ESPE Abstracts (2022) 95 P1-127

ESPE2022 Poster Category 1 Growth and Syndromes (85 abstracts)

Treatment response to growth hormone in a patient with heterozygous ROR2 mutation

Nur Berna Celik 1 , Abdullah Sezer 2 , Selin Elmaogullari 1 , Senay Savas-Erdeve 1 & Semra Cetinkaya 1

1University of Health Sciences, Dr. Sami Ulus Maternity and Children's Research and Training Hospital, Clinic of Pediatric Endocrinology, Ankara, Turkey; 2University of Health Sciences Turkey, Dr. Sami Ulus Maternity and Children's Research and Training Hospital, Clinic of Genetics, Ankara, Turkey

Introduction: ‘Receptor tyrosine kinase-like orphan receptor 2 (ROR2)’ is a transmembrane protein tyrosine kinase encoded by the ROR2 gene. Pathogenic mutations in ROR2 are involved in two diseases: biallelic loss-of-function mutations in Robinow syndrome and monoallelic gain-of-function mutations in brachydactyly type B1. Recently, monoallelic loss-of-function mutations in ROR2 have been reported as a cause of isolated short stature. Here we reported the treatment response of growth hormone (GH) therapy in a patient with monoallelic loss-of-function mutation in ROR2.

Case: A 8.3 years old girl was referred for short stature. There was no history of chronic diseases, malabsorptive symptoms, feeding difficulties. She was born with a weight of 3160 gr (-0.4 SDS) at term after an uneventful pregnancy to parents who were nonconsanguineous. Her developmental milestones were normal. Her mother’s and father’s heights were 155 cm (-1.4 SDS) and 148 cm (-4.6 SDS, arm-span 147 cm) (midparenteral height was 145 cm -3.1 SDS). Her height was 111.7 cm (-3.07 SDS), weight was 17.7 kg (-3.6 SDS). Bone age was 6.8 years. She had proportional severe short stature. She had no dysmorphic features except high-arched eyebrows and a pointed chin. She was prepubertal. Total blood count and blood chemistry analysis were normal, and celiac antibodies were negative. At the age of 9.5 years, her growth velocity (GV) was 4 cm/year (her height was 116.9 cm (-3.1 SDS), and bone age was 7.8 years). GH stimulation tests with L-dopa and clonidine showed peak GH responses of 2.8 and 9.8 ng/ml and daily subcutaneous rhGH was started at a dose of 0.2 mg/kg/week. Her GV was 7.9 cm for the first year. However, despite the improvement of GV, her bone age accelerated even more. After three years of rhGH, at the age of 12.5 years, her height was 137.9 cm (-2.8 SDS), bone age was 13 years, and puberty was at Tanner stage 3. Predicted adult height was 143.9 cm (-3.2 SDS) which was compatible with midparenteral height. We conducted a genetic analysis due to family history suggesting monogenic causes, and poor response to rhGH. Next-generation sequencing revealed a missense monoallelic c.315G>T(p.Glu105Asp) mutation in ROR2.

Conclusion: ROR2 has a significant role in the formation and development of chondrocytes and bone by a mechanism other than the GH pathway. This pathway explains the poor response to rhGH in our patient. So, genetic testing is important for guiding the therapy.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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