Ductus Venosus Agenesis as a Marker of Pallister–Killian Syndrome

Abstract

The ductus venosus (DV) is a shunt that allows the direct flow of well-oxygenated blood from the umbilical vein (UV) to the coronary and cerebral circulation through the foramen ovale. Its agenesis has been associated with chromosomal abnormalities and rare genetic syndromes, structural defects, intrauterine growth restriction (IUGR) and even antepartum fetal demise. Pallister–Killian Syndrome (PKS) is a rare sporadic disorder with specific tissue mosaic distribution of an extra 12p isochromosome (i(12p)). Its main clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in literature, prenatal diagnosis is difficult as there are no associated identification signs no distinctive or pathognomonic signs, and some of these malformations are hard to identify prenatally. The tissue mosaicism linked to this syndrome and the decrease of the abnormal clone carrier of the i(p12) after successive trypsinizations of cultured cells makes the diagnosis even more challenging. We present the case of a 27.5 weeks pregnant woman with a fetal ductus venosus agenesis (DVA) as the main guide marker. To our knowledge this is the first case published in literature reporting a DVA as a guide sign to diagnose a complex condition as Pallister–Killian syndrome. We also underscore the key role of new genetic techniques as microarrays to avoid misdiagnosis when only a subtle sonographic sign is present in complex conditions like this.

Diagnóstico Pré-Natal Da Síndrome De Pallister-Killian: Uma Revisão Integrativa

“…Já em um estudo realizado por Alcalde et al 11 mostrou que a presença de uma agenesia do ducto venoso é o resultado de uma falha na formação da anastomose crítica entre o sistema venoso portal-umbilical e o sistema venoso hepático-sistêmico. Por isso, esse achado deve ser complementado com estudo detalhado da anatomia fetal, uma vez que a associação com malformações cardíacas e extracardíacas é descrita em mais de 80% dos casos, incluindo defeitos septais, cardiomiopatia hipertrófica, fissuras faciais, má rotação intestinal e outras anomalias do sistema venoso.…”

“…Alcalde et al 11 Relato de caso de diagnóstico pré-natal da Sindrome de Pallister-Killian com agenesia do ducto venoso como principal sinal guia ultrassonográfico.…”

A large-scale investigation by ultrasound of fetal hepatic venous system variants in China

“…Early in the embryonic development, two UVs and two vitelline veins (VVs) supply blood to the fetal liver, and the subsequent development of UVs and VVs follow a set of biological procedures [5][6][7]. The entire right UV and the cranial portion of the left UV (LUV) regress and the caudal portion of LUV contributes to the left PV (LPV).…”

Pallister–Killian Syndrome versus Trisomy 12p—A Clinical Study of 5 New Cases and a Literature Review

“…Typical facial characteristics include frontal bossing and high frontal hairline, temporofrontal balding, sparse eyebrows and lashes, hypertelorism, small and flat nose, full cheeks, long and simple philtrum, large mouth with downturned corners, thin upper lip and distinct cupid bow ("Pallister lip"), micrognathia, and low-set dysplastic ears [21][22][23][24][25][26][27][28][29][30]. Orodental features also include macroglossia, alveolar ridge or gingival overgrowth, delayed teeth eruption, and missing or double teeth [28].…”

“…Prenatal sonographic features suggestive for PKS include polyhydramnios, increased nuchal translucency, extremely flat facial profile, congenital diaphragmatic hernia, small stomach, as well as short limbs with small or abnormal extremities [11]. Ductus venosus agenesis might be a prenatal marker, however as it is associated with many complex syndromes, only its association with polyhydramnios, fetal macrosomia, and eventually short femoral bone or other minor defects should alert for PKS [30,38]. Array CGH on genomic DNA extraction from uncultured amniocytes may help to obtain a final diagnosis.…”