Clinical Characteristics of Pathogenic ACAN Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data.
Horm Res Paediatr
; : 1-14, 2024 Jan 17.
Article
en En
| MEDLINE
| ID: mdl-38232712
ABSTRACT
INTRODUCTION:
Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA).METHODS:
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 heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children.RESULTS:
We identified 25 different heterozygous 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 â¼20%, no specific features were reported. Subjects with a truncating ACAN 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.CONCLUSION:
The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN 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 with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Horm Res Paediatr
Asunto de la revista:
ENDOCRINOLOGIA
/
PEDIATRIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos