Growth, body composition, and endocrine-metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies.
9q34.3
EHMT1
Kleefstra syndrome
MDEM
body composition
growth
metabolism
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
29 Dec 2023
29 Dec 2023
Historique:
revised:
17
10
2023
received:
09
08
2023
accepted:
27
10
2023
medline:
29
12
2023
pubmed:
29
12
2023
entrez:
29
12
2023
Statut:
aheadofprint
Résumé
Mendelian neurodevelopmental disorders caused by variants in genes encoding chromatin modification can be categorized as Mendelian disorders of the epigenetic machinery (MDEMs). These disorders have significant overlap in molecular pathways and phenotypes including intellectual disability, short stature, and obesity. Among the MDEMs is Kleefstra syndrome (KLFS), which is caused by haploinsufficiency of EHMT1. Preclinical studies have identified metabolic dysregulation and obesity in KLFS models, but proper clinical translation lacks. In this study, we aim to delineate growth, body composition, and endocrine-metabolic characteristics in a total of 62 individuals with KLFS. Our results revealed a high prevalence of childhood-onset overweight/obesity (60%; 28/47) with disproportionately high body fat percentage, which aligns perfectly with previous preclinical studies. Short stature was common (33%), likely due to advanced skeletal maturation. Endocrine-metabolic investigations showed thyroid dysregulation (22%; 9/41), elevated triglycerides, and decreased blood ammonia levels. Moreover, hand radiographs identified decreased bone mineralization (57%; 8/14) and negative ulnar variance (71%; 10/14). Our findings indicate a high (cardio)metabolic risk in KLFS. Therefore, we recommend monitoring of weight and endocrine-metabolic profile. Supporting a healthy lifestyle and screening of bone mineralization is advised. Our comprehensive results support translational research and contribute to a better understanding of MDEM-associated phenotypes.
Identifiants
pubmed: 38155610
doi: 10.1002/ajmg.a.63472
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : ZonMw
Pays : Netherlands
Organisme : Dutch Research Council
ID : 09150181910022
Pays : Netherlands
Organisme : Dutch Research Council
ID : 1160.18.320
Pays : Netherlands
Organisme : Dutch Research Council
ID : 015.014.036
Pays : Netherlands
Informations de copyright
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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