Genetic disorders with neuromuscular features
The majority of severe
neuromuscular disorders affecting infants and children have a genetic basis. In
addition to accurate assessment and ex-amination of the child, a detailed
family history and examination of parents may sometimes be very helpful in
establishing the diagnosis.
by a triplet repeat expansion (CTG)n in the myotonin gene on
chromosome 19q. Congenitally affected infants usually have a huge expansion of
the triplet repeat with >1000 repeats.
in affected babies born to women who also have myotonic dystrophy (an AD
disorder with onset usually in adult life), even when mild or undiagnosed.
there is polyhydramnios and at delivery the baby is floppy and may require
prolonged ventilatory support.
is usually possible by careful examination of the mother (percussion myotonia)
(also enquire if mother sleeps with eyes open) and analysis of a DNA sample
from the infant.
mortality is 720%. Survivors have static or slowly progressive muscle weakness.
Many have associated moderate intellectual impairment.
Affects 71/3500 male births: DMD is the most common and severe form of childhood muscular dystrophy.
by mutations (deletions, duplications, and point mutations) in the dystrophin
gene on chromosome Xq28.
with developmental delay, especially late walking and speech delay. In the
early phase of the disease, boys have difficulty rising from the floor (Gower’s
manoeuvre sign where the child climbs up his thighs with his hands to get up
off the floor). Later there is early loss of ambulation (mean age 79 years).
Affected boys develop a progressive cardiomyopathy. 730% of boys with DMD have
a mild learning disability that is not progressive.
CK is grossly elevated, usually >10 times normal levels. Diagnosis is often
possible by genetic testing, avoiding the need for muscle biopsy.
follows X-linked recessive inheritance and expert genetic counselling is an
essential part of management.
Death from cardiorespiratory
failure or infection usually occurs in the late teens or early 20s.
disorder caused by bi-allelic mutation in the SMN gene on 5q13. 795% of infants with type 1 SMA are homozygously
deleted for exon 7 of the SMN1 gene.
severe cases, babies usually feed normally for the first few weeks with the
earliest sign often being of a tiring infant who does not finish his feed.
Clinical examination may show fasciculations of the tongue, an important clinical
symmetrical proximal muscle weakness as a consequence of degeneration of the
anterior horn cells of the spinal cord. Intelligence is unaffected.
Type 1 SMA (severe)—onset in first few months of
life. Never able to sit or walk.
Usually die from respiratory failure by age 6–12mths.
Type 2 SMA (intermediate)—onset before age 18mths. Able to
sit, but not to walk unaided.
Survival into adult life is usual.
Type 3 SMA (mild)—onset of proximal muscle weakness
after age 2yrs. Ability to walk
independently initially; survival into adult life.
Diagnosis can be made by molecular