Introduction: Chromosome 18 rearrangements are postulated to be associated with short stature, of uncertain pathophysiology.
Methods: Retrospective case review (short stature with chromosome 18 rearrangement), investigation for GH deficiency (peak GH <7 μg/l on glucagon or ITT, unless otherwise indicated) and determining response to GH treatment.
Results: In 13 year six such cases were referred from the geneticists, mean referral age, 3.3 years (1.210.5 years) with mean parental adjusted (PA) height SDS of −3.8 (−8.6 to −0.6). Cases 1 and 2 were associated with 18 p deletions alone, presenting with PA height SDS of −3.5 and −2.6 and normal peak GH on stimulation (16 and 9.2 μg/l) respectively. GH treatment was not indicated and PA height SDS demonstrates ongoing short stature (case 1: −2.8, case 2: −3.4).
Four patients met criteria for GH treatment for GH deficiency. Case 3 had an 18 q deletion, PA height SDS −0.6 with poor height velocity (2.5 cm/year) and suboptimal GH response to stimulation (6.2 μg/l). Case 46 were associated with ring chromosome 18 with18 p/q deletions. In all cases suboptimal GH responses were identified on stimulation (cases 4 and 5: 4.9 μg/l, 5 μg/l respectively; case 6: 11 mu/l (peak <20 mu/l on arginine testing). In cases 5 and 6, a small pituitary was identified on imaging. With GH treatment a significant increase in PA height SDS (from presentation to most recent review) is observed in all cases, P=0.04 (paired t-test, one-tailed), all showing >50% height velocity increase in 1 year.
Conclusion: In our case series, 18 p deletions alone were not associated with GH deficiency-related short stature. 18 q deletions and ring chromosome 18 abnormalities with 18 p/q deletions were associated with GH deficiency, all showing good response to treatment. We propose that GH deficiency is investigated in all individuals with chromosome 18 rearrangements and short stature, particularly 18q deletions and ring chromosome18 abnormalities.
12 - 14 Nov 2014
British Society for Paediatric Endocrinology and Diabetes