Prenatal Diagnosis of a Mosaic Paternal Uniparental Disomy for Chromosome 14: A Case Report of Kagami–Ogata Syndrome

The Kagami–Ogata syndrome (KOS) is a rare imprinting disorder with a distinct clinical phenotype. In KOS, polyhydramnios is associated with a small bell-shaped thorax and coat-hanger ribs. The genetic etiology of KOS includes paternal uniparental disomy 14 [upd(14)pat], epimutations, and microdeletions affecting the maternally derived imprinted region of chromosome 14q32.2. More than 77 cases of KOS have been reported; however, only one mosaic upd(14)pat case has been reported. Here we report a second mosaic upd(14)pat case. The prognosis of upd(14)pat patients is poor because of severe respiratory insufficiency. We summarized prenatal ultrasound findings of KOS to raise awareness of this condition for possible diagnosis of KOS prenatally when polyhydramnios combination with a small bell-shaped thorax and other related features are first observed. Prenatal diagnosis using methylation-specific multiplex ligation-dependent probe amplification (MLPA) or a single-nucleotide polymorphism-based microarray analysis is recommended.

Paternal Uniparental Disomy of Chromosome 14 with Hypospadias

Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (‘coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.