Williams-Beuren syndrome and combined pathology in monochorial twins (literature review and clinical case

Abstract

Summary The widespread introduction of molecular genetic research methods into health care practice has made it possible to diagnose rare microdeletion syndromes in patients with multiple congenital malformations.. Aim of the study is to present the results of a literature search and demonstrate a clinical observation of Williams- Beuren syndrome in 10-month-old monochorionic twins with congenital malformations of the cardiovascular system in combination with kidney pathology and an additional spleen. Results. Williams- Beuren syndrome (WBS) is a rare congenital disorder characterized by specifi c craniofacial dysmorphisms (elphic face) and a hoarse voice in combination with cardiovascular damage, mental retardation, musculoskeletal disorders, and hypercalcemia. WBS occurs in the population with a frequency of 1:7,500-1000 infants. The presence of a specifi c phenotype is associated with a hemizygous microdeletion of the long arm of chromosome 7 at region 7q11.23. The size of the deletion varies from 1.5 to 1.8 Mb and results in the loss of several neighboring genes. The diagnosis is made syndromologically and confi rmed by modern molecular cytogenetic methods. Pathologically signifi cant WBS mutations include loss of the ELN gene and loss of neighboring genes such as LIMK1, RFC2, BAZ1B, GTF2I, STX1A, CLIP2, GTF2IRD, NCF. Haploinsuffi ciency of ELN gene is the main marker of WBS and causes insuffi cient synthesis of elastin protein, which leads to development of pathology of heart and blood vessels (elastin arteriopathy), disorders of connective apparatus of joints, abnormalities of vocal cords and skin. LIMK1 hemizygosity is associated with impaired visual- spatial constructive cognition. Deletion of the RFC2 gene can cause growth retardation and developmental delay. Reduced intelligence can be caused by a mutation of the GTF2I gene and hypercalcemia by a mutation of the BAZ1B gene. The phenotypic manifestations of WBS are also thought to be infl uenced by the reduced expression of fl anking intact genes. The diagnosis, treatment, and adjustment of patients with WBS require an interdisciplinary team of specialists. The presented clinical case demonstrates multisystem pathology in 10-month-old monochorionic dizygotic twins in whom Williams- Beuren syndrome was clinically diagnosed and confi rmed by FISH: ish del (7)(q11.23q11.23)(ELN-). Conclusion. To confi rm the genetic component in congenital multisystem pathology, it is necessary to use modern molecular genetic diagnostic methods. Determination of genetic mutation, its size and origin is important for medical genetic counseling. Early confi rmation of the WBS allows to make an individual prognosis of the child’s life and development, as well as to determine in time the optimal methods of treatment and adaptation, and to advise the parents in planning the next birth of children in the family.