ESPE Abstracts

Sclerosteosis is a rare autosomal recessive disorder characterized by progressive skeletal overgrowth and increased bone density. Loss of function mutations of SOST gene, coding for sclerostin, are linked to sclerosteosis. Sclerostin plays a critical role inhibiting osteoblastic activity and preventing excessive bone formation by antagonizing the Wnt signaling pathway. Sclerosteosis patients are often tall and have excessive body weight due to high skeletal weight. To our knowledge, around 96 patients have been reported worldwide, the majority from South Africa. No patients have been reported to have celiac disease (CD) as well. Due to the scarcity of cases, a knowledge gap exists as regards the molecular mechanisms of sclerosteosis, leading to unsatisfactory diagnostic and therapeutic strategies. We hereby report a SOST gene mutation causing sclerosteosis in an Egyptian patient with unusually poor growth and low bone density due to celiac disease.

Case summary: A 14-year-old girl diagnosed with intellectual disability (IQ test score 40) was referred to the Pediatric Endocrinology clinic for assessment of skeletal abnormalities, poor growth and delayed puberty. She was born to consanguineous parents and had 2 healthy siblings. There was no history of fractures. Her weight was 30 kg (-2.1 SD), height 152 cm (-1.36 SD), and head circumference 56 cm. She had normal arm span, and normal U:L ratio. She had dysmorphic facial features (large forehead, squared mandible, proptosis, crowded teeth), squint, elongated fingers, and dysplastic left index finger nail. She had breast Tanner I, and no pubic hair. Laboratory investigations showed iron deficiency anemia and vitamin D deficiency (25-OHD 7.56 ng/ml) with secondary hyperparathyroidism suggesting nutritional cause versus malabsorption. She had normal ESR, renal and liver functions. Celiac screen revealed highly positive anti-tissue transglutaminase IgA>100U/ml. Upper GI endoscopy and biopsy showing villous flattening and atrophy confirmed CD. Bone age was delayed and basal LH was pubertal. Skeletal survey showed mild C-shaped scoliosis at dorsolumbar spine, elongated cylindrical-shaped metacarpal and phalangeal metaphases with diffuse osteopenia. CT petrous bone showed marked medullary sclerosis and obliteration of medullary cavities suggesting sclerosing bony dysplasia. WES identified a homozygous pathogenic variant in SOST gene, which is associated with Sclerosteosis 1.

Conclusion: Sclerosteosis is a rare form of sclerosing bony dysplasia. Patients are usually tall with increased bone density. Thinking systematically in patients with unusual presentations can reveal new associations and may address knowledge gaps. The relation between sclerosteosis and CD needs to be further investigated.