ESPE Abstracts (2021) 94 P1-122

ESPE2021 ePoster Category 1 Growth A (10 abstracts)

Short stature in Protein Arginine Methyltransferase 7 (PRMT7) mutations: first evidences of growth response to rGH treatment

Giulia Rodari 1,2 , Federico Giacchetti 2 , Roberta Villa 3 , Giulietta Scuvera 3 , Silvana Gangi 4 , Matteo Porro 5 , Maria Francesca Bedeschi 3 , Eriselda Profka 1 , Alberta Dall’Antonia 2 , Maura Arosio 1,2 & Claudia Giavoli 1,2

1Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Medical Genetic Unit, Milan, Italy; 4Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy; 5Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pediatric Physical Medicine & Rehabilitation Unit, Milan, Italy

Protein arginine methyltransferase 7 (PRMT7), a member of a family of enzymes that catalyse the transfer of methyl groups from S-adenosyl-L-methionine to nitrogen atoms on arginine residues, is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 12 patients with homozygous/compound heterozygous mutations in PRMT7 gene have been described defining the human disorder known as Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS) (OMIM #617157). Short stature is probably a pathognomonic feature of SBIDDSs, although growth hormone deficiency (GHD) has never been described before. We report the endocrine manifestations and rGH (recombinant growth hormone) response of two female dizygotic twin sisters (Twin A and Twin B), born small for gestational ages, with novel biallelic variants in PRMT7. Whole exome sequencing analyses showed the same compound heterozygous mutation in PRMT7 gene (p.Cys407Tyr of maternal origin; c.1323+2T>G of paternal origin) in both twins. Due to severe short stature and growth impairment (Height Twin A -2.75 SDS; Height Twin B -2.95 SDS), at six years of age, endocrine investigations to rule out GHD were performed, showing GHD in Twin A (peak GH at arginine test: 4.61 µg/l; peak GH at glucagon test: 5.14 µg/l; IGF-I 47 ng/ml, -2.19SDS) and an appropriate GH response in Twin B (peak GH at arginine test: 11.8 µg/l; IGF-I 52 ng/ml, -2.05SDS). No other pituitary deficiency was found.

They were started on rGH at different dosages according to the underlying diagnosis: replacement dosage of 0.025 mg/kg/day in Twin A and 0.035 mg/kg/day in Twin B, as expected in SGA with birth weight <-2SDS.

After one year therapy, Twin A, diagnosed having GHD, gained 7.5 cm, with a growth velocity (GV) of 2.06SDS for her age and a height gain (∆HT) of 0.52SDS (from HT -2.75SDS to HT -2.23SDS according to Cacciari Growth Charts). On the other hand, Twin B, treated as short stature in SGA, gained even 9.4 cm, showing a GV of 4.1SDS for sex and age and ∆HT of 0.88SDS (from HT -2.95SDS to HT -2.07SDS).

In conclusion, our findings provide further data of endocrine manifestations associated with PRMT7 mutations including GHD. Considering the short-term good response to rGH, further studies are needed in these patients to confirm outcomes in the long-term and ∆HT at adult height.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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