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Interpretive Handbook

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Test 81176 :
Spinobulbar Muscular Atrophy (Kennedy Disease), Molecular Analysis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

X-linked spinal and bulbar muscular atrophy (spinobulbar muscular atrophy: SBMA, or Kennedy disease) is characterized by onset of progressive muscle weakness, atrophy, and fasciculations typically in the fourth or fifth decade of life. Affected patients also have signs of androgen insensitivity such as gynecomastia, reduced fertility, and testicular atrophy. The clinical severity and age at onset can be quite variable, even within families. Because this is an X-linked disease, males manifest this disorder and females are generally asymptomatic carriers. However, there have been reports of female carriers who exhibit symptoms such as muscle weakness and cramping.

 

SBMA is caused by an expansion of the CAG trinucleotide repeat in exon 1 of the human androgen receptor (AR) gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 11 to 34. The number of repeats found in affected individuals can range from 38 to 62. There is no consensus as to the clinical significance of alleles of 35 CAG repeats and literature suggests that alleles of 36 to 37 CAG repeats may be associated with reduced penetrance. As with other trinucleotide repeat disorders, anticipation is frequently observed and larger CAG expansions are associated with earlier onset and a more rapid clinical progression.

Useful For Suggests clinical disorders or settings where the test may be helpful

Molecular confirmation of clinically suspected cases of sporadic or familial spinobulbar muscular atrophy (SBMA)

 

Presymptomatic testing for individuals with a family history of SBMA and a documented expansion in the androgen receptor (AR) gene

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

For predictive testing, it is important to first document the presence of a CAG-repeat amplification in the androgen receptor (AR) gene in an affected family member to confirm that molecular expansion is the underlying mechanism of disease in the family.

 

We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.

 

Predictive testing of an asymptomatic child is not recommended.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

 

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Current evidence suggests that the majority of individuals with spinobulbar muscular atrophy have a CAG-repeat expansion. However, we cannot eliminate the possibility that another type of mutation not detected by our assay is present within the AR gene.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Normal alleles: 11-34 CAG repeats

Abnormal alleles: 36-62 CAG repeats

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

Pinsky L, Beitel LK, Trifiro MA: Spinobulbar muscular atrophy. In The Metabolic and Molecular Basis of Inherited Disease. Vol 4. Eighth edition. Edited by CR Scriver. AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 4147-4157


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