Distal spinal muscular atrophy

Neurology

Clinicals - History

Fact Explanation
Introduction to the disease It is an autosomal recessive disease which causes degeneration and loss of the anterior horn cells in the spinal cord as well as the brain stem nuclei. This ultimately results progressive muscle weakness. In distal spinal muscular atrophy, so called SMA IV the onset of disease is usually in the second or third decade of life.. Introduction to the disease
It is an autosomal recessive disease which causes degeneration and loss of the anterior horn cells in the spinal cord as well as the brain stem nuclei. This ultimately results progressive muscle weakness. In distal spinal muscular atrophy, so called SMA IV the onset of disease is usually in the second or third decade of life..
Muscle weakness It is a characteristic feature of the disease.Progressive degeneration and loss of the anterior horn cells in the spinal cord as well as the brain stem nuclei will give rise to above manifestation. Almost always the weakness is symmetric and progressive. However in distal spinal muscular atrophy the initial weakness and wasting is seen in distal muscles, followed by weakness of other muscle groups.The weakness begins in their second or third decade of life.. Muscle weakness
It is a characteristic feature of the disease.Progressive degeneration and loss of the anterior horn cells in the spinal cord as well as the brain stem nuclei will give rise to above manifestation. Almost always the weakness is symmetric and progressive. However in distal spinal muscular atrophy the initial weakness and wasting is seen in distal muscles, followed by weakness of other muscle groups.The weakness begins in their second or third decade of life..
Muscle wasting wasting is initially seen in distal muscles, then it spread in to other muscle groups.. Muscle wasting
wasting is initially seen in distal muscles, then it spread in to other muscle groups..
Gait disturbances Findings of SMA IV are similar to the findings of SMA III. Affected individuals experience gait disturbances in their second or third decades of life.. Gait disturbances
Findings of SMA IV are similar to the findings of SMA III. Affected individuals experience gait disturbances in their second or third decades of life..
Muscle pain/cramps Muscle cramps and pains are experienced by the affected patients. But it has not been adequately studied.,. Muscle pain/cramps
Muscle cramps and pains are experienced by the affected patients. But it has not been adequately studied.,.
Dysphonia Seen in certain patients due to vocal cord paralysis. Progressive bulbar paralysis causing multiple cranial nerve palsies will leads to above manifestation.. Dysphonia
Seen in certain patients due to vocal cord paralysis. Progressive bulbar paralysis causing multiple cranial nerve palsies will leads to above manifestation..
Facial diplegia Progressive bulbar paralysis causing multiple cranial nerve palsies in distal SMA causes bilateral facial weakness.,. Facial diplegia
Progressive bulbar paralysis causing multiple cranial nerve palsies in distal SMA causes bilateral facial weakness.,.
Respiratory failure Not Usually a complication of distal spinal muscular atrophy. If occurs, it will be in late adulthood.,. Respiratory failure
Not Usually a complication of distal spinal muscular atrophy. If occurs, it will be in late adulthood.,.
Joint contractures Not a common complication as other forms of SMA. Can be seen in affected patients in their adulthood.,. Joint contractures
Not a common complication as other forms of SMA. Can be seen in affected patients in their adulthood.,.
Scoliosis Recognized complication among SMA affected individuals. It is a major problem among most persons with SMA II as well as half of the patients with SMA III rather than in distal spinal muscular atrophy.. Scoliosis
Recognized complication among SMA affected individuals. It is a major problem among most persons with SMA II as well as half of the patients with SMA III rather than in distal spinal muscular atrophy..
Obesity Another complication encountered by affected individuals in their adulthood. Lack of energy requirement due to muscle weakness with preserved appetite can leads to this condition.,. Obesity
Another complication encountered by affected individuals in their adulthood. Lack of energy requirement due to muscle weakness with preserved appetite can leads to this condition.,.
Epilepsy SMA IV associated with progressive myoclonic epilepsy is an atypical finding encountered in some affected individuals.. Epilepsy
SMA IV associated with progressive myoclonic epilepsy is an atypical finding encountered in some affected individuals..
Family history of SMA Spinal muscular atrophy is inherited in an autosomal recessive manner so that having a positive family history increase the risk of developing SMA. Family history of SMA
Spinal muscular atrophy is inherited in an autosomal recessive manner so that having a positive family history increase the risk of developing SMA.

