201. Clinical Characteristics of Pathogenic <italic>ACAN</italic> Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data.
- Author
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Renes, Judith S., Reedijk, Ardine M.J., Losekoot, Monique, Kant, Sarina G., Van der Steen, Manouk, Van der Kaay, Danielle C.M., Hokken-Koelega, Anita C.S., Van Duyvenvoorde, Hermine A., and de Bruin, Christiaan
- Abstract
Heterozygous variants in theIntroduction: ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA). The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygousMethods: ACAN variant. Thirty-six subjects (23 boys, 13 girls) withACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children. We identified 25 different heterozygousResults: ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was −2.6 SDS (−3.2 to −2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncatingACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (−2.8 SDS and −2.1 SDS, respectively,p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9–1.4). In pubertal children, height SDS remained relatively stable. The phenotype of subjects with pathogenic heterozygousConclusion: ACAN variants is highly variable, and genetic testing forACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children withACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment. [ABSTRACT FROM AUTHOR]- Published
- 2024
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