Endocrine Abstracts

Introduction: Bloom syndrome (BS) is a rare autosomal recessive disorder caused by mutations in the BLM gene. Classic dysmorphic features include a long, narrow face, micrognathism and prominent nose and ears. Other features of the disease include pre- and post-natal growth failure, skin rash following sun exposure, hyper-pigmented areas or cafe-au-lait lesions, high-pitched voice and immunodeficiency. The most serious complication of BS is the significant increase in risk of malignancy due to genomic instability.

Case report: A 5-year-old girl presented to her local endocrinology clinic due to short stature. The patient was born at term (39/40 weeks) with a birth weight and length of 1580 g (SDS −4.7) and 44 cm (SDS −2.89), respectively (small for gestational age, SGA). From birth, she suffered recurrent infections of upper and lower respiratory tract, frequently requiring antibiotic treatment. She also developed hypothyroidism. Physical examination revealed significant short stature (height SDS −5.3) and low BMI (SDS −1.8). She had a long narrow face with micrognathia and café-au-lait spots were noted on her abdomen and right popliteal fossa. Baseline blood tests were unremarkable and both growth hormone (GH) stimulation and IGF-1 levels were within the normal range. As the patient was born SGA with no catch-up growth, she commenced GH therapy. Her growth velocity on hGH over a 9-month treatment period was 5.4 cm/year (5.8 cm/year prior to treatment). Given her growth failure and dysmorphic features, the patient was also referred for genetic testing. Whole exome sequencing identified a homozygous mutation in the BLM gene (91306246C>T, c.1933C>T, p.Q645*) which is recognised to cause Bloom syndrome. Due the increased risk of cancer development in Bloom syndrome, the decision was made to stop GH therapy.

Conclusions: Genetic diagnosis in children with short stature and concomitant dysmorphic features is important and in some rare syndromes GH therapy is contraindicated. Bloom syndrome causes pre- and post-natal growth failure and as such, may be referred to paediatric endocrinology. This case highlights the importance of detailed phenotypic assessment and referral for genetic testing in cases of undiagnosed syndromic short stature, particularly when considering GH therapy.