ESPE Abstracts (2016) 86 RFC14.8

ACAN Mutations in Short Children Born SGA; Growth Response During GH Treatment with Additional GnRHa, and a Proposed Clinical Scoring System

Manouk van der Steena,b & Anita C.S. Hokken-Koelegaa,b


aDutch Growth Research Foundation, Rotterdam, The Netherlands; bErasmus University Medical Center- Sophia Children’s Hospital, Rotterdam, The Netherlands


Background: In children born SGA with persistent short stature, growth hormone (GH) treatment is an approved therapy for increasing adult height (AH). Some SGA children have an advanced bone age (BA) during GH. Heterozygous mutations in the ACAN-gene have been described in children with idiopathic short stature and advanced BA.

Objective and hypotheses: To assess growth during GH treatment with additional GnRHa treatment, in children with ACAN-gene mutations. To determine a clinical scoring system for ACAN-sequencing.

Method: Targeted ACAN-sequencing was performed in 22 short SGA children with advanced BA or midfacial hypoplasia.

Results: Four children, 3 boys and 1 girl, had an ACAN-gene mutation. All 4 children were treated with GH and received additional GnRHa treatment for 2 years from onset of puberty. Height SDS improved with 0.7 SDS. At AH, one girl was 5.2 cm taller than her mother and one boy was 8.0 cm taller than his father, parents had the same ACAN-gene mutation. In boys, treatment with GnRHa followed by Letrozole successfully delayed BA. ACAN-gene mutations were found in 21% of the children with an advanced BA of ≥0.5 years. Based on parental height SDS, height SDS and clinical characteristics of the child, a scoring system was composed which identified children with an ACAN-gene mutation with a sensitivity of 100%.

Conclusion: GH with additional GnRHa, in boys followed by Letrozole, might improve AH in children with ACAN-gene mutations. We propose a clinical scoring system to select patients for ACAN sequencing which should be based on advanced BA, parental height SDS and height SDS of the child.

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