Duchenne Muscular Dystrophy Carriers

05 November 2004

Absolute dystrophin deficiency

1/3300 newborn boys

            2/3 mothers are carriers

                        70% histologic abnormalities

                        50-90% elevated CK

                        5-10% clinical symptoms

Spectrum

Near identical to male Duchenne

Proximal myopathy +/- pseudohypertrophy (manifest <15 yo)

Autosomal recessive limb girdle muscular dystrophy (manifest < 20yo)

                        Weakness in 60% of carriers evident < 20yo

Pseudohypertrophy (80% carriers)

Cramps

Subclinical with elevated CK

Asymptomatic with normal CK

Familial manifesting carriers tend to be first degree relative (sister, mother, daughter) of male index case.

INVESTIGATIONS

FHx

ECG: RR¹ pattern

LM: variation in fibre size, degenerating fibres, increased fat & fibrous tissue

EM: widespread loss of myofilaments, Z line blurring, folding of basement membrane

EMG: low voltage polyphasic esp proximal muscles, no neurogenic pattern

CK: 50-90% sensitivity; average is 10.2 X normal

Immunohistochemical staining: mosaic pattern

cDNA +/- PCR: fails in 40% of cases to confirm gene defect

Endomyocardial biopsy: 60% sensitivity

Difficulties with pure genetic studies

XO/XX/XXX

XXY (theoretically)

Xp21 translocation