title: The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.
abstract: Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic features in these patients. In this study, we report the molecular and clinical characterisation of nine new 2q23.1 deletion patients and a clinical update on two previously reported patients. All patients were mentally retarded with pronounced speech delay and additional abnormalities including short stature, seizures, microcephaly and coarse facies. The majority of cases presented with stereotypic repetitive behaviour, a disturbed sleep pattern and a broad-based gait. These features led to the initial clinical impression of Angelman, Rett or Smith-Magenis syndromes in several patients. The overlapping 2q23.1 deletion region in all 15 patients comprises only one gene, namely, MBD5. Interestingly, MBD5 is a member of the methyl CpG-binding domain protein family, which also comprises MECP2, mutated in Rett's syndrome. Another gene in the 2q23.1 region, EPC2, was deleted in 12 patients who had a broader phenotype than those with a deletion of MBD5 only. EPC2 is a member of the polycomb protein family, involved in heterochromatin formation and might be involved in causing MR. Patients with a 2q23.1 microdeletion present with a variable phenotype and the diagnosis should be considered in mentally retarded children with coarse facies, seizures, disturbed sleeping patterns and additional specific behavioural problems.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Bregje W M
authors.initials: BW
authors.lastname: van Bon
authors.forename: David A
authors.initials: DA
authors.lastname: Koolen
authors.forename: Louise
authors.initials: L
authors.lastname: Brueton
authors.forename: Dominic
authors.initials: D
authors.lastname: McMullan
authors.forename: Klaske D
authors.initials: KD
authors.lastname: Lichtenbelt
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Adès
authors.forename: Gregory
authors.initials: G
authors.lastname: Peters
authors.forename: Kate
authors.initials: K
authors.lastname: Gibson
authors.forename: Susan
authors.initials: S
authors.lastname: Moloney
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.forename: Tiziano
authors.initials: T
authors.lastname: Pramparo
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dalla Bernardina
authors.forename: Leonardo
authors.initials: L
authors.lastname: Zoccante
authors.forename: Umberto
authors.initials: U
authors.lastname: Balottin
authors.forename: Fausta
authors.initials: F
authors.lastname: Piazza
authors.forename: Vanna
authors.initials: V
authors.lastname: Pecile
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Veronica
authors.initials: V
authors.lastname: Guerci
authors.forename: Marleen
authors.initials: M
authors.lastname: Kets
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Arjan P
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Nicole
authors.initials: N
authors.lastname: de Leeuw
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.forename: Jayne
authors.initials: J
authors.lastname: Antony
authors.forename: Santina
authors.initials: S
authors.lastname: Reitano
authors.forename: Daniela
authors.initials: D
authors.lastname: Luciano
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics; D002585:Cesarean Section; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007363:Intensive Care Units, Neonatal; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics; D017384:Sequence Deletion