Isolated hemihyperplasia (hemihypertrophy): Report of a prospective multicenter study of the incidence of neoplasia and review

Abstract

Hemihyperplasia is characterized by asymmetric growth of cranium, face, trunk, limbs, and/or digits, with or without visceral involvement. It may be an isolated finding in an otherwise normal individual, or it may occur in several syndromes. Although isolated hemihyperplasia (IHH) is of unknown cause, it may represent one end of the clinical spectrum of the Wiedemann-Beckwith syndrome (WBS). Uniparental paternal disomy of 11p15.5 or altered expression of insulin-like growth factor 2 (IGF2) from the normally silent maternal allele have been implicated as causes of some cases of WBS. IHH and other mild manifestations of WBS may represent patchy overexpression of the IGF2 gene following defective imprinting in a mosaic fashion. The natural history of IHH varies markedly. An association among many overgrowth syndromes and a predisposition to neoplasia is well recognized. Heretofore the risk for tumor development in children with IHH was unknown. We report on the results of a prospective multicenter clinical study of the incidence and nature of neoplasia in children evaluated because of IHH. One hundred sixty-eight patients were ascertained. A total of 10 tumors developed in nine patients, for an overall incidence of 5.9%. Tumors were of embryonal origin (similar to those noted in other overgrowth disorders), including Wilms tumor, hepatoblastoma, adrenal cell carcinoma, and leiomyosarcoma of the small bowel in one case. These data support a tumor surveillance protocol for children with IHH similar to that performed in other syndromes associated with overgrowth.

Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith–Wiedemann syndrome

“…Clinically, it has to be distinguished from other overgrowth syndromes (OGS) such as Simpson ± Golabi ± Behmel syndrome and it must also be recognised in its incomplete or related forms such as nonsyndromic IGF2 overgrowth disorder 4 and isolated hemihyperplasia. 5 Molecular diagnosis is also difficult, mostly because of the large spectrum of genetic and epigenetic abnormalities. Current molecular tests allow diagnosis of BWS in only one third of patients: rare patients with cytogenetic abnormalities, 20% of patients with 11p15 UPD, 8% of patients with hypermethylation of the H19 gene and 5% of patients with a mutation in CDKN1C.…”

Isolated Hemihypertrophy (Hemihyperplasia): A case report and review of the literature

“…İHH'li çocuklarda ortalama yaşam süresi beklenebilmekle birlikte eşlik eden anomaliler uzun dönem prognozunu değiş-tirebilmektedir. 4 Sıklıkla sporadik olarak görülse de ailesel geçiş de tanımlanmıştır. 2 Olgumuzun aile öyküsünde benzer sendromların olmaması ve diğer eşlik eden bulguların yokluğu nedeniyle hastamız sporadik, izole basit hemihipertrofi olarak değerlendirildi.…”

Hemihypertrophy Spectrum

“…The asymmetry can be due to differences in the growth of soft tissue, bone, or both [2] Hemihyperplasia may be an isolated finding, or it may be part of multiple malformation syndromes, such as Russell-Silver syndrome, Proteus syndrome, Beckwith-Wiedemann Syndrome (BWS), and Sotos syndrome [3,4]. Isolated hemihyperplasia (IH, OMIM 235000) is defined as asymmetric regional body overgrowth due to an underlying abnormality of cell proliferation without any other underlying diagnosis [5]. Rowe [6] proposed a classification system for hemihyperplasia, based on anatomic site of involvement.…”

“…The etiology of IH is unknown. A number of different chromosomal anomalies, including trisomy [7] mosaicism and diploidtriploid mosaicism, have been identified, and the causes of IH are likely to be heterogeneous [5]. It has been suggested that IH could be one end of the spectrum of phenotypes of BWS [8], linked to the chromosomal locus 11p15 [9].…”