Authors

A.J. van der Kooi, M.D., Ph.D.
M. de Visser, M.D., Ph.D., Professor of Neuromuscular Diseases

Clinical features
Autosomal recessive LGMD The clinical picture of autosomal recessive LGMD closely resembles that of Duchenne/Becker type of muscular dystrophy (DMD/BMD). There is a variable age of onset although in most families the first symptoms occur in the first or second decade. Weakness of the limb-girdle muscles is first manifesting in the pelvic girdle, and is progressive. Involvement of the shoulder girdle muscles occurs about 2-10 years later. Some forms have a course similar to DMD, in which the ability to walk is lost around the age of 10 years. Other forms have a less rapid course, sometimes even without losing ambulance. Calf enlargement is frequently seen, especially in sarcoglycanopathies. Read more

Epidemiology
In 1991, a world survey of population frequencies of inherited neuromuscular diseases was undertaken by Emery. The prevalence and incidence rates for mainly adult onset cases of limb girdle muscular dystrophy lie between 20-40 x 10 -6 . Autosomal recessive (Duchenne-like) muscular dystrophy of childhood appeared to be a rare disorder with a prevalence of less than 5 x 10 -6 . It is, however, commoner in certain Arabic communities in North Africa, in Switzerland, in certain inbred communities in North America originating from Switzerland, and in Brazil. It has been estimated that around 3-12% of isolated males diagnosed as having X-linked Duchenne muscular dystrophy may in fact have this clinically similar autosomal recessive disorder. Read more

Differential diagnosis
It remains very important to exclude all other possible causes of a limb girdle syndrome. In a detailed survey it became evident that 25% percent of patients had been misdiagnosed. Duchenne and Becker dystrophy and manifesting carriers of these X-linked dystrophies usually present with a limb girdle syndrome. These disorders are identified by dystrophin analysis in the skeletal muscle and DNA-Xp21 screening, which gives an accurate diagnosis in 90% of the cases. The karyogram should always be checked in female persons in order to rule out Turner syndrome, structurally abnormal X-chromosomes or X-autosome translocations. Read more

Ancillary investigations
Serum CK activity can be markedly elevated (up to 188 times the normal value), especially in the severe Duchenne-like forms. CK can be markedly raised in preclinical stages and it shows a tendency to decrease with the duration of the disease. In the dominant forms serum CK activity is usually only mildly elevated. Electromyography demonstrates a myopathic pattern in most cases of LGMD, consisting of small amplitude, short duration motor unit action potentials (MUAPs) and an increased percentage of polyphasic potentials. Read more

Genetics

Genes involved in limb girdle muscular dystrophy:
DYSF - Dysferlin
SGCA - Sarcoglycan-alpha
SGCB - Sarcoglycan-beta
SGCG - Sarcoglycan-gamma
SGCD - Sarcoglycan-delta
CAV3 - Caveolin
CAPN3 - Calpain 3
FKRP - Fukutin-Related protein
LMNA - Laminin A/C
TTID - Titin immunoglobulin domain protein
TCAP - Telethonin
TRIM32 - Tripartite motif-containing protein 32

Therapy
No specific therapy is known. Patients should be counseled about the inheritance pattern and the course of this disorder. Many patients receive physical therapy to prevent worsening of contractures although its efficacy has not been evaluated. In the majority of patients, progressive weakness leads to disability necessitating additional aids and adjustments, like a cane, home alterations, and wheelchair. In this stage of the disease referral to a rehabilitation physician should be considered. Read more

References
Bushby KMD. The limb-girdle muscular dystrophies. In Emery AEH, ed. Diagnostic criteria for neuromuscular disorders , pp 17-22. London: Royal Society of Medicine Press, 1997. van der Kooi AJ, Barth PG, Busch HF, de Haan R, Ginjaar HB, van Essen AJ et al . Read more