MD Diagnoses Sometimes Warrant
A Closer Look
Getting the right diagnosis is important to understand inheritance
risks and also because some medications now in development are
designed to treat specific types of mutations. Sometimes, a
diagnosis warrants a closer look.
DMD, BMD or LGMD?
Marianne Schwartz at National University Hospital in Copenhagen,
Denmark, screened DNA samples from 102 male patients who were
given a diagnosis of Duchenne or Becker muscular
dystrophy (DMD or BMD) between 1988 and
2004 but in whom no missing or duplicated parts of the dystrophin
gene had been identified. Missing parts of the gene for this
muscle protein gene (deletion mutations) or duplicated parts
(duplication mutations) are found in approximately 60 percent
of DNA samples in boys with signs and symptoms of DMD or BMD.
Small flaws (point mutations) in the dystrophin gene are thought
to be responsible for most of the remaining 40 percent. But,
as a paper in the May 10 issue of Neurology demonstrates, it’s
now clear that sometimes the flaw isn’t in the dystrophin
gene at all, but in another gene entirely.
Of the 102 samples with a tentative diagnosis of DMD or BMD
that the Danish investigators re-examined, 13 had disease-causing
mutations in a gene that gives rise to fukutin-related protein
(FKRP), on chromosome 19. Their diagnoses have been revised
to type 2I limb-girdle muscular dystrophy (LGMD), which
has a different inheritance pattern from the X-chromosome-linked
DMD and BMD.
FSHD or Not?
In a study conducted at the University of Connecticut School
of Medicine in Farmington and published in the March issue of
the Journal of Clinical Neuromuscular Disease, investigators
found that facioscapulohumeral muscular dystrophy (FSHD) can, at the less severe end of its spectrum, be misdiagnosed
as LGMD or other muscle disorders.
FSHD results from a shorter than average DNA segment on chromosome
4, and those with chromosome 4 segments that were near the normal
range had “classic” FSHD symptoms only 18 percent
of the time. |
