The different types of spinal muscular atrophy may present differently but clinical symptomatology may be similar to some extent.

The following system-wise presentation is commonly in seen in SMAs:

General Appearance: Infant patients may initially present to be weak, floppy and flaccid.

Integumentary system: SMA type 1 babies may appear cyanotic upon birth.

Head and Neck: Sucking and swallowing ability is impaired.

Chest and heart: Respiratory difficulty may be presented with a hypotonic diaphragm muscle.

Abdomen: Hypotonic abdominal muscles may be observed in supple babies.

Extremities: Occasional tremors of fingers and muscular fasciculation may be observed in chronic infantile forms of SMA. Pseudohyperthrophy of gastrocnemius muscle (calf muscle) may be seen in SMA II.

Neurologic: Developmental and motor function delay are evident in SMA type 2. Late stage SMA may present with poor deep tendon reflexes.

• Weakness

  They have extremely weak muscle tone (hypotonia) at birth. Their respiratory muscles are very weak and they often do not survive past infancy due to respiratory failure. [ghr.nlm.nih.gov]

  Distal muscle weakness. Sensory and autonomic nervous systems may also be involved. Bulbo-SMA, or Kennedy's syndrome Age of onset : 20-40 years. Features : bulbar and lower motor neurone weakness. Muscle cramps, facial fasciculations, hand tremor. [patient.info]

  They may also experience mild muscle weakness and are at greater risk for respiratory infections. Most patients with Type 3 SMA have a life expectancy close to normal. [my.clevelandclinic.org]

  Disease presents with muscular weakness in lower more than upper extremities. Progressive respiratory insufficiency may happen due to weakness of respiratory muscles. Kennedy's disease is also considered a form of SMA. [aanem.org]

• Difficulty Walking

  While children with type III usually are able to walk, most have some difficulty walking. Some may eventually need to use a wheelchair. Symptoms usually appear around 18 months of age or in early childhood. [childrenshospital.org]

  Children can sit without support but are unable to stand or walk unaided. Children also may have respiratory difficulties. [ninds.nih.gov]

  These children show signs of clumsiness, difficulty walking, mild muscle weakness, and may be developmentally delayed. These children live long into their adult years. [chw.org]

• Developmental Delay

  Developmental delays can be early signs of a serious medical condition. Always trust your instincts. If something about your child’s development doesn’t feel quite right, don’t delay. Early diagnosis is key… it’s a SMArt Move. [curesma.org]

  These children show signs of clumsiness, difficulty walking, mild muscle weakness, and may be developmentally delayed. These children live long into their adult years. [chw.org]

  These symptoms include: Developmental delays Inability to support the head Inability to sit up without assistance Breathing and swallowing difficulties which may lead to choking Spinal muscular atrophy Type 2 is less severe than type I and begins to develop [cedars-sinai.edu]

  Children affected by spinal muscular atrophy (SMA) often have developmental delays. [babysfirsttest.org]

• Swelling

  These symptoms arise from the growth of the lesion as well as from swelling around the lesion. How long have I had it? Unfortunately, there is no accurate means to determine how long a patient has had spinal metastases. [urmc.rochester.edu]

  Extra fluid in the head can cause it to swell and put pressure on the brain. In some cases, a surgeon needs to drain the extra fluid from a baby’s brain. [marchofdimes.org]

  It can also cause anaphylaxis, a potentially life-threatening condition in which swelling of the face and airways can make breathing difficult. [mayoclinic.org]

  The extra fluid can cause the spaces in the brain, called ventricles, to become too large and the head can swell. Hydrocephalus needs to be followed closely and treated properly to prevent brain injury. [cdc.gov]

  A meningocele, a cystic swelling of the dura and arachnoid, protrudes through the spina bifida defect in the vertebral arch. A person with a meningocele may have no neurologic sequelae. [emedicine.medscape.com]

• Unable to Stand

  Children can sit without support but are unable to stand or walk unaided. Children also may have respiratory difficulties. [ninds.nih.gov]

