Prenatal identification of partial 3q duplication syndrome

Abstract

Background: The 3q duplication syndrome is a result of duplication of a large fragment of the long arm of chromosome 3, mainly 3q21-qter, and in most cases it is diagnosed only after birth. The phenotypic consequences resulting from genetic imbalance are an important source of information for genetic counselling, especially in prenatal diagnostics. However, in most cases it is impossible to define them precisely because the final clinical presentation is a result of an overlap, usually due to different sizes of deletions and/or duplications not only chromosome 3 but also of translocation partner chromosome. In this article, we present a prenatal diagnosis of the 3q duplication syndrome in a foetus, arising from a balanced insertion ins (7,3)(q21.2;q12.3q29) carried by the mother.

Case presentation: The article presents a case of a 29-year-old woman referred to the Genetic Outpatient Clinic for consultation in the 12th week of her fifth pregnancy with a diagnosis of generalised hydrops foetalis. The analysis of karyotype using GTG technique and FISH allowed diagnosis of a balanced aberration in the mother, and determined the type of chromosomal rearrangement, which allowed the identification of the origin of the additional genetic material in the foetus and the previous malformed child of the same couple. The use of molecular karyotyping techniques (FISH and aCGH) allowed a precise determination of the size of the imbalanced fragments in the affected siblings.

Conclusions: The aCGH technique is particularly valuable for the diagnostics of submicroscopic deletions and duplications, if no imbalanced chromosomal aberrations are detected by routine cytogenetic tests. It is also a valuable technique for identifying and fully characterizing genetic material of unknown origin, which can't be identified using routine cytogenetic techniqes. However, it does not allow identification of balanced aberrations in carriers.

Keywords: 3q duplication; Genetic syndrome; Prenatal diagnosis; Ultrasounds.

Fig. 1

Pedigree of the patient with balanced insertion and karyotype: 46, XX, ins (7;3)(q21.2;q12.3q29). White symbol (square or circle) - a healthy person. A symbol (square or circle) with a black dot - a carrier of the balanced insertion ins(7;3). Black symbol (square or circle) - a person with mental retardation (MR) and congenital malformations. Black diamond - an unbalanced structural aberration in the foetus with congenital malformations. n.t. - a person with MR, not tested genetically. Arrow - proband

Fig. 2

Abnormal foetal image in ultrasound examination at 18 weeks of gestation. a - hypoplasia of the cerebellar vermis, absent cavum septum pellucidum, b - cystic hygroma, c - hypertelorism, abnormal nostrils, broad nasal root, d - retrognathia, e - shortening of the long bones, f - clinodactyly of the 5th finger

Fig. 3

a. Karyogram of the foetus (patient III/22) in GTG-banding showing. 46,XX,der(7)ins(7;3)(q21.2;q12.3q29)mat. The arrow indicates abnormal chromosome 7. b. Metaphase spread stained using FISH with a whole-chromosome painting probe for chromosome 7 in fetus III/22. Additional material does not derive from chromosome 7. The arrow indicates abnormal chromosome 7 with additional material of unknown origin. c. Metaphase spread stained by FISH with whole chromosome painting probes: 7 - red, 3 - green in patient III/22. Additional material from chromosome 3 is present on the long arm of chromosome 7. Arrow indicates abnormal chromosome 7 with additional material of chromosome 3

Fig. 4

a. Karyogram of the mother (patient II/11) stained using GTG-banding, showing 46,XX,ins(7;3)(q21.2;q12.3q29). The arrows indicate abnormal chromosomes 3 and 7, with the inserted fragment from chromosome 3. b. Metaphase spread of FISH with whole-chromosome painting probes: 7 - red, 3 - green. Additional material from chromosome 3 is present on the long arm of chromosome 7. The arrow indicates abnormal chromosome 7 with the inserted fragment from chromosome 3