Abstract
Protein arginine methyltransferase 7 (PRMT7) pathogenetic variants have been associated with the human disorder of Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS). Only 15 cases have been described in the literature. Here we report two female dizygotic twins with novel compound heterozygous deleterious variants of PRMT7 and describe the associated endocrine manifestations and short-term response to recombinant growth hormone (rGH) treatment. They were born at 36 + 3 weeks from a dichorionic diamniotic twin pregnancy. Twin A was appropriate for gestational age while Twin B was small for gestational age. Whole exome sequencing analyses showed the same novel compound heterozygous genetic defects in the PRMT7 gene (c.1220 G > A of maternal origin; c.1323 + 2 T > G of paternal origin, Fig. 1). Due to severe short stature and growth impairment, at six years of age, endocrine investigations were performed to rule out growth hormone (GH) deficiency, and revealed GH deficiency (GHD) in Twin A and an appropriate GH response in Twin B. Therefore, both started rGH, albeit at different dosages according to the underlying diagnosis. Both showed a satisfactory short-term response to treatment with height gain (∆HT) of +0.52 SDS (Twin A) and +0.88 SDS (Twin B) during the first year. In conclusion, our findings expand the knowledge about the endocrine manifestations associated with PRMT7 pathogenetic variants, including GH deficiency and rGH response. Further studies are needed to investigate long-term outcomes and establish whether PRMT7 genetic defects can be included among syndromic short stature treatable with rGH.