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Paediatrics: Genetic disorders with neuromuscular features

The majority of severe neuromuscular disorders affecting infants and children have a genetic basis.

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.


Congenital myotonic dystrophy


   Caused 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.


   Occurs 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.


   Typically, there is polyhydramnios and at delivery the baby is floppy and may require prolonged ventilatory support.


   Diagnosis 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.


   Neonatal mortality is 720%. Survivors have static or slowly progressive muscle weakness. Many have associated moderate intellectual impairment.


Duchenne muscular dystrophy


   Affects 71/3500 male births: DMD is the most common and severe form of childhood muscular dystrophy.


   Caused by mutations (deletions, duplications, and point mutations) in the dystrophin gene on chromosome Xq28.


   Presents 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.


   Serum CK is grossly elevated, usually >10 times normal levels. Diagnosis is often possible by genetic testing, avoiding the need for muscle biopsy.


   DMD 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.

Spinal muscular atrophy


An AR 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.

In 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 indicator.


Develop symmetrical proximal muscle weakness as a consequence of degeneration of the anterior horn cells of the spinal cord. Intelligence is unaffected.


·Several types:


   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 genetic testing.


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