Elsevier

European Journal of Medical Genetics

Volume 50, Issue 6, November–December 2007, Pages 475-481
European Journal of Medical Genetics

Short report
Prenatal diagnosis of mosaicism for 11q terminal deletion

https://doi.org/10.1016/j.ejmg.2007.06.002Get rights and content

Abstract

The phenotype of 11q terminal deletion also known as Jacobsen syndrome is a clinically well known entity whose diagnosis in infancy and childhood is based on clinical examination, hematological and cytogenetic findings. Hematological features in Jacobsen syndrome are very similar to those reported in Paris–Trousseau syndrome (PTS) which is also associated with11q terminal deletion. Karyotype analysis shows a variable terminal deletion from 11q23 sub-band extending to the telomere. Most often in patients with Jacobsen syndrome, this chromosomal deletion is present in all metaphases. We report on the identification of a distal 11q deletion in mosaic (20% of deleted cells) in a fetus ascertained after amniocentesis for maternal serum screening test indicative for Down syndrome. The present case is the third prenatal diagnosis of a mosaic for a distal 11q deletion with the lowest mosaicism rate. The 2D-ultrasound examination and cord blood hematological studies were useful to estimate the prognosis at term, considering the contribution of the mosaicism rate to the phenotypic variability in Jacobsen syndrome. The identification of mosaicism for distal 11q deletion is a very rare event in prenatal diagnosis. This case illustrates the complexity in genetic counselling for prenatally ascertained partial monosomy 11qter in mosaic.

Introduction

Jacobsen syndrome, or distal deletion of the long arm of chromosome 11 (OMIM#147791), is a rare but clinically well known entity [9], [11], [20] and has an incidence of approximately 1 in 100 000 births. Patients usually have visible deletions based on karyotype analysis: the breakpoint arises typically in 11q23.3 sub-band but can be located in 11q24 or 11q25 with deletions extending to the telomere [15]. Most frequently (85%), this deletion appears de novo. Other cases are the result of malsegregation from balanced parental rearrangements; in some patients Jacobsen syndrome is associated with a de novo chromosomal event as ring chromosome 11 [6]. There is a broad clinical spectrum of Jacobsen syndrome. Clinical manifestations can include developmental delay, psychomotor retardation, short stature, craniofacial features (trigonocephaly, hypertelorism, broad and flat nasal bridge, carp-shaped mouth with thin upper lip, low-set malformed ears), congenital heart defects (hypoplastic left heart syndrome, membranous ventricular septal defect, aortic arch defects), genitourinary anomalies, pyloric stenosis, ocular malformations (ptosis, colobomas, cataracts, glaucoma, strabismus, telecanthus), limb anomalies (talipes equinovarus, clino- or camptodactyly, syndactyly), recurrent infectious episodes and thrombocytopenia or pancytopenia. Hematological features in PTS include thrombocytopenia with or without pancytopenia and platelet abnormalities [2], [7]. Favier et al. [8] noted clinical, hematological and cytogenetic similarities between Jacobsen syndrome and PTS. They concluded that there is clearly a clinical overlap between these two syndromes, which are both associated with 11q terminal deletion. In the PTS, hemizygous deletion of the monoallelic expressed FLI1 gene contributes to the hematopoietic defects. The majority of Jacobsen syndrome affected cases were reported in infancy and childhood, however 14 affected fetuses were described with different pregnancy outcomes [4]. Only two cases of prenatally diagnosed 11q terminal deletion mosaicism are described in the literature [3], [16]. In the present study, we report on a fetus with 11q terminal deletion mosaicism. The fetus presented with minor clinical features of Jacobsen syndrome after second trimester ultrasound examination but very suggestive hematological anomalies on cord blood.

Section snippets

Case report

A 37-year-old primigravid woman underwent amniocentesis at 21 weeks' gestation because of a serum screening test positive for Down syndrome (1/78 for a normal test at 1/250) without ultrasound anomalies at the first examination. At 14.4 weeks' gestation, the maternal blood screening test showed a serum alpha-fetoprotein level of 0.66 multiples of the median (MoM) and a serum β-human chorionic gonadotrophin level of 1.52 MoM. Amniocentesis was performed at 21 weeks' gestation for foetal karyotype

Results

The first amniocentesis allowed the characterization of a mosaic karyotype: 46,XY[16]/46,XY,del(11)(q23)[3]. A second amniocentesis was realized at 24 week's gestation: 7 out of 36 colonies showed the same 11q terminal deletion extending from the 11q23 sub-band to the telomere (Fig. 1A). Fluorescence in situ hybridization (FISH) studies with 11q subtelomeric probe (Fig. 1B) but also with a probe specific for the FLI1 gene (RP11-138K22; Fig. 1C) confirmed the mosaic deletion with a mosaicism rate

Discussion

Jacobsen syndrome is a well known contiguous gene syndrome resulting from 11q23.3-qter deletion. The human reference genome at the National Center for Biotechnology Information (NCBI build 36.2) (http://www.ncbi.nlm.nih.gov) reports the localization of a total of 248 genes in this chromosomal region. Clinical signs of Jacobsen syndrome can include Paris–Trousseau type of thrombocytopenia if the deletion extends to 11q23. If the diagnosis of Jacobsen syndrome is easily established in infancy and

References (20)

  • J. Breton-Gorius et al.

    A new congenital dysmegakaryopoietic thrombocytopenia (Paris–Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23

    Blood

    (1995)
  • D. Boehm et al.

    Prenatal diagnosis of a large de novo terminal deletion of chromosome 11q

    Prenat. Diagn

    (2006)
  • T.H. Bui et al.

    European collaborative study on prenatal diagnosis: mosaicism, pseudomosaicism and single abnormal cells in amniotic fluid cell cultures

    Prenat. Diagn

    (1984)
  • C.P. Chen et al.

    Prenatal diagnosis of the distal 11q deletion and review of the literature

    Prenat. Diagn

    (2004)
  • C.P. Chen et al.

    Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts

    Prenat. Diagn

    (2001)
  • A. Donnenfeld et al.

    Chromosome 11, monosomy 11q

  • R. Favier et al.

    A novel genetic thrombocytopenia (Paris–Trousseau) associated with platelet inclusions, dysmegakaryopoiesis and chromosome deletion AT 11q23

    C R, Acad. Sci. III

    (1993)
  • R. Favier et al.

    Paris–Trousseau syndrome: clinical, hematological, molecular data of ten new cases

    Thromb. Haemost

    (2003)
  • J.P. Fryns et al.

    Distal 11q monosomy. The typical 11q monosomy syndrome is due to deletion of subband 11q24.1

    Clin. Genet.

    (1986)
  • P.D. Grossfeld et al.

    The 11q terminal deletion disorder: a prospective study of 110 cases

    Am. J. Med. Genet. A

    (2004)
There are more references available in the full text version of this article.

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