Predominantly Proximal Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is a term used to describe a varied group of inherited disorders characterized by weakness and muscle wasting, secondary to degeneration of both anterior horn cells of the spinal cord and brainstem motor nuclei without pyramidal tract involvement.
Three subtypes of autosomal-recessive predominantly proximal SMA have been described, all linked to chromosome 5q. A common nomenclature subdivides SMA into types I, II, and III, based on age of onset and age of death, whereas the other approach classifies cases as severe, intermediate, and mild, based on ability to achieve independent sitting, independent standing, and walking. The International Consortium on SMA attempted to standardize the classification of childhood SMA to provide a rational basis for linkage studies and therapeutic trials (Table 12.4) (97).SMA type I (Werdnig-Hoffman, severe form) was defined by the International Consortium on SMA as follows: onset from birth to 6 months, no achievement of sitting without support, and death usually prior to age 2 years. In SMA type II (intermediate form), onset is before 18 months, sitting is usually obtained, but standing and ambulation are never obtained and death
12.4
Childhood Onset Proximal Spinal Muscular Atrophy (SMA)
| SMA I (WERNIG HOFFMAN) | SMA II (INTERMEDIATE SMA) | SMA III (KUGELBERG WELANDER) | |
| Onset | 8 months IIIa 3 years | ||
| Genetics | SMN1: AR homozygous SMN2: 2 SMN2 genes. It appears that a higher number of SMN2 copies in the setting of SMN1 mutations is associated with a less severe clinical SMA phenotype: SMA I (severe): two or three gene copies of SMN2; SMA II: three copies of SMN2; SMA III: four to eight copies of SMN2. However, substantial variations in SMA phenotype and disease severity can exist with a given SMN2 copy number, so it is not recommended that disease severity be predicted based soley on SMN2 copy numbers. Although we now know that SMN protein is expressed widely in many tissues throughout the body, its function is still not completely understood at this time (112).
More medical literature on Medic.Studio
More on the topic Predominantly Proximal Spinal Muscular Atrophy:
-
Infectious diseases -
Internal diseases -
Obstetrics and Gynaecology -
Pediatrics -
Veterinary medicine -
-
Conflictology -
Ecology -
Economy -
Finance -
History -
Law -
Medicine -
Philosophy -
Religious studies -
|