  Bone strength decreases as patients become unable to stand, and they are at risk for bone fractures (breaks). Also, scoliosis (spinal curvature) nearly always develops as these children grow. Life span may extend beyond the school years. [nationwidechildrens.org]

• Respiratory Distress

  KEYWORDS: Distal neuropathy; IGHMBP2; Respiratory distress; SMARD1; Spinal muscular atrophy with respiratory distress [ncbi.nlm.nih.gov]

  SMA with respiratory distress type 1(SMARD1) Age of onset : 1-6 months. Features : similar to SMA types I-IV but the predominant symptom is severe respiratory distress due to involvement of the diaphragm muscles. [patient.info]

  "Respiratory failure in infants due to spinal muscular atrophy with respiratory distress type 1". Intensive Care Medicine. 32 (11): 1851–1855. doi:10.1007/s00134-006-0346-8. PMID 16964485. [en.wikipedia.org]

• Dyspnea

  Hyporeflexia may have other causes, including hypothyroidism, electrolyte imbalance (e.g. excess magnesium), drug induced (e.g. the symptoms of benzodiazepine intoxication include confusion, slurred speech, ataxia, drowsiness, dyspnea, and hyporeflexia [en.wikipedia.org]

• Constipation

  Constipation and gastroesophageal reflux are frequent. Etiology Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. [orpha.net]

  The most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. [fda.gov]

  Therefore, constipation, poor nutrition, and drooling are common. Respiratory muscle weakness frequently leads to pneumonia, which can be life threatening. [nationwidechildrens.org]

  Constipation is a common problem as is being able to control excessive drooling (secretions), and getting proper nutrition and calories for proper weight gain. [smasupport.com]

  However, this drug (nusinersen) is associated with several risks and adverse effects, which include respiratory conditions, increased risks of infections and constipations. [evolving-science.com]

• Dysphagia

  Dysphagia. 2010 Sep;25(3):261-4. doi: 10.1007/s00455-009-9269-1. Epub 2010 Jan 20. Author information 1 Department of Occupational Therapy, Gangnam Severance Hospital, Yonsei University, Gangnam-gu, Seoul, 135-720, Republic of Korea. [ncbi.nlm.nih.gov]

  Patients with SMA also have significant difficulty with physical activities such as walking, crawling, and I coordination, neck and had control and dysphagia ( trouble swallowing ). [stemcellthailand.org]

  Dysphagia may be present. Most children are confined to a wheelchair by age 2 to 3 years. The disorder is often fatal in early life, frequently resulting from respiratory complications. [merckmanuals.com]

• Dysphagia

  Dysphagia. 2010 Sep;25(3):261-4. doi: 10.1007/s00455-009-9269-1. Epub 2010 Jan 20. Author information 1 Department of Occupational Therapy, Gangnam Severance Hospital, Yonsei University, Gangnam-gu, Seoul, 135-720, Republic of Korea. [ncbi.nlm.nih.gov]

  Patients with SMA also have significant difficulty with physical activities such as walking, crawling, and I coordination, neck and had control and dysphagia ( trouble swallowing ). [stemcellthailand.org]

  Dysphagia may be present. Most children are confined to a wheelchair by age 2 to 3 years. The disorder is often fatal in early life, frequently resulting from respiratory complications. [merckmanuals.com]

• Failure to Thrive

  Disease progression is clinically associated with failure to thrive or weight loss, mainly caused by chewing and swallowing difficulties. [ncbi.nlm.nih.gov]

  Failure to thrive. If your child has SMA, you might look for symptoms such as: Delays in gross motor development, such as walking—or the loss of skills already mastered. Frequent respiratory infections that get worse with each infection. [gillettechildrens.org]

  While intellectual development remains normal, muscle weakness often leads to respiratory failure and generalized failure to thrive. There are three types of SMA, each with varying degrees of severity and limited treatment options. [globalgenes.org]

  Individuals with such difficulties can be at increase risk of over or undernutrition, failure to thrive and aspiration. [en.wikipedia.org]

