ESPE Abstracts

A 16 year old boy initially presented with short stature at age 6, with height <0.4th centile (HSDS -2.78). Bone age was 1.9 years delayed, and growth hormone deficiency was diagnosed after 2 stimulation tests. The rest of his pituitary function was normal. He never had pituitary imaging. Growth hormone treatment was started, and he had an excellent growth response with HSDS improving to -1.57 by 10 years. The growth hormone treatment was discontinued when the family relocated to UAE, but his growth velocity slowed to only 2.3 cm/year, and a year later the treatment was recommenced (HSDS -1.86). His current height at age 16 years is 164 cm (HSDS -1.24) and he is still growing well with height velocity 5.4 cm/year and predicted adult height of 168.1 cm. He had spontaneous puberty and the rest of his pituitary function remains normal. His father (158cm) and father’s brother (161cm) both received hormone treatment with HCG in adolescence for short stature but were diagnosed with growth hormone deficiency. His mother is 158cm, MPH 164.5 cm (-2.01 SD). His younger brother who is now 7 years, was initially seen from age 3 with short stature, height on 0.4th centile (HSDS -2.70) and height velocity 4.4 cm/year (-2.49 SD). He had the typical appearance of growth hormone deficiency with mid-facial crowding and increased adiposity. His bone age was 1.1 years delayed with low growth factors. He was confirmed to have growth hormone deficiency on stimulation testing with peak GH 5.36 ng/ml. MRI showed normal pituitary but identified a pineal gland cyst. He was commenced on growth hormone therapy at 4.5 years with a fantastic growth response, current HSDS -0.97 and HV 6.8 cm/year. As there were four individuals in the family with growth hormone deficiency, whole exome sequencing was undertaken in the older brother which revealed a previously undescribed heterozygous variant in the PROKR2 gene, which is a G protein-coupled receptor essential for the development of the olfactory bulb and sexual maturation and also neuronal migration. This gene has been associated with Kallman syndrome and variants have been found in patients with multiple pituitary hormone deficiencies. The older brother has had normal spontaneous puberty and both the father and the uncle were able to father children without any intervention, although they both had pubertal delay. We hypothesise that PROKR2 may also be relevant in familial isolated growth hormone deficiency.