Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4
- Resource Type
- Authors
- Denise Horn; Pablo Villavicencio-Lorini; Randi Koll; Marc Trimborn; Stefan Mundlos; Eva Klopocki
- Source
- European journal og human genetics : EJHG ; the official journal of the European Society of Human Genetics
- Subject
- Adult
Male
Adolescent
Chromosome Disorders
Biology
Fibrous Dysplasia, Polyostotic
Histone Deacetylases
Article
Intellectual Disability
Genetics
medicine
Humans
Child
Genetics (clinical)
Aged
Sequence Deletion
Comparative Genomic Hybridization
Fibrous dysplasia
Brachydactyly
Chromosome
Middle Aged
medicine.disease
HDAC4
Phenotype
Pedigree
Repressor Proteins
Child, Preschool
Chromosomes, Human, Pair 2
Chromosomal region
Female
Chromosome Deletion
Haploinsufficiency
Comparative genomic hybridization
- Language
- ISSN
- 1476-5438
1018-4813
Deletions of the chromosomal region 2q37 cause brachydactyly-mental retardation syndrome (BDMR), also known as Albright hereditary osteodystrophy-like syndrome. Recently, histone deacetylase 4 (HDAC4) haploinsufficiency has been postulated to be the critical genetic mechanism responsible for the main clinical characteristics of the BDMR syndrome like developmental delay and behavioural abnormalities in combination with brachydactyly type E (BDE). We report here on the first three generation familial case of BDMR syndrome with inheritance of an interstitial microdeletion of chromosome 2q37.3. The deletion was detected by array comparative genomic hybridization and comprises the HDAC4 gene and two other genes. The patients of this pedigree show a variable severity of psychomotor and behavioural abnormalities in combination with a specific facial dysmorphism but without BDE. Given that only about half of the patients with 2q37 deletions have BDE; we compared our patients with other patients carrying 2q37.3 deletions or HDAC4 mutations known from the literature to discuss the diagnostic relevance of the facial dysmorphism pattern in 2q37.3 deletion cases involving the HDAC4 gene. We conclude that HDAC4 haploinsufficiency is responsible for psychomotor and behavioural abnormalities in combination with the BDMR syndrome-specific facial dysmorphism pattern and that these clinical features have a central diagnostic relevance.European Journal of Human Genetics advance online publication, 28 November 2012; doi:10.1038/ejhg.2012.240.