• Delayed Gastric Emptying

  Specialty Collaborations & Other Services Gastro-Intestinal & Bowel Function Gastrointestinal problems such as reflux, delayed gastric emptying, and constipation are common. [medicalhomeportal.org]

• Tongue Atrophy

  Other features include poor head control, a bell-shaped chest, weak cry and cough, tongue atrophy and fasciculation, and paradoxical breathing. Type II SMA presents later in the first year of life or up to about 2 years of age. [medicalhomeportal.org]

• Fasciculation of the Tongue

  The child presented at two months of life with intense muscle weakness affecting predominantly proximal portions of the limbs, especially the legs, muscle hypotonia, fasciculation of the tongue, and severe respiratory muscle involvement. [ncbi.nlm.nih.gov]

• Muscular Atrophy

  Other forms of spinal muscular atrophy and related motor neuron diseases, such as spinal muscular atrophy with progressive myoclonic epilepsy, spinal muscular atrophy with lower extremity predominance, X-linked infantile spinal muscular atrophy, and spinal [ghr.nlm.nih.gov]

  Spinal Muscular Atrophy (SMA) Menu What is spinal muscular atrophy (SMA)? Spinal muscular atrophy (SMA) is a group of genetic diseases that cause weakness and wasting in the voluntary muscles of infants and children and, more rarely, in adults. [my.clevelandclinic.org]

  […] the disease; and, WHEREAS, Spinal Muscular Atrophy can strike anyone of any age, race or gender; and, WHEREAS, increased awareness of Spinal Muscular Atrophy will lead to increased knowledge and increased support for both disease research and the families [michigan.gov]

• Muscle Weakness

  The weakness tends to be more severe in the muscles that are close to the center of the body (proximal) compared to muscles away from the body's center (distal). The muscle weakness usually worsens with age. [ghr.nlm.nih.gov]

  Limp or floppy muscles. Poor head control. Lack of movement. Muscle weakness that grows worse. Failure to thrive. [gillettechildrens.org]

  General clinical signs are that of lower motor neurone weakness: Flaccid weakness (muscles soft and floppy) Hypotonia Reduced or absent tendon reflexes Normal or absent plantar reflexes Muscle fasciculation Muscle atrophy SMA type I Age of onset : Features [patient.info]

  They may also experience mild muscle weakness and are at greater risk for respiratory infections. Most patients with Type 3 SMA have a life expectancy close to normal. [my.clevelandclinic.org]

• Fracture

  In the first days of the patient's life, fractures of the right femur and right humerus were found; however, calcium-phosphate metabolism and densitometric examination were normal. [ncbi.nlm.nih.gov]

  Devices Market Size, Share & Industry Analysis, By Product Type (Cervical Devices, Thoracolumbar Devices, Interbody Devices, and Biologics), By Disease Indication (Degenerative Disc Disease, Complex Deformity, Traumas & Fractures, and Others), By End [globenewswire.com]

  A plain film showing an osteoporotic fracture strongly decreased the risk of SEM. [jamanetwork.com]

• Proximal Muscle Weakness

  The clinical symptoms of SMA are progressive proximal muscle weakness and paralysis. Here we describe a 20-year-old Turkmenistan male with SMA who presented with uncommon pathological reflexes and asymmetric onset of weakness. [ncbi.nlm.nih.gov]

• Myopathy

  Owing to the similar clinical features of SMA and congenital myopathy, an electrodiagnostic study and muscle biopsy could create confusion in the correct diagnosis in some cases. [ncbi.nlm.nih.gov]

  Differential diagnosis Differential diagnoses include SMA2, congenital muscular dystrophies, congenital myopathies, some early-onset mitochondrial disorders, and carbohydrate metabolism disorders (see these terms). [orpha.net]

  […] electrolyte imbalance (e.g. excess magnesium), drug induced (e.g. the symptoms of benzodiazepine intoxication include confusion, slurred speech, ataxia, drowsiness, dyspnea, and hyporeflexia).[2] Diseases associated with hyporeflexia include: Centronuclear myopathy [en.wikipedia.org]

