Genetic spinal muscular atrophies (SMA) are caused by the loss of anterior horn cells in the spinal cord. The most common form of SMA is caused by deletions (rarely point mutations) of the SMN1 gene (e.g. SMA1 type Werdning-Hoffmann). In most cases of SMA, a conventional search for deletions is performed, in individual cases also a variant analysis.
Other rare forms, called “non-5q-SMA”, have mainly been identified by Next Generation Sequencing. This is a clinically very heterogeneous group of disorders, some of which are characterized by other leading symptoms (e.g., pontocerebellar hypoplasia). Essentially, they are characterized by loss of motor neurons in the spinal cord and lower brainstem, muscle weakness and atrophy. Differentiation is based on the age of manifestation, pattern of muscle involvement, anatomical location of the focus of manifestation, and inheritance pattern. Rough classification concerns a division into proximal and distal SMA (DSMA, equivalent to hereditary motor neuropathy (HMN)).
Karakaya et al. 2018 Hum Mut 39:1284 / Teoh et al. 2017 Neur Plast, Article ID 6509493/ Rudnik-Schöneborn et Zerres 2017 med genetik 29:21 / Peeters et al. 2014, Brain 137:2879