Inspired by a patient
Ayub S, Gadji M, Krabchi K, Côté S, Gekas J, Maranda B, Drouin R. Three new cases of terminal deletion of the long arm of chromosome 7 and literature review to correlate genotype and phenotype manifestations. Am J Med Genet A. 2016 Apr;170A(4):896-907.
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.
Cococcioni L, Paccagnini S, Pozzi E, Spaccini L, Cattaneo E, Redaelli S, Crosti F, Zuccotti GV. Currarino syndrome and microcephaly due to a rare 7q36.2 microdeletion: a case report. Ital J Pediatr. 2018 May 25;44(1):59.
Currarino syndrome is a rare condition characterized by presacral mass, anorectal malformation and sacral dysgenesis.
We report the case of a child that presented chronic constipation, encopresis and mycrocephaly. The characteristics were initially compatible with a case of functional constipation and a therapy with polyethylene glycol was prescribed. After a year, because of poor response, a plain abdominal X-ray was performed, detecting sacrum abnormalities. Finally, a CGH-array analysis was performed and a form of Currarino Syndrome caused by a rare 7q36 microdeletion, was diagnosed.
Occult spinal dysraphism should be suspected in case of poor polyethylene glycol responder constipation, even when evident sacral abnormalities on the physical examination are not detected.
Suri T, Dixit A. The phenotype of EZH2 haploinsufficiency-1.2-Mb deletion at 7q36.1 in a child with tall stature and intellectual disability. Am J Med Genet A 2017 Oct;173(10):2731-2735.
Weaver syndrome is a rare overgrowth syndrome with distinct facial features in young children and variable learning disability. Heterozygous missense mutations in EZH2 are present in over 90% of patients with Weaver syndrome but the exact mechanism by which EZH2 mutations cause Weaver syndrome is unknown. We report an 11-year-old boy with a de novo 1.2-Mb deletion at 7q36.1 including EZH2 who has tall stature, significant intellectual disability, and some physical features of Weaver syndrome. Emerging evidence in the literature indicates that Weaver syndrome EZH2 mutations may result in loss of function of the gene and our report suggests that haploinsufficiency of EZH2 may replicate the clinical phenotype of Weaver syndrome.