Neurodevelopmental disorder with macrocephaly is a heterogeneous group of diseases. It has been reported that pathogenic variants in CHD3, CHD4, and GATAD2B are associated with this disease. They are components of the nucleosome remodeling and deacetylase (NuRD) complex. NuRD complex is a major regulator of gene expression involved in pluripotency, lineage commitment, and corticogenesis. In addition to macrocephaly and intellectual disability, CHD3 variants are associated with inguinal hernias and apraxia of speech; whereas CHD4 variants are associated with skeletal anomalies, deafness, and cardiac defects. GATAD2B-associated neurodevelopmental disorder (GAND) has phenotypic overlap with both of these disorders.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
LD90 Conditions with disorders of intellectual development as a relevant clinical feature
H02616 Neurodevelopmental disorder with macrocephaly
Weiss K, Terhal PA, Cohen L, Bruccoleri M, Irving M, Martinez AF, Rosenfeld JA, Machol K, Yang Y, Liu P, Walkiewicz M, Beuten J, Gomez-Ospina N, Haude K, Fong CT, Enns GM, Bernstein JA, Fan J, Gotway G, Ghorbani M, van Gassen K, Monroe GR, van Haaften G, Basel-Vanagaite L, Yang XJ, Campeau PM, Muenke M
Title
De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.
