Spinal Muscular Atrophy


  • see eponyms under subtypes


A form of motor neuron disease


SMN1 gene chr. 5 (survival motor neuron gene), autosomal recessive with modifier genes,
Modifier genes: SMN2 gene number of copies,


SMA1 a.k.a. Werdnig-Hoffman disease: onset at birth or prenatally, hypotonia frog-like leg posturing, respiratory muscle paralysis
SMA2 a.k.a. intermediate: onset at 3 months, tongue fasciculation, tongue wasting, leg weakness
SMA3 a.k.a. juvenile SMA a.k.a. Kugelberg-Welander disease a.k.a. Wohlfart-Kugelberg-Welander disease: later onset, gradual progression, proximal weakness, fasciculations, wasting


Spinal cord: loss of anterior horn cells and astrocytosis, chromatolysis, neuronophagia, ballooned cells.

  • SMA1 and SMA2: rounded fibres, grouped atrophy type 1 or type 2, fascicular atrophy, grouped hypertrophy of type 1 fibres,
  • SMA 3: adult pattern of denervation atrophy


Nusinersen (trade name Spinraza) [small RCT]

Related articles:


  1. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF1, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
  2. Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L’Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.