TY - JOUR
T1 - Growth charts for Marfan syndrome in the Netherlands and analysis of genotype–phenotype relationships
AU - Lauffer, Peter
AU - Pals, Gerard
AU - Zwinderman, Aeilko H.
AU - Postema, Floor A. M.
AU - Baars, Marieke J. H.
AU - Dulfer, Eelco
AU - Hilhorst-Hofstee, Yvonne
AU - Houweling, Arjan C.
AU - Kempers, Marlies
AU - Krapels, Ingrid P. C.
AU - van de Laar, Ingrid M. B. H.
AU - Loeys, Bart
AU - Spaans, Alexander M. J.
AU - Warnink-Kavelaars, Jessica
AU - de Waard, Vivian
AU - Wit, Jan M.
AU - Menke, Leonie A.
N1 - Funding Information: This study was supported by grants of the Dutch patient association “Contactgroep Marfan Nederland” and the Emma Children's Hospital Foundation (WAR2017‐24). Funding Information: The authors thank Annelies van der Hulst, pediatric-cardiologist; Elke Kraal-Biezen, ophthalmologist; Madeleine Tilburgs, pediatric assistant; and Alessandra Maugeri, molecular geneticist, for their important roles in the Amsterdam Expert Center for children with Marfan syndrome and related disorders. Publisher Copyright: © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2023/2
Y1 - 2023/2
N2 - To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect of FBN1 variant type (haploinsufficiency [HI]/dominant negative [DN]) on growth, and compare MFS-related height increase across populations. Height and weight data of individuals with MFS aged 0–21 years were retrospectively collected. Generalized Additive Models for Location, Scale and Shape (GAMLSS) was used for growth chart modeling. To investigate genotype–phenotype relationships, FBN1 variant type was included as an independent variable in height-for-age and BMI-for-age models. MFS-related height increase was compared with that of previous MFS growth studies from the United States, Korea, and France. Height and weight data of 389 individuals with MFS were included (210 males). Height-for-age, BMI-for-age, and weight-for-height charts reflected the tall and slender MFS habitus throughout childhood. Mean increase in height of individuals with MFS compared with the general Dutch population was significantly lower than in the other three MFS populations compared to their reference populations. FBN1-HI variants were associated with taller height in both sexes, and decreased BMI in females (p-values <0.05). This Dutch MFS growth study broadens the notion that genetic background and MFS variant type (HI/DN) influence tall and slender stature in MFS.
AB - To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect of FBN1 variant type (haploinsufficiency [HI]/dominant negative [DN]) on growth, and compare MFS-related height increase across populations. Height and weight data of individuals with MFS aged 0–21 years were retrospectively collected. Generalized Additive Models for Location, Scale and Shape (GAMLSS) was used for growth chart modeling. To investigate genotype–phenotype relationships, FBN1 variant type was included as an independent variable in height-for-age and BMI-for-age models. MFS-related height increase was compared with that of previous MFS growth studies from the United States, Korea, and France. Height and weight data of 389 individuals with MFS were included (210 males). Height-for-age, BMI-for-age, and weight-for-height charts reflected the tall and slender MFS habitus throughout childhood. Mean increase in height of individuals with MFS compared with the general Dutch population was significantly lower than in the other three MFS populations compared to their reference populations. FBN1-HI variants were associated with taller height in both sexes, and decreased BMI in females (p-values <0.05). This Dutch MFS growth study broadens the notion that genetic background and MFS variant type (HI/DN) influence tall and slender stature in MFS.
KW - Marfan syndrome
KW - dominant-negative variant
KW - growth charts
KW - haploinsufficiency variant
KW - height
KW - weight
UR - http://www.scopus.com/inward/record.url?scp=85143231400&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajmg.a.63047
DO - https://doi.org/10.1002/ajmg.a.63047
M3 - Article
C2 - 36380655
SN - 1552-4825
VL - 191
SP - 479
EP - 489
JO - American journal of medical genetics. Part A
JF - American journal of medical genetics. Part A
IS - 2
ER -