Striking Facial Dysmorphisms and Restricted Thymic Development in a Fetus with a 6-Megabase Deletion of Chromosome 14q

Abstract

During routine ultrasound screening at 12 weeks 5 days of gestation, a nuchal translucency of 7 mm, an omphalocele, and fetal hydrops were found and prompted chorionic villus sampling at 13 weeks 2 days. Chromosome analysis showed an unbalanced karyotype with an abnormal chromosome 14. The mother was a carrier of a translocation karyotype 46,XX,t(13;14) (q34;q32.2). In the fetus this gave rise to a partial trisomy 13q and partial monosomy 14q (fetal karyotype: 46,XX,der[14]t[13;14][q34;q32.2]). By Array-CGH on DNA extracted from a postmortem skin culture, a duplication of approximately 1.7 Mbp of the distal part of chromosome 13q34 and a deletion of approximately 6.0 Mbp of the distal part of chromosome 14q32.2 was demonstrated. Postmortem findings after termination of pregnancy at 14 weeks 6 days included, among others, a severe hypoplasia of the median part of the maxilla, no recognizable nose, a broad median palatoschisis, nonlobulated lungs, a horseshoe kidney with multicystic dysplasia, and decreased development of cortical cellularity in the thymus. These clinical manifestations and autopsy findings of the fetus are compared with those of previously published cases and the possible involvement in this pathology of the YY1 and JAG2 transcription factors and the BCL11b and SIVA-1 regulators of thymic development is discussed.

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

“…Several of these cases have been described in detail. [39][40][41][42][43][44] In addition, we found nine inherited segmental aneuploidies. The 20 de novo aberrations encompassed 125 BAC probes, 14 of which were also identified as single CNCs shared among at least 2 other patients and 5 among the 48 healthy individuals of our study population.…”

Unique Combination of 22q11 and 14qter Microdeletion Syndromes Detected Using Oligonucleotide Array-CGH

“…Some of the clinical findings that can also be attributed to the 14q monosomy are microcephaly, high-arched palate, thin upper lip, carp-shaped mouth, and developmental delay. Anomaly of the aortic arch was also reported in one case of a fetus with a 6 Mb deletion of chromosome 14q [de Pater et al, 2005]. However, most of these symptoms may be seen in both 14q monosomy and 22q11 deletion syndrome, and besides, the patient lacks the most typical symptoms characteristic for 14q terminal deletion syndrome as appointed by Ortigas et al [1997] and summarized by van Karnebeek et al [2002]; this would be, above all, hypotonia, high and prominent forehead, blepharophimosis, and epicanthus.…”

Terminal 14q Deletion and Duplication with Gastrointestinal and Pulmonary Disease

“…Chromosome 14q abnormalities have been associated with various clinical features including inconsistent gastrointestinal and respiratory defects [7][8][9][10][11][12][13][14][15][16][17][18][19]. Phenotypic variability can be attributed to differences in size of the 14q rearrangment, an additional chromosomal abnormality or the parental origin of the additional 14q segment [20][21][22].…”