Sleep disorders in spinal and bulbar muscular atrophy kennedys disease. To test the hypothesis that serum creatinine crn could be a prognostic biomarker for monitoring progression of denervation in patients with sma, we determined whether serum crn concentration correlates with disease severity in. Distal spinal muscular atrophy type v dsmav spinal muscular atrophy with lower extremity predominance smaled having a single faulty copy of a gene is enough to cause the condition, even though a healthy copy of the gene is also present. This type of sma, also known as kennedys disease, is quite different from the chromosome 5 type. Kennedys disease, also known as bulbospinal muscular atrophy bsma, is a rare xlinked. May, 2020 spinal and bulbar muscular atrophy is an xlinked motor neuron disease caused by a cag repeat expansion in the androgen receptor gene. Spinal and bulbar muscular atrophy sbma, or kennedys disease, is a. Spinal and bulbar muscular atrophy clinical features and pathogenesis clinical features sbma, or kennedys disease, is an inherited lower motor neuron disease characterised by adultonset muscle atrophy, weakness, contraction, fasciculations, and bulbar involvement1,2. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption.
Dysphagia develops after 10 years of muscle weakness, followed by the need of a. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 140160. What is spinal muscular atrophy definition spinal muscular atrophy sma is a severe, autosomal recessive neuromuscular disease that affects 1 in 8000 to 1 in 10,000 people. Spinal muscular atrophy sma is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Spinal muscular atrophy type i is the most common type, accounting for about half of all cases. Lieberman,1, zhigang yu,1 sue murray,2 raechel peralta,2 audrey low,2 shuling guo,2 xing xian yu,2 constanza j.
Spinal and bulbar muscular atrophy is an xlinked motor neuron disease caused by a cag repeat expansion in the androgen receptor gene. Spinal and bulbar muscular atrophy sbma, or kennedys disease, is a hereditary neuromuscular disease characterized by muscle atrophy, weakness, dysarthria, and dysphagia. Aac amyotrophic lateral sclerosis duchenne muscular dystrophy myotonic muscular dystrophy spinal muscular atrophy communication assistive technology key points augmentative and alternative communication aac is considered standard practice in interventions for individuals with progressive neuromuscular disease. Mar 12, 2014 spinal muscular atrophy is characterised by slowly progressive muscle weakness and atrophy of the limb muscles associated with motor neurone loss in the spinal cord.
Spinal and bulbar muscular atrophy sbma, or kennedys disease is an inherited, adultonset degenerative disease of lower motor neurons in the brain stem and spinal cord. Spinal and bulbar muscular atrophy sbma, kennedys disease is an xlinked, adult onset motor neuron disease characterized by slowly progressive weakness of the bulbar and extremity muscles. Spinal and bulbar muscular atrophy mainly affects males and is. Spma goes under in many names, kennedys disease, xlinked spinal muscular atrophy type 1, xlinked spinal and bulbar muscular atrophy, spinal bulbar muscular atrophy, and spinal and bulbar muscular atrophy just to name some. All generally result in worsening muscle weakness associated with muscle twitching. These nerve cells originate in the spinal cord and the part of the brain that is connected to the spinal cord the brainstem. Mechanisms of pathogenesis and molecular targets in spinal. Spinal and bulbar muscular atrophy sbma kennedys disease. The symptoms of sma and when they first appear depend on the type of sma you have. Feeding and swallo wing problems, dysphagia, bulbar function, spinal muscular atrophy. In regards to the diagnosis of spinal and bulbar muscular atrophy, the ar xq12 gene is the focus. Kennedys disease comes from the name of the neurologist that described the disease in the late 60s.
Kennedy disease le portail hal sorbonne universite. Although ligand testosteronedependent mutant ar aggregation has been shown to play important roles in motor neuronal degeneration by the analyses of transgenic mice models and in vitro cell culture models, the underlying. Keywords spinal and bulbar muscular atrophy sbma insulin resistance insulin receptor introduction spinal and bulbar atrophy sbma is a hereditary neuro muscular disease characterized by slowly progressive muscle atrophy and weakness 1, 2. Both motoneurons and muscles are affected by kd, but where mutant ars act to initiate this disease is not clear. The severity of symptoms and age of onset varies by the type. Spinal and bulbar muscular atrophy pubmed central pmc. Most research is performed on fruit flies and mice models. Sbma is caused by the expansion of a cag repeat within the first exon of the androgen receptor ar gene. Spinal and bulbar muscular atrophy, also known as kennedy disease, is a disorder of specialized nerve cells that control muscle movement motor neurons. Serum creatinine is a biomarker of progressive denervation.