  Differential diagnosis Motor neurone disease Primary lateral sclerosis Muscular dystrophy Congenital myopathies Disorders of carbohydrate metabolism ( glycogen storage diseases ) Myasthenia gravis Poliomyelitis Investigations Blood tests Creatine kinase [patient.info]

• Reduced Fetal Movement

  We present a male patient with SMAX2 who presented with typical symptoms at birth, preceded by reduced fetal movements in the second and third trimesters of pregnancy. [ncbi.nlm.nih.gov]

  There may be a history of reduced fetal movements in utero. Mortality/morbidity : median survival is 7 months - 95% die before 18 months. SMA type II Age of onset : 6-18 months. Features : developmental motor delay (delay in sitting, standing). [patient.info]

• Tremor

  They often have involuntary trembling (tremors) in their fingers, a spine that curves side-to-side (scoliosis), and respiratory muscle weakness that can be life-threatening. [ghr.nlm.nih.gov]

  She presented with progressive muscle weakness, tremor, seizure, and cognitive impairment. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epilepsy. [ncbi.nlm.nih.gov]

  Muscle cramps, facial fasciculations, hand tremor. Associated with type 2 diabetes and infertility. [patient.info]

  Fine tremors of the face are present in over 90% of patients. Type 2 diabetes mellitus, hand tremor, and infertility can also occur. [encyclopedia.com]

• Hand Tremor

  Tongue movements and hand tremors may be seen, but are less apparent than in Type I SMA. Contractures (tightening) of joints and scoliosis are common. [moveforwardpt.com]

  Muscle cramps, facial fasciculations, hand tremor. Associated with type 2 diabetes and infertility. [patient.info]

  They have delayed motor (physical) milestones, poor weight gain, weak cough, hand tremors, contractures (fixed deformities of joints) and scoliosis (curved spine). [rch.org.au]

  Fine tremors of the face are present in over 90% of patients. Type 2 diabetes mellitus, hand tremor, and infertility can also occur. [encyclopedia.com]

• Areflexia

  Infantile X-linked spinal muscular atrophy (SMAX2) is a rare form of spinal muscular atrophy manifesting as severe hypotonia, areflexia, arthrogryposis, facial weakness and cryptorchidism, and frequently accompanied by bone fractures. [ncbi.nlm.nih.gov]

  Therefore, damage to lower motor neurons will subsequently result in hyporeflexia and/or areflexia.[1] Note that, in spinal shock, which is commonly seen in the transection of the spinal cord (Spinal cord injury), areflexia can transiently occur below [en.wikipedia.org]

  Other symptoms include: Muscle atrophy Muscle weakness Areflexia Trouble Breathing Thin muscle mass Trouble eating or swallowing Lack of head and neck control Involuntary facial twitching Atrophic muscle changes Muscle twitching Sensory neuropathies Difficulty [stemcellthailand.org]

  Affected neonates have facial diplegia, areflexia, cardiac defects, and sometimes arthrogryposis. Death due to respiratory failure occurs within the first 6 months. [merckmanuals.com]

• Unable to Walk

  While the father first walked at the age of 19 months, the son was unable to walk at age 3 years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. [ncbi.nlm.nih.gov]

  Affected children can typically maintain a seated position without support but are unable to walk. SMA type III is often diagnosed between 18 months and three years of age. [babysfirsttest.org]

  Some people may even be paralyzed or unable to walk or move parts of their body. Even so, with the right care, most people affected by spina bifida lead full, productive lives. Learn about living with spina bifida at different ages » [cdc.gov]

  A gait disturbance was observed during the neurological examination in 18 patients (11%); of these, 14 (8%) could walk with assistance and 4 (2%) were unable to walk, 1 because of severe pain. [jamanetwork.com]

  The impairment may be so severe that the affected individual is unable to walk and may have bladder and bowel dysfunction. top What causes spina bifida? The exact cause of spina bifida remains a mystery. [ninds.nih.gov]

• Limb Weakness

  As the disease progresses patients may notice limb weakness starting in the pelvis or shoulders, or weakness of the facial and tongue muscles. Symptoms of SMA-LED often develop in infancy or early childhood. [cedars-sinai.edu]

