also have absence seizures, which cause loss of consciousness for a short period that may or may not be accompanied by muscle jerks. In SMA-PME, seizures often increase in frequency over time and are usually not well-controlled with medication. Individuals with SMA-PME may also have episodes of rhythmic shaking (tremors), usually in the hands; these tremors are not thought to be related to epilepsy.

Some people with SMA-PME develop hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss).

Individuals with SMA-PME have a shortened lifespan; they generally live into late childhood or early adulthood. The cause of death is often respiratory failure or pneumonia.

How common is spinal muscular atrophy with progressive myoclonic epilepsy?

SMA-PME is a rare disorder; approximately a dozen affected families have been described in the scientific literature.

What genes are related to spinal muscular atrophy with progressive myoclonic epilepsy?

SMA-PME is caused by mutations in the ASAH1 gene. This gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in lysosomes, which are cell compartments that digest and recycle materials. Within lysosomes, acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Ceramides have several roles within cells. For example, they are a component of a fatty substance called myelin that insulates and protects nerve cells.

ASAH1 gene mutations that cause SMA-PME result in a reduction of acid ceramidase activity to a level less than one-third of normal. Inefficient breakdown of ceramides and impaired production of its breakdown products likely play a role in the nerve cell damage that leads to the features of SMA-PME, but the exact mechanism is unknown.

Related Gene(s)

Changes in this gene are associated with spinal muscular atrophy with progressive myoclonic epilepsy.

  • ASAH1

How do people inherit spinal muscular atrophy with progressive myoclonic epilepsy?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy?

These resources address the diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy and may include treatment providers.

  • Genetic Testing Registry: Jankovic Rivera syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834569)
  • Muscular Dystrophy Association: Spinal Muscular Atrophy (http://mda.org/disease/spinal-muscular-atrophy/types-of)

You might also find information on the diagnosis or management of spinal muscular atrophy with progressive myoclonic epilepsy in Educational resources (http://www.ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/spinal-muscular-atrophy-with-progressive-myoclonic-epilepsy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about spinal muscular atrophy with progressive myoclonic epilepsy?

You may find the following resources about spinal muscular atrophy with progressive myoclonic epilepsy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for spinal muscular atrophy with progressive myoclonic epilepsy?

  • hereditary myoclonus with progressive distal muscular atrophy
  • Jankovic-Rivera syndrome
  • SMAPME
  • SMA-PME

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about spinal muscular atrophy with progressive myoclonic epilepsy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding spinal muscular atrophy with progressive myoclonic epilepsy?

atrophy ; autosomal ; autosomal recessive ; brainstem ; breakdown ; cell ; ceramides ; distal ; enzyme ; epilepsy ; gene ; hereditary ; inherited ; motor ; myoclonus ; nerve cell ; neurological ; pneumonia ; recessive ; respiratory ; seizure ; sensorineural ; sensorineural hearing loss ; susceptibility ; syndrome ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Dyment D, Sell E, Vanstone M, Smith A, Garandeau D, Garcia V, Carpentier S, Le Trionnaire E, Sabourdy F, Beaulieu C, Schwartzentruber J, McMillan H; FORGE Canada Consortium, Majewski J, Bulman D, Levade T, Boycott K. Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy. Clin Genet. 2013 Oct 25. doi: 10.1111/cge.12307. [Epub ahead of print]. (http://www.ncbi.nlm.nih.gov/pubmed/24164096?dopt=Abstract)
  • Striano P, Boccella P, Sarappa C, Striano S. Spinal muscular atrophy and progressive myoclonic epilepsy: one case report and characteristics of the epileptic syndrome. Seizure. 2004 Dec;13(8):582-6. (http://www.ncbi.nlm.nih.gov/pubmed/15519918?dopt=Abstract)
  • Zhou J, Tawk M, Tiziano FD, Veillet J, Bayes M, Nolent F, Garcia V, Servidei S, Bertini E, Castro-Giner F, Renda Y, Carpentier S, Andrieu-Abadie N, Gut I, Levade T, Topaloglu H, Melki J. Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. Am J Hum Genet. 2012 Jul 13;91(1):5-14. doi: 10.1016/j.ajhg.2012.05.001. Epub 2012 Jun 14. (http://www.ncbi.nlm.nih.gov/pubmed/22703880?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2013
Published: October 20, 2014