The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

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.