Spinal and bulbar muscular atrophy
The spinobulbar muscular atrophy type Kennedy ( SBMA ), also known as Kennedy 's disease, is a rare X-linked recessive hereditary disease from the group of Trinukleotiderkrankungen. It is a special form of hereditary spinal muscular atrophy. The Kennedy 's disease is to be distinguished from the Foster Kennedy syndrome, which is often just called Kennedy's disease, which is a completely different disease.
Description
The SBMA is a slowly progressive ( progressive ) neuromuscular disease. The degeneration of the lower motor neurons leads to hypotonia (muscle weakness), muscle atrophy ( muscle wasting) and fasciculations ( involuntary movements, " twitching ", very small muscle groups). From the muscle weakness and muscle atrophy especially the hüftnahe leg muscles, the shoulder girdle and the face, tongue and throat muscles are affected, the symptoms may begin in one of these areas and progress over years to decades. The fasciculations typically occur on the extremities and muscles of facial expression. Due to the deterioration of the tongue and throat muscles during speech disorder ( dysarthria ) and swallowing difficulties may arise. The ability to walk is a long time.
Due to the X- chromosomal inheritance only men are affected by the disease. Many patients also have gynecomastia (enlargement of the mammary gland ) and testicular atrophy ( shrinking testicles). Fertility is significantly reduced by the androgen insensitivity. Gynecomastia or male infertility may well represent the first symptom.
In contrast, ill women who carry the gene defect is heterozygous, not. Enter the disease with a 50 - % probability on to their male offspring. The sons of affected fathers, however, are always healthy, because they carry the maternal X chromosome. In statistically very rare case of homozygosity of the defective AR gene in women - that is, both parents carried the defect in the AR gene - the symptoms in the affected patients make significantly weaker than in heterozygous male SBMA patients.
As a rule, the SBMA between 20 and 40 years manifested. The life expectancy of patients is - in contrast to the related amyotrophic lateral sclerosis ( ALS) and most other forms of spinal muscular atrophy - normal. A differential diagnosis to other forms of motor € diseases is therefore important.
Prevalence and diagnosis
In Europe, the prevalence of 1:36.000 is assumed. However local they may be significantly higher. In the Finnish region of Vaasa for example, a prevalence of 1:6500 was found. Based on the analysis of genetic data, it is assumed that the SBMA about 20 generations in the first time, occurred West Finland. The analysis of the haplotype suggesting a common ancestor for most Scandinavian SBMA patients.
Even before muscular degeneration can be detected, the SBMA manifested - due to the peripheral androgen - by Gynecomastia. The SBMA can molecular diagnostic sure about the number of CAG repeats in the androgen receptor gene on the X chromosome - be detected - even prenatally.
Etiology and Genetics
The spinobulbar muscular atrophy is caused by a Trinukleotidexpansion in the AR gene coding for the androgen receptor. Affected is the exon 1 While healthy people 10-36 repeating units CAG (cytosine, adenine, and guanine) that encode the amino acid glutamine, have in their genome, can be found in SBMA patients 38-62 of these units the polyglutamine form. The affected gene is on the X chromosome gene locus q11 - q12. So far, no clear correlation between the severity of the disease and the number of repetitive CAG units could be detected. In contrast, a slight correlation between the chain length of the poly-glutamic acid and the age at Krankheitsausbrauch was (longer chain leads to earlier disease ) was observed.
Therapy
There is not yet an effective treatment of Spinobulbären muscular atrophy. Various therapeutic approaches to the administration of androgens are currently being investigated. In animal models show different substances, for example, a histone deacetylase inhibitor ( HDAC1 ), leuprorelin and a curcumin derivative, a potential efficacy. But Regulatory approval of proven efficacy toward medication, it takes experience, for many years.
First description
The Kennedy 's disease is named after the American neurologist William R. Kennedy, of the SBMA in 1968 described together with two colleagues. Before Kennedy may already described four Japanese authors, the SBMA. In 1991, the molecular genetic cause of the disease was determined by an increased number of CAG units in exon 1 of the affected AR gene.