Signs and symptoms of progressive bulbar palsy include difficulty swallowing, weak jaw and facial muscles, progressive loss of speech, and weakening of the tongue. We conducted openended interviews with 21 adult men with genetically confirmed sbma. Amyotrophic lateral sclerosis what is amyotrophic lateral sclerosis als. Spinal muscular atrophy affects 1 per 8,000 to 10,000 people worldwide. Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting atrophy that usually begins in adulthood and worsens slowly over time. Spinal and bulbar muscular atrophy sbma, or kennedys disease, is a slowly progressive lower motor neuron and muscular disease characterized by bulbar and limb muscle weakness and elevated levels of serum creatine kinase. Affected males typically develop weakness in their mid40s as well as evidence of androgen insensitivity with reduced fertility and gynecomastia. Spinal and bulbar muscular atrophy medical condition. Signs and symptoms depend on the type of spinal muscular atrophy, but may include hypotonia, tremors, impaired breathing, and abnormal gait. Spinal muscular atrophy cde revision history document version 2. Spinal and bulbar muscular atrophy, or kennedy disease, is a slowly progressive xlinked neuromuscular disease caused by a trinucleotide cag repeat expansion in the androgen receptor gene.
Apr 26, 2015 spinal and bulbar muscular atrophy, also known as spinobulbar muscular atrophy, bulbo spinal atrophy, xlinked bulbospinal neuropathy, xlinked spinal muscular atrophy type 1, and kennedys. This study enrolled 47 genetically confirmed patients with sbma and 38 age and sexmatched healthy controls. This means that parents with the condition can pass it directly to their children. Spinal muscular atrophy sma is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle. Spinal and bulbar muscular atrophy sbma is an adultonset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. Affected individuals often show gynecomastia, testicular atrophy, and reduced fertility as a result of mild androgen insensitivity. For more information, visit the project page, where you can join the project andor contribute to the discussion. Spinalbulbar muscular atrophy sbma is a genetic disorder in which loss of motor neurons nerve cells in the spinal cord and brainstem affects the part of the nervous system that controls voluntary muscle movement.
Clinical features of spinal and bulbar muscular atrophy brain. Manual muscle testing mmt is commonly used to describe muscle. Spinal and bulbar muscular atrophy is a cag repeat disorder characterized by degeneration of the neuromuscular system that is caused by the polyglutamine androgen receptor polyq ar. Pdf swallowing markers in spinal and bulbar muscular atrophy. Its a serious condition that gets worse over time, but there are treatments to help manage the symptoms. Molecular mechanisms and therapeutics for sbmakennedys. Tongue pressure as a novel biomarker of spinal and bulbar. Aug 25, 2018 spinal muscular atrophy 1 sma1, also known as werdnig hoffmann disease, is a genetic neuromuscular disorder that affects the nerve cells that control voluntary muscles motor neurons. The nuclear accumulation of mutant ar is central to the pathogenesis of sbma. Spinal and bulbar muscular atrophy sbma, also known as kennedys disease, is a rare, xlinked hereditary lower motor neuron disease, characterized by progressive muscular weakness.
Objective identifying simple biomarkers that can predict or track disease progression in patients with spinal muscular atrophy sma remains an unmet clinical need. Spinal muscular atrophy 1 genetic and rare diseases. The primary efficacy end point was the change from baseline of the walking distance covered in 6 minutes at 12 months. Spinal and bulbar muscular atrophy sbma is a slowly progressive motor neuron disease. Spinal and bulbar muscular atrophy sbma, also known as kennedys disease kd. Correlation of insulin resistance and motor function in. Spinal and bulbar muscular atrophy sbma, also known as kennedys disease. Until recently, human tissue was not available for testing in research labs. The disease is caused by the expansion of a cagglutamine tract in the aminoterminus of the androgen receptor. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. Spinal and bulbar muscular atrophy sbma is an adult form of xlinked motor neuron disease caused by an expansion of a cag repeat sequence in the first exon of the androgen receptor ar gene. A randomized controlled trial of exercise in spinal and. Less than 1in40,000 people have the defective gene. Spinal and bulbar muscular atrophy sbma is an adultonset motor neuron disease, caused by the expansion of a trinucleotide repeat tnr in exon 1 of the androgen receptor ar gene.
Spinal bulbar muscular atrophy a type of sma thats usually called sbma, for spinal bulbar muscular atrophy, stems from a gene defect on the x chromosome. The incidence of spinal muscular atrophy ranges from 4 to 10 per 100,000 live births, and the carrier frequency of diseasecausing smn1 mutations ranges from 190 to 147. Spinalbulbar muscular atrophy sbma top level muscular. Objectivespinal and bulbar muscular atrophy sbma is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor ar. Kennedy disease genetic and rare diseases information. Bulbar and spinal muscular atrophy bsma is an adult. A myotrophic lateral sclerosis als is a rare neurological disease that affects nerve cells neurons in the brain and spinal cord that control voluntary muscle movement. Spinal and bulbar muscular atrophy clinical features and.
