Three new cases of terminal deletion of the long arm of chromosome 7 and literature review to correlate genotype and phenotype manifestations

Abstract

Partial monosomy of the long arm of chromosome 7 has been characterized by wide phenotypic manifestations, but holoprosencephaly (HPE) and sacral agenesis have frequently been associated with this chromosomal deletion. A clear relationship between genotype and phenotype remains to be defined in the 7q deletion syndrome. Three patients (1, 2, and 3) were investigated with 7q terminal deletion and compared with similar deletion cases in the literature in order to stratify the phenotypes associated with 7q35 and 7q36 terminal deletion patients. Patients 1, 2, and 3 were carrying a de novo terminal deletion at bands 7q36.2, 7q35, and 7q36.1, respectively. In patient 3, a small Xq28 duplication was also identified by array-CGH. Our patients presented with heterogeneous phenotypic manifestations, which could imply the possible role of environmental factors (multifactorial inheritance), structural variations in the non-coding regions, penetrance, and/or polymorphism. The varying length of deletion was also taken into account. Growth retardation was the most frequent symptom found in both 7q35 and 7q36 patients we reviewed. The occurrence of HPE and sacral malformation together was seen in less than 10% of the reviewed cases in both kinds of deletion. HPE was associated mainly in cases with an unbalanced translocation.

7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case

“…This is in agreement with the observation that severe forms of HPE are more frequently found in terminal 7q deletion patients associated with another partial trisomy than in those with pure 7q deletion [Lukusa et al, 2005]. Although the most severe forms of HPE cases involve 7q deletion and 3p duplication [Chen et al, 1999], others are accompanied by 2q, 2p, 8p, 18q, 1q, and 22q duplication [reviewed in Ayub et al, 2016]. There are at least 3 exceptional cases of patients without HPE, despite being carriers of a 7q deletion and other chromosome duplications [Kuller et al, 1992;Ginocchio et al, 2008;Ayub et al, 2016].…”

“…Although the most severe forms of HPE cases involve 7q deletion and 3p duplication [Chen et al, 1999], others are accompanied by 2q, 2p, 8p, 18q, 1q, and 22q duplication [reviewed in Ayub et al, 2016]. There are at least 3 exceptional cases of patients without HPE, despite being carriers of a 7q deletion and other chromosome duplications [Kuller et al, 1992;Ginocchio et al, 2008;Ayub et al, 2016]. This could be explained by the fact that none of the genes involved in brain development are present in the duplicated region.…”

“…It is assumed that when a 7q deletion is accompanied by partial trisomy of another chromosome, the result is a more severe cerebral phenotype, due to extra gene dosage [Ayub et al, 2016]. Furthermore, there are 4 genes ( RE-PIN1 or AP4 , CDK5 , DPP6 , and EN2 ) at the deleted and 1 gene ( ANKLE2 ) at the duplicated region, which may play a role in brain development.…”

Kaposi sarcoma, oral malformations, mitral dysplasia, and scoliosis associated with 7q34‐q36.3 heterozygous terminal deletion

“…To date, there are 23 reported cases of isolated heterozygous chromosome 7q terminal deletion (Table I) between 7q32 and 7q36.3 [Ayub et al, 2016; Beleza-Meireles et al, 2013; Benzacken et al, 1997; Frints et al, 1998; Horn et al, 2004; Masuno et al, 1990; Rodriguez et al, 2002; Roessler et al, 1997; Su et al, 2008]. All except two patients had microcephaly and/or holoprosencephaly (HPE).…”

An Interstitial Deletion at 7q33-36.1 in a Patient with Intellectual Disability, Significant Language Delay, and Severe Microcephaly

“…Terminal deletions at the long arm of chromosome 7 have been described more frequently in the medical literature [1, 2] compared to interstitial deletions at the distal 7q region. Patients with terminal deletions often have severe phenotypic features including sacral agenesis and holoprosencephaly [2, 3], whereas, the above mentioned interstitial deletions have characteristic dysmorphic facial features, intellectual disability, and language impairment which will be further described in this report.…”