Bone Abstracts

Background: Duchenne muscular dystrophy (DMD) is characterised by progressive muscle weakness leading to loss of mobility, cardiomyopathy, and respiratory insufficiency. Typical initial manifestation in boys (X-linked disorder) comprises proximal muscle weakness and calf hypertrophy. Osteogenesis imperfecta (OI) is a clinically heterogenous heritable connective tissue disorder with increased bone fragility. Fractures rise from little or no apparent trauma.

Presenting problem: We put forward a five-years-old patient with ‘double trouble’: DMD and OI. He is a child of unrelated parents. His paternal family history was positive for OI, including the patient’s father, grandmother and great-grandfather.

Clinical management: Our patient was presented at 11 months of age due to high liver blood tests following gastroenteritis. Investigation revealed elevated creatinkinase. Hypotonia, diminished deep tendon reflexes, and calf hypertrophy arose about the possibility of muscular dystrophy. DNA analysis confirmed deletion of exons 48–52 in the dystrophin gene consistent with diagnosis of DMD.

At 2 years of age, humeral fracture appeared with unknown mechanism and 1 month later he sustained tibial fracture due to inappropriate trauma mechanism. Targeted genetic testing identified causative mutation c.2667+5G>A in the patient’s COL1A1 gene. This is a type of splice site mutation due to missing donor splicing site, which has not been described yet. However, similar mutation types were described in other introns of the gene. Lumbar spine bone densitometry revealed excessively low bone mineral density (z-score −3.95, adjusted for height age). 2 years of treatment with intravenous pamidronate and 1-α-hydroxy vitamin D resulted in significant improvement (adjusted z-score −0.93). Height gain is 16 cm and weight gain 3.4 kg within 27 months. He is able to walk 300 m without rest. Hypotonia persists as well as low tendon reflexes, calf pseudohypertrophy, and positive Gower’s sign. No further fracture appeared.

Discussion: As dystrophin gene mutations may be carried through an unaffected mother (or as ‘de novo’ mutation), the family history of DMD is frequently negative. Mutations in COL1A1 are mostly inherited through an autosomal dominant pattern with positive family history of OI.

Muscle weakness, mobility limitations and developmental motor delays could be shared by both diseases resulting in diagnostic difficulties.

Disclosure: The authors declared no competing interests.