Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes

Am J Med Genet A. 2018 May;176(5):1166-1174. doi: 10.1002/ajmg.a.38652.

Abstract

Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n = 11) and Hennekam syndrome (HS) (n= 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.

Keywords: ADAMTS3; CCBE1; DCHS1; FAT4; Hennekam syndrome; Van Maldergem syndrome; lymphedema.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Alleles*
  • Bone and Bones / abnormalities
  • Bone and Bones / diagnostic imaging
  • Brain / abnormalities
  • Brain / diagnostic imaging
  • Cadherins / genetics
  • Calcium-Binding Proteins / genetics
  • Child
  • Child, Preschool
  • Comparative Genomic Hybridization
  • Craniofacial Abnormalities / diagnosis*
  • Craniofacial Abnormalities / genetics*
  • Facies
  • Female
  • Foot Deformities, Congenital / diagnosis*
  • Foot Deformities, Congenital / genetics*
  • Genetic Association Studies* / methods
  • Genotype
  • Hand Deformities, Congenital / diagnosis*
  • Hand Deformities, Congenital / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Joint Instability / diagnosis*
  • Joint Instability / genetics*
  • Male
  • Mutation
  • Phenotype*
  • Radiography
  • Siblings
  • Tumor Suppressor Proteins / genetics

Substances

  • CCBE1 protein, human
  • Cadherins
  • Calcium-Binding Proteins
  • FAT4 protein, human
  • Tumor Suppressor Proteins

Supplementary concepts

  • Van Maldergem Wetzburger Verloes syndrome