Prenatal findings and epimutations for paternal uniparental disomy for chromosome 14 syndrome

Abstract

The phenotypes associated with paternal uniparental disomy for chromosome 14 (UPD(14)pat) are clinically distinctive and caused by genetic alterations at the 14q32.2 imprinted region. Here we describe prenatal and neonatal findings in a case of epimutation associated with UPD(14)pat-like phenotype. A 25-year-old Japanese woman was referred to hospital at 32 weeks of gestation for management of threatened premature delivery. Fetal ultrasound and magnetic resonance imaging showed a narrow thorax and polyhydramnios. At 35 weeks of gestation, emergency cesarean section was performed and placentomegaly was identified. Physical examination of the neonate indicated a small narrow thorax, diastasis recti, and dysmorphic facial features that included hirsute forehead, broad flat nasal bridge, micrognathia, small ears, and a long protruding philtrum. Genetic analysis identified epimutation at the intergenic differentially methylated region (IG-DMR) and at MEG3-DMR.

Pregnancy outcome of autosomal aneuploidies other than common trisomies detected by noninvasive prenatal testing in routine clinical practice

“…So far, there has been no definitive evidence of imprinting diseases related to the region of 7q11.23‐q21.11, 2p25.3‐p11.2, and 2q11.1‐q37.3 observed in 2 of our cases, and the pregnancy outcomes of both cases were normal. Imprinting diseases reported in the literature include transient neonatal diabetes mellitus related to 6q24, Russell‐Silver, Beckwith‐Wiedemann syndrome, Temple syndrome, UPD (14) pat syndrome, Angelman syndrome, Prader‐Willi Syndrome, UPD (20) mat syndrome, pseudohypoparathyoridism type Ib, and others. Thus, genetic counseling should take into account UPD when NIPT shows extra copies for chromosomes involved in well‐known imprinted disease loci, like pat6q24, mat7p11.2‐p12 and q32.2, segmental pat11p15.5, mat/pat14q32, mat/pat15q11‐q13, and UPD (20) mat (several loci involved)/pat20q13.3.…”

Haploinsufficiency of BMP4 and OTX2 in the Foetus with an abnormal facial profile detected in the first trimester of pregnancy

“…Growth restriction, for example, in patients with upd (14) mat [ 11 , 28 ], polyhydramnion in patients with upd (14) pat [ 7 , 29 ] or orofacial malformations in both. Micrognathia, retrognathia or high arch palate are frequently described in patients either with upd (14) mat [ 28 ] or upd (14) pat [ 30 – 32 ]. Paternal isodisomy of chromosome 14 was described in patients with maxillary and mandibular hypoplasia [ 33 ].…”

Kagami-Ogata Syndrome: Case Series and Review of Literature

“…32,33 Three-dimensional ultrasound, fetal X-ray, or fetal magnetic resonance imaging to look for coat-hanger ribs/bell shaped thorax has been used in the past to aid the diagnosis of KOS. [32][33][34] The coat-hanger sign (usually identified on postnatal chest radiographs) could be visible as early as 23 weeks of gestation by prenatal ultrasound. 35 If KOS is suspected in a fetus, parents should be offered amniocentesis for karyotype, CMA, and methylation analysis.…”