The documents contained in this web site are presented for information purposes only. Kennedy disease kd, or spinal and bulbar muscular atrophy is caused by a cagpolyglutamine expansion in the androgen receptor ar gene. Especially affected are the facial and swallowing muscles, and the arm and leg muscles, particularly those nearest the. The condition mainly affects males, with onset between the ages of 30 and 60. Clinical presentation muscle weakness involving limbs, respiratory system and bulbar muscles. Augmentative and alternative communication for people with. Spinal bulbar muscular atrophy sbma is an adultonset, slowly progressive motor neuron disease caused by abnormal cag repeat expansion in the androgen receptor ar gene. Decreased peak expiratory flow associated with muscle fiber. Xlinked spinal and bulbar muscular atrophy kennedys disease. May 29, 2019 the spinal muscular atrophies smas comprise a group of autosomalrecessive disorders characterized by progressive weakness of the lower motor neurons. Sma is the most common monogenic cause of infant mortality 23. Nonneural phenotype of spinal and bulbar muscular atrophy. Spinal and bulbar muscular atrophy mainly affects males and is characterized by muscle weakness and wasting atrophy.
Identified impact of symptoms in spinal and bulbar. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in sbma. In both groups we measured tongue pressure using an. Spinal and bulbar muscular atrophy sbma is a neuromuscular disease caused by polyglutamine polyq expansion in the androgen receptor ar. Spinal and bulbar muscular atrophy is an xlinked motor neuron disease caused by a cag repeat expansion in the androgen. Spinal and bulbar muscular atrophy sbma is a neuromuscular disorder with degeneration of lower motor neurons and muscle resulting in slowly progressive weakness, atrophy, and fasciculations. The bulbar muscle involvement in sbma can be significant, affecting speech, chewing and.
Spinal muscular atrophy sma is a group of neuromuscular disorders that result in the loss of motor neurons and progressive muscle wasting. Muscle wasting in the arms and legs results in cramping. Spinal muscular atrophy genetics home reference nih. Spinal and bulbar muscular atrophy may share mechanistic features with other disorders caused by polyglutamine expansion, such as huntingtons disease. Spinal and bulbar muscular atrophy is within the scope of wikiproject disability. Spinal and bulbar muscular atrophy sbma is an xlinked neuromuscular disorder caused by polyglutamine repeat expansion in the androgen receptor. However, many sings are common to sbma and amyotrophic lateral sclerosis als, and sbma patients are sometimes diagnosed with als. Spinal bulbar muscular atrophy, aka kennedys disease, is considered a rare disorder.
A trinucleotide cag repeat expansion in the androgen receptor ar gene on the x chromosome is the cause. Spinal muscular atrophies smas are a genetically and clinically heterogeneous group of rare debilitating disorders characterised by the degeneration of lower motor neurons neuronal cells situated in the anterior horn of the spinal cord and subsequent atrophy wasting of various muscle groups in the body. Bulbar and spinal muscular atrophy kennedys disease. The clinical hallmarks of the disorder are symmetric muscle weakness and atrophy of limb muscles with variable bulbar involvement and tremor and supporting electrophysiologic and. Background spinal and bulbar muscular atrophy sbma is an adultonset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Information was collected from scientific articles published in the last 2 decades, retrieved from the databases scielo, pubmed, and medline. Spinalbulbar muscular atrophy sbma mostly affects men and usually begins between the ages of 30 and 50, although symptoms have begun in boys as young as 15 or men as old as 60. Genetic testing of a cag trinucleotide repeat in the androgen receptor gene confirms the diagnosis. Swallowing markers in spinal and bulbar muscular atrophy. Only some patients with bulbar and spinal muscular atrophy may develop cardiac disease. Some types are apparent at or before birth while others are not apparent until adulthood. Without treatment, symptoms of sma1 become apparent before 6 months of age and include worsening muscle weakness and poor muscle tone hypotonia due to loss.
Unveiling synapse pathology in spinal bulbar muscular atrophy. Jul 29, 2015 progressive bulbar palsy involves the brain stem. January 2020 revisions general core crf updated to replace gender question with sex assigned at birth and gender identity. Both of these diseases are comparatively frequent, with an annual incidence of 3 per 100,000 reported for als and a frequency of one in 10,000 live births observed for sma.
The inheritance patterns of some rarer forms of spinal. Pdf clinical features of spinal and bulbar muscular. This study describes symptoms from the patients perspective and the impact these symptoms have on qol. Spinal and bulbar muscular atrophy sbma, popularly known as kennedys disease, is a progressive debilitating neurodegenerative disorder resulting in muscle cramps and progressive weakness due to degeneration of motor neurons in the brainstem and spinal cord. Spinal muscular atrophy sma is a lower motor neuron disorder characterized by degeneration of the anterior horn cells in the spinal cord and bulbar motor nuclei. Spinal and bulbar muscular atrophy sbma new york clients tests displaying the status new york approved.