  There is a clinical variant of SMA, known as autosomal-dominant spinal muscular atrophy characterized by a predominantly lower limb weakness and muscle wasting. [symptoma.com]

  In addition to muscle weakness, clinical features include head lag, poor sucking and swallowing, weak cry, proximal limb weakness, and lack of reflexes. Affected children never raise their head, roll over, or walk. [encyclopedia.com]

  Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. [dict.cnki.net]

The following workup and testing methods are implored in cases of spinal muscular atrophy:

Genetic Testing 

A genetic panel for SMN 1 sequencing and coding is amply suggested in cases of infantile SMA suspects [8]. Amniocentesis of the fetal chorionic villi has a sensitivity rating of 88% to 99% in the prenatal diagnosis of SMA. Recent studies reveal that carrier detection rating for SMA may rise to 90% [9].

Laboratory Testing 

The laboratory determination of creatine kinase (CK) level may be a helpful tool in a comprehensive SMA work up. Type 1 SMA will arbitrarily present with a normal CK level while the other forms may show CK elevations.

Electrodiagnostic Testing 

The use of an electromyography (EMG) and nerve conduction studies may be helpful in the diagnosis of SMA. Muscles which are not clinically affected will show signs of denervation with EMG while nerve conduction remains normal.

• Excessive Drooling

  Constipation is a common problem as is being able to control excessive drooling (secretions), and getting proper nutrition and calories for proper weight gain. [smasupport.com]

There is no available cure for SMA to date. However, there are supportive treatment options to allay the discomforts that inherently affect the SMA patients:

• Physical therapy exercises may help delay progression of SMA leading to muscular atrophy.
• Appliance or Equipment: This are mechanical aids like splints, bracing and spinal orthoses to help SMA patients to go about their daily chores [10].
• Surgical correction of exaggerated scoliosis.
• Gastrostomy placement on infants with SMA type 1.

The relative morbidity and mortality rates of SMA varies inversely with age of onset. The SMA type 1 in Werdnig-Hoffman disease carries the worst prognosis with a very high mortality rate. Life expectancy of the patient is usually unaffected with the milder forms of SMA (type 3 and type 4).

Some genetic studies point to prognosticate prenatal occurrence of SMA via amniocentesis. The findings of severe SMA by genetic studies may give some mothers the option for therapeutic abortion in some liberal countries.

Complications

The following clinical disorders are the established complications associated with spinal muscular atrophy:

• Difficulty in feeding: This is due to the inability of the infants to suck and swallow in infantile cases of SMA.
• Recurrent respiratory infections: Tongue fasciculation and ineffective swallowing may predispose patients to frequently aspirate their food.
• Flaccid paralysis
• Scoliosis
• Bed sores: Long term paraplegia may lead to pressure sores
• Respiratory failure
• Death

Spinal muscular atrophy is transmitted via an autosomal-recessive gene from both parents, meaning the mother and the father will not convey any symptoms of the disease. The offspring will carry the SMA gene defect through a homozygous deletion type of inheritance.

The inherited genetic defects on chromosome 5q11.2-13.3 are generally associated with spinal muscular atrophy type 1 to 3 [1]. Defects in genetic SMA are not exclusive to peripheral nerves but it involves the central nervous system (CNS) as well. There is a clinical variant of SMA, known as autosomal-dominant spinal muscular atrophy characterized by a predominantly lower limb weakness and muscle wasting [2].

In the United States, SMA represent the next most common autosomal-recessive genetic disorder following cystic fibrosis. The acute form of SMA in infants occurs in 1 out of 10,000 live births, while the chronic SMAs becomes evident in 1 out of 24,000 births. The chronic infantile type of SMA accounts to 50% of all cases [3].

Spinal muscular atrophy expresses in 1 out of 10,000 live births worldwide [4]. The mortality rate of acute infantile SMA (type 1) reaches 95% with a 7 month mean survival average.

