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Proximal Deletions of 14q32.2 Result in Severe Neurodevelopmental Outcomes, Congenital Anomalies, and Dysmorphic Features
Author(s) -
Black Jennifer,
Lebel Robert Roger,
Garg Ria,
Koning Maayke,
Ruivenkamp Claudia,
Goel Himanshu,
Smith Scott C.
Publication year - 2025
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.64042
Subject(s) - genetics , hypotonia , phenotype , intellectual disability , medicine , karyotype , biology , chromosome , pediatrics , gene
ABSTRACT Deletions of chromosome 14q32.2 often involve the imprinted region of chromosome 14, giving rise to paternal or maternal UPD(14)‐like phenotypes. A few individuals with deletions that spare the imprinted region have been reported, with significant variability in deletion size and gene involvement. Four patients with proximal deletions of 14q32.2 were gathered from the primary authors' clinic or through the DECIPHER database. Informed consent for inclusion in this study was obtained from all participants. A retrospective chart review was performed, and medical history records were compiled and analyzed. We report four patients with similar deletions of 14q32.2, three of whom do not involve the imprinted region. These deletions overlapped for 13 different genes, three of which are associated with autosomal dominant conditions: BCL11B, CCNK, and YY1. All four patients presented with prenatal and/or postnatal growth restriction, feeding problems, congenital urogenital anomalies, hypotonia, severe intellectual and developmental disability, and similar dysmorphic features. We propose that deletions involving BCL11B, CCNK, and YY1 result in a discrete clinical entity entailing a severe neurodevelopmental phenotype, characteristic facial features, and congenital anomalies. We propose the nomenclature of proximal 14q32.2 deletion syndrome.