Handbook of Genetic Counseling/Spinal Muscular Atrophy (SMA1)

Spinal Muscular Atrophy (SMA1)

SMA is the number one genetic killer of children under the age of 2


  • Establish rapport with small talk and introduce myself
  • Assess the concerns of the family and what they hope to learn today
  • Ascertain the level of understanding of SMA
  • Briefly discuss the topics to be discussed during the appointment
  • Ask if anyone has any questions

Elicit Family History and Pedigree



  • Spinal muscular atrophy (SMA) is a group of inherited neuromuscular diseases that attack motor neurons, which control the movement of voluntary muscles. This disease causes anterior horn cells (lower motor neurons) in the base of the brain and spinal cord to gradually disintegrate.

Types of SMA

  • Prior to the availability of molecular diagnosis, SMA was classified into subgroups. These subgroup classifications are useful for prognosis and management.
  • Infantile progressive spinal muscular atrophy (SMA 1)
  • Intermediate SMA (SMA 2)
  • Juvenile SMA (SMA 3)
  • Adult SMA (SMA 4)
  • These forms differ in the age of onset, the severity, the progression rate, and in the adult form, the muscles affected.


  • Mode of inheritance:
    • SMA is an autosomal recessive disorder
  • Chromosome location:
    • Chromosomal locus 5q11-q13
  • Molecular Genetics:
    • SMN (survival motor neuron) has been identified as the primary SMA-determining gene
      • The SMN gene is very complex, containing repetitive sequences, pseudogenes, deletions and inverted duplications
      • 2 copies exist: the telomeric copy (SMNT ) and the centromeric copy (SMNC)
      • These only differ by a few nucleotides
      • Unaffected individuals have 2 copies arranged in tandem on each chromosome 5 (centromeric and telomeric)
    • A defect in both copies of the SMNT gene causes SMA
    • Individuals with SMA are either:
      • Homozygous for a deletion of exon 7 of the SMNT gene (95% of cases) or
      • Compound heterozygotes for a deletion of exon 7 of the SMNT gene and a subtle intragenic mutation of SMN T (5% of cases)
    • Abnormal protein product is produced by mutant SMN T
      • Normal gene products are thought to play a role in splicing; it has been shown to be necessary for pre-mRNA splicing


  • One study suggests that SMA occurs at a frequency of ~4: 100,000
  • 1:40-1:80 are carriers for SMA

Clinical Features (general for all types of SMA)

  • Progressive degeneration and loss of the lower motor neurons (anterior horn cells) in the spinal cord and sometimes in the brainstem nuclei.
    • Results in muscle weakness and atrophy
    • The onset varies from before birth until adulthood
    • The weakness is symmetric and progressive
  • Contractures, usually mild
  • Anterior horn cell involvement, apparent due to tongue fasciculations and absent deep tendon reflexes
  • Respiratory failure
  • Variable cranial nerve involvement: opthalmoplegia, facial diplegia

Additional Specific SMA1Clinical Features

  • Lack of motor development
  • Infants with the gravest prognosis have sucking and swallowing difficulty
  • Face muscles are completely spared
  • Ocular and diaphragmatic muscles are involved late in the disease
  • The heart is normal
  • Intellect is normal
  • Prognosis depends primarily upon respiratory function

Risk Assessment

  • ~98% of parents of an affected child are carriers, and ~2% are not carriers, thus the mutation was de novo
  • The risk of occurrence/recurrence for parents who are both carriers is 25%, while the risk of having an unaffected carrier child is 50%.

Age of Onset, natural history and life span

  • The age of onset for SMA1 is before 6 months
  • The lifespan is two years or less


  • Diagnostic: A direct DNA analysis to detect a homozygous deletion of exon 7 of SMNT is used to confirm a clinical diagnosis.
    • This test has one limitation, it does not detect intragenic mutations
    • If only one deletion SMNT is present, this does not confirm a clinical diagnosis but supports a clinical diagnosis.
  • Carrier: Dosage testing for carrier detection. This PCR test determines the # of exon 7 containing SMNT gene copies that are present in an individual.
    • Both technical and interpretation limitations for this test
      • Some carriers have 2 SMNT gene copies on one chromosome
      • Some carriers have one normal allele and a subtle mutation
      • de novo mutations occur in 2% of SMA patients, meaning that only one parent is a carrier
  • Prenatal: this test is possible for fetuses at a 25% risk when the disease causing SMN mutations in both parents is known
    • Analysis of fetal DNA obtained via CVS or amnio
  • If the SMNT gene is normal, two other tests are available:
    • Neurophysiologic studies-electromyography (EMG). This reveals devervation and diminished motor potential amplitude.
    • Muscle biopsy- reveals evidence of devervation with no other structural abnormalities.


  • Physical therapy and occupational therapy to promote and maintain motor skills
  • Monitoring of respiratory function, ventilatory support (usually not used for SMA1 patients)
  • SMA1 patients that aren't sucking or swallowing well may need a gastrostomy (g-tube)

Differential Diagnosis

  • SMA1 is considered in the differential diagnosis of the "floppy child
  • Prader-Willi syndrome
  • Pompe's disease (when cardiomegaly is present)
  • Congenital myotonic dystrophy
  • Congenital muscular dystrophy

Psychosocial Issues

  • The parents,grandparents and immediate family have an impending death (patients with SMA1) and are typically having a difficult time dealing with the severity of the disease.
  • Counselors should encourage parents to discuss their feelings and concerns.
  • As this disease is very draining on the parents,grandparents and immediate family, the counselor should check on the support network available to the family.


  • Facts about Spinal Muscular Atrophy. Muscular Dystrophy Association

Web References




The information in this outline was last updated in 2002.