Atrophy of the bulbospinal muscles, Choroba Kennedy’ego
Spino-bulbar muscular atrophy (SBMA, MIM 313200) is a rare neurodegenerative disease with recessive, sex-linked inheritance. Although this syndrome belongs to the group of spinal muscular atrophy, due to the coexistence of endocrine disorders, it requires separate discussion.
The prevalence of SBMA is estimated at 1 in 50 people in the population. In Scandinavian countries and Japan, the incidence of SBMA is higher. In the course of the disease, there are neurological symptoms accompanied by hormonal disorders. Due to recessive, sex-linked inheritance, males suffer and females are carriers of the mutation.
This syndrome was first described by Kennedy in 1968. In classic descriptions, the syndrome consists mainly of muscle weakness and atrophy, mainly muscle weakness, bulbar symptoms, fasciculations and gynecomastia. However, the course of the disease can be very diverse – from asymptomatic increases in phosphocreatine kinase activity, to severe weakening of muscle strength, with loss of the ability to walk independently and respiratory failure.
The age of onset of SBMA is usually in the range of 15-60 years, most often it is 3-4. a decade of life. The oldest patient described in the literature, whose diagnosis was confirmed by genetic testing, fell ill at the age of 83. The patient reported painful calf cramps and general fatigue.
According to recent studies summarizing large groups of respondents, the earliest observed symptom is hand tremor, which usually occurs around the age of 30. Other early symptoms include muscle aches, fatigue, painful calf cramps, and fasciculations. For several to several years, these symptoms precede the weakening of muscle strength. The weakness initially affects primarily the muscles of the lower limbs (over 70% of patients), causing difficulties in walking up stairs, getting up from a sitting position, and overcoming long distances. Less often, paresis of the muscles of the upper limbs appears first, with more frequent involvement of the distal muscles. In a small percentage of patients, articulation disorders are the initial symptom of muscle weakness.
On neurological examination, in addition to muscle weakness and atrophy, most patients exhibit clinically discrete abnormal sensation. Deep reflexes, especially knee reflexes, are weakened or suppressed. However, no pyramidal or cerebellar symptoms or sphincter disorders are observed. There are also many hormonal disorders in the course of SBMA, which are a symptom of androgen insensitivity. The main symptom is gynecomastia, which is often asymmetrical. It may appear many years before the onset of neurological disorders and be the first symptom of the disease (Fig. 16.1). Apart from gynecomastia, in the course of SBMA, libido disorders, impotence and infertility are also observed. These symptoms usually appear in the advanced stages of the disease. The sick usually start families and have children. Some patients also have other metabolic disorders – type 2 diabetes and hypercholesterolaemia.
In addition to the symptoms listed above, some authors point out neurotic disorders, depression, and memory disorders in patients with SBMA. It is difficult to assess whether they are a reaction to a chronic and incurable disease, or if they are part of the clinical picture of SBMA. Taking into account the hormonal disorders in patients, these changes may be the result of both of the above factors.
The disease progresses slowly. Over time, neurological symptoms, metabolic and hormonal complications increase. Weakness and muscle wasting worsen. Bulbar symptoms (dysarthria, dysphagia) appear. After 30-40 years of the disease, the ability to walk independently may occur. The survival time of SBMA patients usually does not differ from the average in the population. The most frequently reported cause of death is aspiration pneumonia. However, there have been reports of a violent course in which immobilization occurred after several years of the disease. Anticipation is not usually found in SBMA families. However, there is intra-family variability in the age of onset and severity of clinical symptoms.
Carriers of the mutation usually do not exhibit clinical symptoms, although calf cramps and fasciculations may appear. Sometimes discrete distal muscle weakness and an increase in keratin kinase activity are observed. As a rule, these ailments appear late, at 7-8 years. decade of life.
Source: M. Jędrzejowska, Neuromuscular diseases; Czelej Publishing House