The leading cause of mortality is the complication of severe respiratory infections in SMA. There is a predilection of SMA among males especially in both infantile onset types [5].

The familial spinal muscular atrophy is represented by two survival motor neurons (SMN1 and SMN2) [6]. In more than 95% of SMA cases there has been an evident homozygous gene disruption in SMN1 on the small arm loci of chromosome 5q.

These pathologic phenomenon is grossly brought about by spontaneous mutation and gene deletion. The missing SMN1 in the genetic defect will allow SMN2 to generate the missing protein for the spinal cord development although it can only come up with 10% of the actual protein chain length [7].

Genetic counselling for carrier parents may avert the emergence of an affected sibling. The prenatal amniocentesis of the fetal chorionic villus may help attending physicians prepare for any untoward eventualities during the baby’s delivery. Prompt diagnosis and early intervention is the key in reducing morbidity and mortality.

Spinal muscular atrophy or SMA is a hereditary disease characterized by progressive musclar weakness due to deterioration of the lower motor neuron (anterior horn) cells of the spinal cord including the motor nuclei of the central nervous system (brainstem).

The pathology is mainly on the motor neurons connecting the spinal cord and the brain to the muscles of the body. The more common types of spinal muscular atrophy include: Werdnig-Hoffman disease or SMA type 1 (infantile type of acute onset), SMA type 2 (chronic infantile type), Kugelberg-Welander disease or SMA type 3 (chronic juvenile onset), and the SMA type 4 (adult onset).

Definition

Spinal muscular atrophy or SMA is a hereditary disease characterized by the progressive musclar weakness due to the deterioration of the lower motor neuron (anterior horn) cells of the spinal cord including the motor nuclei of the central nervous system (brainstem).

Cause

It is due to autosomal-recessive genetic inheritance. 

Symptoms

Sucking and swallowing ability, tremors, weak abdominal muscles and respiratory difficulty are the usual symptoms

Diagnosis

Patients diagnosed with spinal muscular atrophy should be submitted to rigorous pediatric neurology follow-ups for the early classification of the disease.

Treatment and follow up

The third and fourth type of SMA may be compatible to normal living till adulthood. Offspring from patients who make it to adulthood may carry the recessive gene and should be subjected to parental genetic counselling in the future.

1. Burlet P, Burglen L, Clermont O, et al. Large scale deletions of the 5q13 region are specific to Werdnig- Hoffmann disease. J Med Genet. Apr 1996;33(4):281-3
2. Oates EC, Reddel S, Rodriguez ML, Gandolfo LC, Bahlo M, Hawke SH, Lamandé SR, Clarke NF, North KN. Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells. Brain. 2012; 135(Pt 6):1714-23 (ISSN: 1460-2156)
3. Harding AE. Inherited neuronal atrophy and degeneration predominantly of lower motor neurons. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 3rd ed. Philadelphia: WB Saunders; 1993:1051-64
4. Pearn J. Classification of spinal muscular atrophies. Lancet. Apr 26 1980; 1(8174):919-22.
5. Hausmanowa-Petrusewicz I, Zaremba J, Borkowska J, Szirkowiec W. Chronic proximal spinal muscular atrophy of childhood and adolescence: sex influence. J Med Genet. Dec 1984; 21(6):447-50.
6. Martínez-Hernández R, Bernal S, Also-Rallo E, Alías L, Barceló MJ, Hereu M, Esquerda JE, Tizzano EF. Synaptic defects in type I spinal muscular atrophy in human development.J Pathol. 2013; 229(1):49-61 (ISSN: 1096-9896)
7. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. Jun 21 2008; 371(9630):2120-33.
8. Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. May 2012; 11(5):443-52.
9. Ben-Shachar S, Orr-Urtreger A, Bardugo E, Shomrat R, Yaron Y. Large-scale population screening for spinal muscular atrophy: clinical implications.Genet Med. 2011; 13(2):110-4 (ISSN: 1530-0366)
10. Armon C. ALS 1996 and Beyond: New Hopes and Challenges. A manual for patients, families and friends. 3rd ed. Loma Linda, Calif: 2000:18.