Clinicals - Examination

Fact Explanation
Postural tremor of the fingers Initial inspection finding of affected individuals.. Postural tremor of the fingers
Initial inspection finding of affected individuals..
Muscle atrophy Seen among affected individuals due to lower motor nerve involvement. Progressive degeneration and loss of the anterior horn cells in the spinal cord as well as brain stem nuclei giving rise to this manifestation.. Muscle atrophy
Seen among affected individuals due to lower motor nerve involvement. Progressive degeneration and loss of the anterior horn cells in the spinal cord as well as brain stem nuclei giving rise to this manifestation..
Muscle weakness Another classic finding of the disease due to lower motor nerve involvement. It is a symmetrical and progressive weakness. Seen in second or third decades in their life. . Muscle weakness
Another classic finding of the disease due to lower motor nerve involvement. It is a symmetrical and progressive weakness. Seen in second or third decades in their life. .
Tongue fasciculation A manifestation due to bulbar involvement. not seen in all the affected individuals.. Tongue fasciculation
A manifestation due to bulbar involvement. not seen in all the affected individuals..
Dysarthria and hoarseness. It is a recognized finding .Progressive bulbar paralysis causing palatal and vocal cord palsies, and tongue involvement may give rise to this manifestation.. Dysarthria and hoarseness.
It is a recognized finding .Progressive bulbar paralysis causing palatal and vocal cord palsies, and tongue involvement may give rise to this manifestation..
Bilateral facial weakness Cranial nerve examination finding in distal SMA. progressive bulbar paralysis causing multiple cranial nerve palsies will leads to this manifestation.. Bilateral facial weakness
Cranial nerve examination finding in distal SMA. progressive bulbar paralysis causing multiple cranial nerve palsies will leads to this manifestation..
Ophthalmoplegia Another atypical cranial nerve finding seen in some patients due to oculomotor nerve palsy.,. Ophthalmoplegia
Another atypical cranial nerve finding seen in some patients due to oculomotor nerve palsy.,.
Higher functions examination findings .They have normal higher functions. There is no memory or intellectual impairment seen in affected individuals.. Higher functions examination findings
.They have normal higher functions. There is no memory or intellectual impairment seen in affected individuals..
Sensory nerve system examination findings There is no detectable sensory impairment in affected individuals. Sensory nerve system examination findings
There is no detectable sensory impairment in affected individuals.

Investigations - Diagnosis

Fact Explanation
Full blood count Diagnosis is mainly based on history and clinical examination. Laboratory investigations are mainly focused on exclusion of other DD's and thereby supporting the diagnosis. FBC is one such essential investigation to be carried out.. Full blood count
Diagnosis is mainly based on history and clinical examination. Laboratory investigations are mainly focused on exclusion of other DD's and thereby supporting the diagnosis. FBC is one such essential investigation to be carried out..
ESR and CRP Essential investigations,should be carried in all patients with suspected SMA to exclude other inflammatory causes.. ESR and CRP
Essential investigations,should be carried in all patients with suspected SMA to exclude other inflammatory causes..
Creatine kinase level Affected individuals may have normal or increased creatine kinase level.,. Creatine kinase level
Affected individuals may have normal or increased creatine kinase level.,.
Electromyography (EMG) Denervation and diminished motor action potential amplitude is a recognized feature. An unique feature in SMA that can be identified in EMG is a regular spontaneous motor unit activity. Polyphasic waves, positive sharp waves, fibrillations as well as reduced interference pattern with maximal effort can be identified.,. Electromyography (EMG)
Denervation and diminished motor action potential amplitude is a recognized feature. An unique feature in SMA that can be identified in EMG is a regular spontaneous motor unit activity. Polyphasic waves, positive sharp waves, fibrillations as well as reduced interference pattern with maximal effort can be identified.,.
Nerve conduction velocities (NCV) Motor and sensory NCVs are usually found to be normal. Useful investigation to exclude other DD's. Nerve conduction velocities (NCV)
Motor and sensory NCVs are usually found to be normal. Useful investigation to exclude other DD's.
Muscle biopsy Group atrophy of type 1 and type 2 muscle fibers can be identified. It is also useful to exclude certain other diseases mentioned under DD.. Muscle biopsy
Group atrophy of type 1 and type 2 muscle fibers can be identified. It is also useful to exclude certain other diseases mentioned under DD..
Nerve histology In the prenatal forms of SMA there will be hypomyelination of the peripheral nerve. In other forms including distal SMA, nerves show normal histology.. Nerve histology
In the prenatal forms of SMA there will be hypomyelination of the peripheral nerve. In other forms including distal SMA, nerves show normal histology..
Molecular Genetic Testing The exact diagnosis of SMA is based on molecular genetic testing.Mutations in SMN1 gene can be identified. Presence of increased SMN2 copy numbers usualy modify the phenotype.. Molecular Genetic Testing
The exact diagnosis of SMA is based on molecular genetic testing.Mutations in SMN1 gene can be identified. Presence of increased SMN2 copy numbers usualy modify the phenotype..

