Abstract 64: PRMT7 mutation related obesity -expanding the existing SBIDDS phenotype

Introduction - Paediatric obesity has increased substantially over the past four decades. The most common cause is exogenous obesity followed by endocrine and genetic aetiologies. Among genetic causes, mutations in MCR4, POMC and imprinted genes in 15q11, are common. We present here a case of obesity, growth hormone deficiency and hypothyroidism in a patient with homozygous PRMT7 mutation, a rare mutation that has been reported in less than 15 cases, and is causative of SBIDDS (short stature and brachydactyly, intellectual developmental disability, and seizures) phenotype. Case report: A 9 yearoldmale child, second bornof third degreeconsanguineous parents, presented to the Endocrine OPD with short stature. Birth weight was 2 kg. There was a history of delayed cry at birth, NICU stay and prolonged jaundice in the neonatal period. In the first month of life, a mid-sized PDA was detected and was conservatively managed. Spontaneous closure of PDA was noted at 3 years. There was history of developmental delay andmild intellectual deficit. Seizure disorder was diagnosed and he was on treatment. Excessive weight gain was observed at the age of 4 years. On examination, he was short with abdominal obesity, brachydactyly, simian crease and macroglossia. Height was below 3rd centile and weight at the 97th percentile. SMR was pre-pubertal:A1P2. Investigations confirmed growth hormone deficiency and primary hypothyroidism for which he was commenced on growth hormone therapy and levothyroxine. ONDST was negative. Genetic evaluation for Prader Willi syndrome and Angelman syndrome was negative. Whole exome sequencing revealed homozygosity for PRMT7 mutation with both parents heterozygous for the same gene mutation. His twin sibling was also found to be homozygous for the mutation. Discussion - PRMT7 is expressed ubiquitously in humans during development and into adulthood, and catalyzes the transfer of methyl groups playing a critical role in euchromatin maintenance, RNA splicing, cell growth and differentiation. PRMT7 also contributes to core skeletal integrity, through its regulation of the Wnt signaling pathway. Biallelicmutations in PRMT7 in humans are rare with only 15 reported cases and cause an autosomalRecessivecondition characterized by short stature and brachydactyly, intellectual developmental disability, and seizures (SBIDDS) syndrome. We report here some of the additional clinical features associated with this genetic condition-obesity, growth hormone deficiency and hypothyroidism. Further studies are required to delineate the natural history and molecular basis of this disorder, which may place it as one of the genetic etiologies of obesity.