Genetic abnormalities involved in SMALED2 better understood

Spinal muscular atrophy, lower extremity-predominant type 2, or SMALED2 is a rare form of proximal spinal muscular atrophy. It usually progresses more slowly than SMA. 

Two forms can be found: SMALED 2A, the classic form of the disease, begins in childhood and evolves very slowly, and SMALED 2B, more severe, whose first manifestations appear in utero. Both are linked to the BICD2 gene involved in the transport of newly synthesized proteins and lipids.

Two articles published in February 2020 improve knowledge of anomalies in the BICD2 gene in order to guide the interpretation of the variants identified on this gene.

  • The American team of Daniel Koboldt has listed the 21 anomalies of the BICD2 gene already identified in 99 patients with SMALED2. They have shown life-threatening  de novo mutations are associated with the presence of more severe symptoms and progression (extreme amyotrophy, brain abnormalities, convulsions, etc.).
  • A spanish article presents 3 new anomalies of the BICD2 gene and describes a characteristic muscle damage observed on MRI. A patient has signs of sensitivity sensitivity, which requires confirmation and clarification on a larger number of patients.
  • In the 2 studies, the forms observed confirm the involvement of the lower limbs with deformation of the foot.


The genotypic and phenotypic spectrum of BICD2 variants in spinal muscular atrophy. Koboldt DC, Waldrop MA, Wilson RK, Flanigan KM. Ann Neurol. 2020 Apr;87(4):487-496.


The clinical spectrum of BICD2 mutations. Frasquet M, Camacho A, Vílchez R, Argente-Escrig H, Millet E, Vázquez-Costa JF, Silla R, Sánchez-Monteagudo A, Vílchez JJ, Espinós C, Lupo V, Sevilla T. Eur J Neurol. 2020 Feb 13.