TY - JOUR
T1 - 5q35 duplication syndrome
T2 - Narrowing the critical region on the distal side and further evidence of intrafamilial variability and expression
AU - van der Lugt, Neeltje Margreth
AU - Weerts, Marjolein J. A.
AU - Veenma, Danielle C. M.
AU - Lincke, Carsten R.
AU - Gischler, Saskia J.
AU - Alders, Marielle
AU - van Ierland, Yvette
N1 - Publisher Copyright: © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2022
Y1 - 2022
N2 - The key features of patients with a microduplication 5q35.2q35.3 (including the NSD1 gene) are short stature, microcephaly, mild developmental delay, behavioral problems, digital anomalies and congenital anomalies of internal organs. This core phenotype can be viewed as the reversed phenotype of Sotos syndrome, which is caused by a microdeletion in the same chromosomal region or a pathogenic variant in the NSD1 gene, and includes tall stature and macrocephaly, developmental delay, and epilepsy. Here, we report on a patient and his mother, both with a 5q35.2q35.3 duplication, adding a fifth family to the recently published overview of 39 patients of Quintero-Rivera et al. Our patient had several congenital anomalies, intrauterine growth restriction with a persisting short stature, while his mother was only mildly affected with decreased growth parameters. In addition, he had hemophagogocytic lymphohistiocytosis (HLH) triggered by Haemophilus influenzae and was recently diagnosed with Ewing sarcoma. Our cases carry the smallest duplication published (ca 332 kb, arr[hg19] 5q35.2q35.3(176493106-176824785)x3) further narrowing the distal side of the critical region of the 5q35.2q35.3 duplication. Besides broadening the clinical phenotypic spectrum, our report indicates that the 5q35.2q35.3 microduplication also shows a large intra-familial variability and expression.
AB - The key features of patients with a microduplication 5q35.2q35.3 (including the NSD1 gene) are short stature, microcephaly, mild developmental delay, behavioral problems, digital anomalies and congenital anomalies of internal organs. This core phenotype can be viewed as the reversed phenotype of Sotos syndrome, which is caused by a microdeletion in the same chromosomal region or a pathogenic variant in the NSD1 gene, and includes tall stature and macrocephaly, developmental delay, and epilepsy. Here, we report on a patient and his mother, both with a 5q35.2q35.3 duplication, adding a fifth family to the recently published overview of 39 patients of Quintero-Rivera et al. Our patient had several congenital anomalies, intrauterine growth restriction with a persisting short stature, while his mother was only mildly affected with decreased growth parameters. In addition, he had hemophagogocytic lymphohistiocytosis (HLH) triggered by Haemophilus influenzae and was recently diagnosed with Ewing sarcoma. Our cases carry the smallest duplication published (ca 332 kb, arr[hg19] 5q35.2q35.3(176493106-176824785)x3) further narrowing the distal side of the critical region of the 5q35.2q35.3 duplication. Besides broadening the clinical phenotypic spectrum, our report indicates that the 5q35.2q35.3 microduplication also shows a large intra-familial variability and expression.
KW - NSD1 gene
KW - chromosome 5q35
KW - duplication
KW - intrafamilial variable expression
UR - http://www.scopus.com/inward/record.url?scp=85143887630&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ajmg.a.63068
DO - https://doi.org/10.1002/ajmg.a.63068
M3 - Article
C2 - 36458506
SN - 1552-4825
JO - American journal of medical genetics. Part A
JF - American journal of medical genetics. Part A
ER -