Monogenic Short Stature and the Promise of Identifying Genetic Etiologies

Endocrinology Advisor
15 May, 2019 ,

At the recent Pediatric Academic Societies Meeting Dr Andrew Dauber presented data from  use of growth hormone in children who have aggrecan deficiency. The interim data showed that aggrecan deficiency receiving recombinant human GH therapy for 6 months had better velocity and mean change in height. 

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At the 2019 meeting of the Pediatric Endocrine Society (PES), held in conjunction with the Pediatric Academic Societies Meeting, April 24 to May 1, in Baltimore, Maryland, Dr Andrew Dauber, division chief of endocrinology at Children’s National Health System in Washington, DC, presented data from a trial focused on the use of growth hormone (GH) in children with aggrecan deficiency.

The ongoing study includes a small cohort of prepubertal children age ≥3 years who have heterozygous pathogenic mutations in the ACANgene resulting in deficiency of aggrecan, a proteoglycan component of growth plate cartilage. Characterized by Dr Dauber and colleagues in a 2016 study published in The Journal of Clinical Endocrinology & Metabolism, aggrecan deficiency resulting from ACAN mutations causes premature fusion of the growth plates and often significant short stature.

Interim data presented at the PES meeting showed that participants with aggrecan deficiency receiving recombinant human GH therapy for 6 months (n = 6) had improvements in height velocity (9.5 cm/yr) and mean change in height standard deviation (SD) scores (+0.46) from baseline. Patients receiving GH for 12 months (n = 4) had an even greater mean change in height SD scores (+0.67). There were no unexpected adverse events.

The study also investigated the extent of joint involvement in aggrecan deficiency in the pediatric patients and their affected relatives (n = 18). Of note, 2 cases of osteochondritis dissecans of the knees were reported in asymptomatic patients age 11 and 12 years and 6 cases of osteoarthritis were found in adult family members. This apparent higher risk for joint complications warrants routine evaluation in patients who have pathogenic ACAN mutations.