ESPE Abstracts

Background: Rahman syndrome (RMNS) is an autosomal dominant overgrowth-intellectual disability syndrome caused by heterozygous mutations in H1-4 gene. Other frequent features reported in RMNS patients include: facial dimorphism, joint hypermobility, hypotonia, kyphoscoliosis, congenital heart defect, abnormal MRI image of brain and behaviour problems.

Case presentation: We report a 11-year-old girl born from 3^rd pathologic pregnancy of a diabetic mother with hypertension, first delivery by C-section at term with birth weight 4.2 kg (+2.23 SDS) and length 53 cm (+1.38 SDS). The patient has experienced neonatal hypoglycaemia and hyperbilirubinemia and due to failure to thrive, she was put on enteral feeding (by gastrosoma) until 1.5 year. She has developmental delay in motor/speech skills form birth. Family history: from mother’s side: three consecutive generations with diabetes developed around 40’s. The girl presented in our endocrine clinic at 6 years of: age because of progressive weight gain, increased appetite and tall stature. Her physical examination showed macrocephaly, broad prominent forehead, hypertelorism, low-set years, normal height and early-onset obesity (BMI +3.57 SDS). Laboratory tests, bone age and karyotype were normal. At age of 8 years and 4 months she developed polydipsia (>3 l/d), psychological/behaviour problems and mild intellectual disability (IQ 64). At the time the laboratory tests showed metabolic syndrome with elevated CRP and fatty liver and diabetes with hyperinsulinemia and Metformin was prescribed. Periodically HbA1c has been measured with the highest value of 8.4%. On brain MRI we found mild dilatation of lateral ventricles. Genetic analysis with Inviatae Overgrowth Syndrome Panel did not detect no pathogenic variants. At age of 10 years: the child was readmitted because of persistent severe obesity and developmental delay (IQ 64) and newly occurred thoracic scoliosis. Because of the spectrum of clinical symptoms with overgrowth and mild intellectual disability WES analysis was performed showing a novel heterozygous pathogenic variant of c.469_470insT, p.(Lys157Ilefs*59) in H1-4 gene, associated with RMNS.

Conclusion: As far as the knowledge of authors, this is the first reported paediatric patient with the reported mutation in RMNS that developed diabetes too. This case demonstrates the need to screen actively patients with obesity, overgrowth/tall stature and developmental delay/intellectual disability for RMNS.