Chromosome 2q terminal deletion: Report of 6 new patients and review of phenotype‐breakpoint correlations in 66 individuals

Abstract

We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic-like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling.

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.…”

“…A diagnosis of autism or description of autistic behaviour has been reported in 24-35% of patients. 20,23 Most of the patients in our study had heterogeneous behavioural disorders, with seven in the autistic spectrum, and patients P4 and P11 were reported as being autistic. The 'behaviour' map shows that all affected patients shared a deletion of the following candidate genes: TWIST2, HDAC4, 10 KIF1A, 15 PASK, 5 HDLBP, 5 FARP2, 5 and ATG4B.…”

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…Deletions of chromosome 2q37 are often associated with dysmorphic features, hypotonia, kidney diseases and brachydactyly. 33 Linkage studies have shown suggestive evidence for linkage on chromosome 2q21-q33 differing from the abovementioned cytogenetic findings. The findings of the cytogenetic studies of chromosome 7 deletions, however, overlap with the candidate region derived from genetic linkage studies (see below).…”

Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4

“…To evaluate further diagnostic criteria for the 2q37 deletion syndrome, we compared the clinical findings of our patients and a representative cohort of other published patients carrying HDAC4 mutations or overlapping interstitial or terminal 2q37 deletions ( Figure 3, Table 1). 3,5,[15][16][17][18][19][20][21][22][23][24] The female to male ratio was 21/6. Regarding the body measurements, 4/18 of the patients were microcephalic, 8/24 revealed a short stature and 7/20 an overweight.…”

“…We provide another example that HDAC4 haploinsufficiency is not fully penetrant with regard to the BDE phenotype. 3,16 Furthermore, we assume that it is also the critical genetic mechanism for the BDMR-specific facial pattern besides the BDMR-associated moderate developmental delay and behavioural problems. As patients with 2q37.3 microdeletions including HDAC4 show similar behavioural problems as the ones known for SMS HDAC4 deletions and mutations should be considered in patients with BDMR-specific facial dysmorphism pattern, and a phenotypic spectrum of SMS who are negative for 17p11.2 deletions and mutations of RAI1.…”