Endocrine Abstracts

Introduction: Noonan syndrome (NS) (OMIM 163950) is an autosomal dominant clinically heterogeneous disorder characterised by multisystem involvement. Mutations in genes in the RAS/MAP signaling pathways are known to be responsible for ~70% of cases of NS. We report an infant with NS with early onset fragility fractures.

Case report: A 15-month-old male infant with a history of atopic eczema, sparse hair on the scalp, slow motor development, feeding difficulties, faltering growth, congenital cardiac problems (atrial septal defect, pulmonary valve stenosis and branch pulmonary artery stenosis) and macrocephaly, presented with a painful and swollen left leg. Radiographs revealed an undisplaced spiral fracture of the mid shaft of the left femur. The skeletal survey showed generalised osteopenia and anterior wedging of T12 vertebral body. MRI of the spine showed compression fractures of multiple mid and lower thoracic vertebral bodies. His serum concentrations of calcium, phosphate, alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D were within normal limits. With history of significant unexplained fractures child safeguarding procedures were initiated. The infant was thought to have clinical features of NS; genetic testing revealed a heterozygous mutation in SHOC2 c.4A>G (p.ser2Gly), confirming the diagnosis of Noonan syndrome with loose anagen hair. An unlabelled trans-iliac bone biopsy revealed marked cortical and trabecular osteopenia with relatively normal osteoblastic and osteoclastic activity. The patient has been commenced on cyclical intravenous Pamidronate therapy in order to reduce his risk of fracture.

Discussion: Generalised osteopenia is a recognised feature in RASopathies, such as neurofibromatosis type 1 and Costello syndrome. Stevenson et al. (Clinical Genetics 2011 80(6) 566–73) have shown that NF subjects have increased bone resorption as measured by urinary excretion of pyridinium crosslinks. However, to the best of our knowledge, osteopenia with early onset fragility fractures of axial and appedicular skeleton have not been previously described in NS.