Review
Unbalanced translocation 6p/16q (partial monosomy 6p and trisomy 16q): prenatal diagnosis and cytogenetics

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Abstract

Unbalanced translocation 6p/16q in one fetus is a very rare event and the prenatal sonographic findings have never been published before. We will give a short overview of the literature along with a case report focussing on prenatal ultrasound features and molecular cytogenetic analysis.

Case description

A 21-year-old primigravid woman presented with a singleton pregnancy at 19 weeks’ gestation. The fetus revealed a mild hydrocephalus, a ventricular septal defect (VSD), a Dandy–Walker malformation as well as an intrauterine growth retardation (IUGR) and limb anomalities. MLPA analysis from amniotic fluid cells showed an unbalanced translocation from the subtelomeric region of chromosome 6p to the subtelomeric region of chromosome 16q. Karyotype of the fetus was 46, XX.ishder(6)t(6;16)(p2?5;q?13)(pVYS246A+, pVYS228B−, pVYS229A+). Despite the karyotype the mother decided not to interrupt pregnancy. The fetus died in utero within the 39th week of gestation and was delivered vaginally after labour induction, with a birth weight of 1815 g.

Prenatal FISH and MLPA studies can be very important to help outline the chromosomal area of deletion and duplication and the sonographic findings forebode the cytogenetic region of interest.

Subsequent to the processing of the case, a complete Medline search was conducted to review previous cases with similar genetic alterations.

Introduction

Partial monosomy 6p in terms of 6p subtelomeric deletion and partial trisomy 16q are at this time two clinically recognizable syndromes that are characterized in the literature very precisely. Over 30 cases of deletion 6p have been reported to date, allowing the definition of a common phenotypic spectrum considering deletions within the terminal 6p24-pter region. Major clinical features associated with terminal deletion include facial dysmorphism (hypertelorism, midface hypoplasia, prominent forehead), malformation of the anterior eye chamber, hearing loss, heart defects and developmental delay [1]. Additionally, individuals with 6p deletion exhibit significant clinical overlap with the Ritscher–Schinzel (craniocerebellocardiac or 3C) syndrome (OMIM #220210) [2] which is very important in prenatal diagnosis. The congruence of major clinical features in chromosome 6p25  pter deletions of cases published so far is outlined in Table 1.

Complete trisomy 16 is the most common autosomal trisomy seen in early spontaneous abortions. It has been rarely observed in later gestation, indicating its incompatibility with life [12], [13]. The first case of partial trisomy 16 for the entire long arm was described in 1975 [14]. Since then, about 30 cases of partial trisomy 16q have been reported. Table 2 clarifies the major clinically and sonographically detectable abnormalities of similar cases published previously. Most of those individuals show limb abnormalities, congenital heart defects and facial characteristics. To our knowledge, only two cases of prenatally diagnosed unbalanced translocation with a partial monosomy 6p and trisomy 16q in one fetus showing sonographical signs of both syndromes mentioned above has been described before [31]. Our focus is on sonographical abnormalities that can be detected prenatally, which was not possible in 1987 when the first two cases were published.

Section snippets

Clinical subject and cytogenetic investigation

A 21-year-old primigravid woman of German descent was referred to our department for extensive sonographic evaluation because of fetal hydrocephalus at 18 + 2 weeks of gestation. The couple was not consanguineous; the father had a history of von Recklinghausen neurofibromatosis. No relative had a history of congenital malformations. Specifically, there was no history of mental retardation, neonatal/infant death, or neurological disorders in their families. The patient denied any exposure to

Discussion

In this special case, MLPA and FISH analysis from amniotic fluid cells revealed a partial monosomy 6p (6p25  pter) and trisomy 16q (16q13 or q21  qter) in one fetus. Conventional chromosomal analysis by G-banding is able to identify numerical and structural chromosomal aberrations, but with this method, unbalanced translocations may be difficult to identify. Under those circumstances, MLPA analysis can rapidly detect the origin of an addendum of some unknown chromosomal segment. The involvement

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  • Cited by (0)

    The research was conducted at the Department of Obstetrics and Gynaecology, University Medicine, Mainz.

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