Investigations - Management

Fact Explanation
Lung function test Carried out as a follow up investigation to assess FVC to assess risk of developing respiratory failure if their is any suspicion.. Lung function test
Carried out as a follow up investigation to assess FVC to assess risk of developing respiratory failure if their is any suspicion..
Random blood sugar Some affected individuals may at a risk of developing recurrent hypoglycemia. So to identify that this investigation is carried out.. Random blood sugar
Some affected individuals may at a risk of developing recurrent hypoglycemia. So to identify that this investigation is carried out..
Lung function tests Not perform in all patients but only in suspected cases of respiratory involvement. FVC can be used for the assessment of lung functions by using hand-held spirometer.Decompensation during respiratory infection is more likely if FVC is less than 40%. Lung function tests
Not perform in all patients but only in suspected cases of respiratory involvement. FVC can be used for the assessment of lung functions by using hand-held spirometer.Decompensation during respiratory infection is more likely if FVC is less than 40%.
Chest x ray Can perform suspected case of pneumonia which is a complication of encountered in SMA. Chest x ray
Can perform suspected case of pneumonia which is a complication of encountered in SMA.
Amniocentesis or chorionic villus sampling Performed in prenatal diagnosis in pregnancies.Analysis of DNA extracted from fetal cells is carried out Those DNA is extracted either by amniocentesis performed around ~15-18 weeks’ gestation or chorionic villus sampling performed around ~10-12 weeks’ gestation.. Amniocentesis or chorionic villus sampling
Performed in prenatal diagnosis in pregnancies.Analysis of DNA extracted from fetal cells is carried out Those DNA is extracted either by amniocentesis performed around ~15-18 weeks’ gestation or chorionic villus sampling performed around ~10-12 weeks’ gestation..

Management - Supportive

Fact Explanation
Proper counselling, patient and family education Once diagnosis is established proper counselling should be carried out by the doctor with the explanation of nature of the disease, life expectancy and complications. Educate them well regarding importance of proper follow up. Tell the family members that patient may not able do their day today works alone and they may need family members helping hand. Tell them that patient may need walking aids in the late stage of disease.. Proper counselling, patient and family education
Once diagnosis is established proper counselling should be carried out by the doctor with the explanation of nature of the disease, life expectancy and complications. Educate them well regarding importance of proper follow up. Tell the family members that patient may not able do their day today works alone and they may need family members helping hand. Tell them that patient may need walking aids in the late stage of disease..
Dietary measures There is no curative treatment for SMA. treatment is usually supportive. Dietary measures is need to prevent obesity in affected individuals in their adulthood.,. Dietary measures
There is no curative treatment for SMA. treatment is usually supportive. Dietary measures is need to prevent obesity in affected individuals in their adulthood.,.
Physiotherapy and occupational therapy Multidisciplinary approach is needed. Physiotherapy is carried out in order to prevent development of joint contractures and to improve functional outcomes.. Physiotherapy and occupational therapy
Multidisciplinary approach is needed. Physiotherapy is carried out in order to prevent development of joint contractures and to improve functional outcomes..
Respiratory support Not usually need in distal spinal muscular atrophy. Noninvasive respiratory support can be provided if there is a need.. Respiratory support
Not usually need in distal spinal muscular atrophy. Noninvasive respiratory support can be provided if there is a need..
Orthosis Used to support the body and to aid walking. It allows the affected individual to be upright rather than prone but it does not prevent scoliosis. Orthosis may useful in late stage of disease.. Orthosis
Used to support the body and to aid walking. It allows the affected individual to be upright rather than prone but it does not prevent scoliosis. Orthosis may useful in late stage of disease..
Pain killers Simple analgesics can be use if patient complains pain.. Pain killers
Simple analgesics can be use if patient complains pain..
Genetic Counseling It is "the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions." Since this is a autosomal recessive inherited disease genetic counselling is a must. Family members and patient should educate about the carrier detection methods as well as the family planing methods.. Genetic Counseling
It is "the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions." Since this is a autosomal recessive inherited disease genetic counselling is a must. Family members and patient should educate about the carrier detection methods as well as the family planing methods..