Its worth knowing which disorder affects you or your family member, since als is a much more profound and rapidly progressing condition than sbma. Sbma patients may become wheelchair dependent 2030 years after onset tsukagoshi et al. Pdf a mouse model of spinal and bulbar muscular atrophy. Original article convenient diagnosis of spinal and bulbar. Analysis of inconsistencies in terminology of spinal and. Kennedy disease is a gradually progressive, neuromuscular disorder characterized by wasting of the proximal muscles those closer to the trunk and bulbar muscles those of the face and throat.
Bulbar presentaion primary lateral sclerosis umn onset. The age distribution and symptoms of spinal bulbar muscular atrophy sbma overlap with those of another motor neuron disease, amyotrophic lateral sclerosis als, so the two are sometimes confused early in the diagnostic workup. The clinical features and xlinked inheritance pattern of this disease were described by the physician william kennedy in 1968 kennedy et al. This web only file has been produced by the bmj publishing group from an. To test the efficacy and tolerability of clenbuterol in patients with spinal and bulbar muscular atrophy sbma. Spinal and bulbar muscular atrophy sbma, also known as kennedys disease, 1 is caused by progressive degeneration of the lower motor neurons and muscle. Progressive bulbar palsy genetic and rare diseases. Spinal and bulbar muscular atrophy sbma is an xlinked neuromuscular condition caused by expansions of a cag repeat in the androgen receptor ar gene.
Pilot trial of clenbuterol in spinal and bulbar muscular. Bulbar muscular atrophy affects the bulbar and facial muscles with motor neurone loss in the brainstem. Efficacy and safety of dutasteride in patients with spinal. Spinal and bulbar muscular atrophy sbma is an xlinked and adultonset neuromuscular disease caused by abnormal cag repeat expansions in the androgen receptor ar gene 1,2,3. Pdf pilot trial of clenbuterol in spinal and bulbar. Spinal muscular atrophy sma is a genetic condition that makes the muscles weaker and causes problems with movement. Sbma is caused by the expansion of a cag trinucleotide repeat encoding a. Mim 253300 is an autosomal recessive disorder caused by degeneration of alpha motor neurons in the anterior horn of the spinal cord, leading to hypotonia, muscular. Spinal and bulbar muscular atrophy sbma is a neuromuscular disease caused by a polyglutamine polyq expansion in the androgen. They show that peripheral administration of these compounds rescues disease in two mouse models, without.
Prior studies have highlighted the importance of ar nuclear localization in sbma pathogenesis. The effects of spinal bulbar muscular atrophy sbma on quality of life qol are not well understood. Biomarkers of spinal and bulbar muscle atrophy sbma. Pdf mutant androgen receptor accumulation in spinal and. Spinalbulbar muscular atrophy a type of sma thats usually called sbma, for spinalbulbar muscular atrophy, stems from a gene defect on the x chromosome. In the early 1980s, werdnig and hoffman described a disorder of progressive muscular weakness beginning in infancy that resulted in early death, though the age of death was variable. Spinal muscular atrophy cde revision history document. Clinical features of spinal and bulbar muscular atrophy. Symptoms have been reported to first begin to develop between the third to sixth decades of life. Twenty patients with a diagnosis of sbma were given oral clenbuterol 0. The characteristic muscle weakness occurs because of a progressive degeneration of the alpha motor neuron from anterior horn cells in the spinal cord.
While some smas lead to early infant death, other diseases of this group permit. Types ii and iii are the next most common and types 0 and iv are rare. Cell reports article peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy andrew p. The most common motor neuron diseases are spinal muscular atrophy sma and amyotrophic lateral sclerosis als. We discuss recent insights into this disease with two main themes. Spinal and bulbar muscular atrophy clinical features and pathogenesis clinical features sbma, or kennedys disease, is an inherited lower motor neuron disease characterised by adultonset muscle atrophy, weakness, contraction, fasciculations, and bulbar. In those few women who have the disease, the symptoms are usually mild. Spinal muscular atrophy orphanet journal of rare diseases. Early symptoms may include tremor, muscle cramps, and muscle twitching. The consensus statementdocument was drawn up by an international group of experts, the international standard of care committee for sma part of the icc for sma. Pdf bulbar problems selfreported by children and adults. Spinal muscular atrophy an overview sciencedirect topics. Spinal and bulbar muscular atrophy, or kennedys disease, is an xlinked motor neuron disease caused by polyglutamine repeat expansion in.
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