Chromosome 2q37 deletion: Clinical and molecular aspects

Abstract

Terminal deletions of chromosome 2 with breakpoints at or within band 2q37, ranging from visible abnormalities to cryptic, subtelomeric deletions, have been recognized with increasing frequency among children with mild-moderate mental retardation, characteristic facial appearance, and behavioral manifestations which often place them on the autism spectrum. The stereotypic facial characteristics include prominent forehead, thin, highly arched eyebrows, depressed nasal bridge, full cheeks, deficient nasal alae and prominent columella, thin upper lip, and various minor anomalies of the pinnae. Abnormal nipples, including inverted nipples, have been reported in a number of cases. CNS, ocular, cardiac, gastrointestinal, renal, and other GU anomalies have been noted in nearly one-third of patients. Of note, coarctation or hypoplasia of the aorta has been described in several affected children. Wilms tumor, renal dysplasia, and tracheomalacia have been reported only with the most proximal breakpoint at band 2q37.1 while a range of GI anomalies, pyloric stenosis, and diaphragmatic defects have been reported with breakpoints throughout the region. A subset of patients with the most distal deletion present phenotypic features which mimic Albright hereditary osteodystrophy (AHO). In addition to the AHO-like phenotype, later onset findings include seizures and cystic kidneys. Timely diagnosis of this recognizable syndrome provides a basis for genetic counseling, appropriate surveillance, and intervention, and avoids unnecessary and expensive diagnostic testing.

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

“…Brachydactyly has been previously described in about half of all patients. 12,20,23 In our series, 10 of 14 patients had brachydactyly type E. The 'skeleton' map ( Figure 4) is consistent with Figure 3 and shows that all patients with brachydactyly had deletions of the same 'skeleton' candidate genes such as PER2, TWIST2, HDAC4, 10 GPC1, 15,16 GPR35, 14 FARP2, STK25 11 and PDC1. HDAC4 remains the major candidate, as reported by Williams et al, 10 but curiously, patients P10 and P13, who did not show brachydactyly, still had deletions of HDAC4.…”

“…Previously reported malformations were rare in this study and might have been coincidental, as they were more frequent when the 2q37 deletion was associated with another chromosomal imbalance (P8, P9, and P14; Tables 1 and 2). The cardiac malformation previously reported in 20% of patients 12 was absent in the 14 patients of our cohort.…”

“…Facial dysmorphism was present in all patients except patient P5, which could be explained by the interstitial deletion ( Figure 1). The characteristic dysmorphic facial features have been previously described in detail (see for review Falk and Casas 12 ) and include the shape of the nose, the appearance of the philtrum, arched eyebrows, a prominent forehead, a small mouth with thin lips and sparse hair. In our cohort, the most frequent features were the V-shaped appearance of the nasal tip, thin arched eyebrows, thin palpebral fissures, a thin upper lip with a smooth philtrum, low set ears, a large chin and hair set low on the forehead.…”

“…In the literature, three genes are associated with this phenotype: HDAC4, 10 CAPN10 12 and HDLBP. 12 Among them, CAPN10 is involved in susceptibility to human noninsulin-dependent diabetes mellitus (MIM 605286) and in increased body weight in mice (Manteia). Nevertheless, the 'overweight' map in Figure 4 shows that these three genes were also deleted in normal-weight patients (P10-12).…”

“…[1][2][3][4][5][6][7][8][9][10] At least 197 genes are located in the 2q37 region (230.7-243.2 Mb; Hg19; NCBI map viewer http://www.ncbi.nlm.nih.gov/mapview/). Of these, 11 have been reported as being potentially related to the 2q37-deletion phenotype so far, 5,[10][11][12][13][14][15][16][17] but the phenotypic implications of most of them remain unknown. Among the candidate genes with a known phenotype, HDAC4 has notably been established as being responsible for brachymetaphalangy and intellectual disability.…”