Delineation of 2q32q35 Deletion Phenotypes: Two Apparent “Proximal” and “Distal” Syndromes

We report on three patients with interstitial deletions of the long arm of chromosome 2 involving bands 2q32.1–q35. They presented with wide-ranging phenotypic variation including facial dysmorphisms, cleft palate, learning difficulties, behavioural issues and severe heart defects. Microarray analysis confirmed an 8.6？Mb deletion in patients 1 and 2 and a 24.7？Mb deletion in patient 3. We discuss the genes involved in the deleted regions including MYO1B, GLS, FRZB, SATB2, and CPS1 and compare the phenotype with those reported in the literature. Taken together, these data suggest that there is a spectrum of disease severity such that patients with deletions encompassing the region of 2q32.1q32.2, which includes the FRZB gene, show an apparently milder phenotype compared to those that lie further distal in 2q32.3q35 that encompasses the SATB2 gene. 1. Introduction Interstitial deletions of the long arm of chromosome 2 involving the 2q31q33 region are responsible for a number of clinical features, including facial dysmorphism, developmental delay, failure to thrive, mental retardation, and behavioural disturbances [1, 2]. There have been approximately 40 patients described in the literature, but a significant number of these cases are not highly resolved, so genotype-phenotype correlations have been difficult to make. More recently, molecular karyotyping has allowed high-resolution characterisation of these deletions. Van Buggenhout et al. [3] have described four independent patients and reported a recognisable pattern of clinical anomalies. Rifai et al. [4] and Cocchella et al. [1] reported two further cases, with the latter refining a critical region for the syndrome and identifying candidate genes to explain the phenotype [5]. The study described here reports on three further cases involving the interstitial region 2q32q35. Patient 1 and her mother, patient 2, carry an 8.6？Mb heterozygous deletion of region 2q32.1q32.3. Patient 3 carries a 24.7？Mb heterozygous deletion involving the region 2q32.2q35. 2. Clinical Report 2.1. Patient 1 The proband (patient 1) was the first child to a nonconsanguineous couple. The antenatal ultrasound scan was normal at 21-week gestation. At 29 + 4 weeks, a clot was seen in the ductus arteriosus, resulting in poor right ventricular function and hydrops fetalis; no structural malformations were observed. An amniocentesis was performed and showed a normal male karyotype. The baby was delivered by emergency caesarean section at 29 + 4 weeks. Despite attempts at resuscitation, the baby died an hour after delivery. Postmortem