Management - Specific

Fact Explanation
Orthopedic surgeries for scoliosis Need in some patients. If patients who are nonambulatory, develop spinal curvatures of more than 50 degrees, they may require a surgery. In case of severe scoliosis vertical expandable prosthetic titanium rib (VEPTR) can be used.. Orthopedic surgeries for scoliosis
Need in some patients. If patients who are nonambulatory, develop spinal curvatures of more than 50 degrees, they may require a surgery. In case of severe scoliosis vertical expandable prosthetic titanium rib (VEPTR) can be used..
Valproic acid (VPA) Drug treatment for SMA is still under investigation. VPA increases SMN protein levels through transcriptional activation. But it may also increases the expression of additional serine/arginine (SR). Drug causes few neurological side effects, hematological as well as hepatic side effect. Further studies by clinical trials is needed,,. Valproic acid (VPA)
Drug treatment for SMA is still under investigation. VPA increases SMN protein levels through transcriptional activation. But it may also increases the expression of additional serine/arginine (SR). Drug causes few neurological side effects, hematological as well as hepatic side effect. Further studies by clinical trials is needed,,.
Phenylbutyrate It is a short-chain fatty acid. Studies suggest that it will stimulate SMN2 gene activity as well as increase SMN protein levels. It is less toxic and provides protection against various stimuli. However further studies is needed.,. Phenylbutyrate
It is a short-chain fatty acid. Studies suggest that it will stimulate SMN2 gene activity as well as increase SMN protein levels. It is less toxic and provides protection against various stimuli. However further studies is needed.,.
Gene therapy Still under experiment level.It is done by using viral vectors to replace SMN1.. Gene therapy
Still under experiment level.It is done by using viral vectors to replace SMN1..
Stem cell therapy It also under the experiment level. Cell replacement is performed either by activation of endogenous stem cells in the CNS or transplantation of stem cell-derived cells that have undergone maturation in vitro.. Stem cell therapy
It also under the experiment level. Cell replacement is performed either by activation of endogenous stem cells in the CNS or transplantation of stem cell-derived cells that have undergone maturation in vitro..

Concise, fact-based medical articles to refresh your knowledge

Access a wealth of content and skim through a smartly presented catalog of diseases and conditions.

  1. D'AMICO A, MERCURI E, TIZIANO FD, BERTINI E. Spinal muscular atrophy Orphanet J Rare Dis [online] :71 [viewed 30 October 2014] Available from: doi:10.1186/1750-1172-6-71
  2. LIYANAGE DS, PATHBERIYA LS, GOONERATNE IK, VITHANAGE KK, GAMAGE R. Association of type IV spinal muscular atrophy (SMA) with myoclonic epilepsy within a single family Int Arch Med [online] , 7(1):42 [viewed 30 October 2014] Available from: doi:10.1186/1755-7682-7-42
  3. MOHSENI J, ZABIDI-HUSSIN ZA, SASONGKO TH. Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy Genet Mol Biol [online] 2013 Sep, 36(3):299-307 [viewed 26 October 2014] Available from: doi:10.1590/S1415-47572013000300001
  4. PENTTILä SINI, JOKELA MANU, HACKMAN PETER, MAIJA SAUKKONEN ANNA, TOIVANEN JARI, UDD BJARNE. Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2. Eur J Hum Genet [online] December, 20(11):1193-1196 [viewed 30 October 2014] Available from: doi:10.1038/ejhg.2012.76
  5. PRIDMORE C, BARAITSER M, BRETT EM, HARDING AE. Distal spinal muscular atrophy with vocal cord paralysis. J Med Genet [online] 1992 Mar, 29(3):197-199 [viewed 26 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015897
  6. PRIOR TW, RUSSMAN BS, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Spinal Muscular Atrophy [online] 1993 [viewed 26 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301526
  7. YAMADA M, KANO M, CHIDA K, FURUKAWA T, TSUKAGOSHI H. Asymptomatic benign familial spinal muscular atrophy with hypertrophy of the calves and high creatine kinase levels. J Neurol Neurosurg Psychiatry [online] 1988 Mar, 51(3):452-453 [viewed 26 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1032885