Prenatal diagnosis of Pallister–Killian syndrome

Abstract

Pallister–Killian syndrome (PKS) was first described by Pallister et al. in 19771. This syndrome is the result of partial tetrasomy of the short arm of chromosome 12, but the mechanism that leads to the formation of isochromosome 12p in PKS is not clear, though it is thought to be related to parental, particularly maternal, age2,3. Prenatal diagnosis of PKS is usually incidental on karyotyping in cases of advanced maternal age, increased nuchal translucency thickness or a fetal anomaly detected on ultrasound4. We report a case of PKS suspected on prenatal ultrasound examination, which presented with cystic fibrosis. A 34-year-old woman, para 3, had prenatal care at a specialized ultrasonography clinic in Goiânia, Brazil after initial prenatal care in Barreiras, Brazil showed fetal hydrocephalus. She and her husband, who was 56, were healthy at the time of the appointment and were non-consanguineous, with no family history of congenital malformations. The mother had been treated for epilepsy in childhood and two previous pregnancies ended in miscarriage. Serial ultrasound examinations showed hydrocephalus with the lateral ventricles measuring 16.9 mm (Figure 1), hypoplasia of the nasal bone, nuchal fold of 7.5 mm, atrophic gut and hypotrophic genitalia. Ultrasound-guided amniocentesis and karyotyping at 23 weeks of gestation revealed male fetal sex and the presence of cells with the additional isochromosome (karyotype, 47,XY,+i(12p)(?)), prompting a diagnosis of PKS. Physical examination of the term neonate revealed a webbed neck, low-set ears, frontal bossing, disproportionately sized hands and feet for body size, ambiguous genitalia and suspected hydrocephalus (Figure 2). Serial chest X-rays detected persistent pneumonia and cardiomegaly, while laboratory tests showed late sepsis and cystic fibrosis. The neonate survived 41 days postpartum. One variation in this case from those in the literature is the presence of cystic fibrosis, which significantly complicated the neonate's clinical condition and compromised his life expectancy. We believe this is the first report of cystic fibrosis associated with PKS. On the day prior to demise, the neonate had a non-specific allergic reaction with a cutaneous rash on the lower limbs that improved with corticosteroid treatment, as well as a coagulation disorder with profuse bleeding at the puncture points for central access and gasometry. The cause of these clinical intercurrences was not identified in the patient's medical records and no association of these findings with PKS was found in the medical literature3. Ultrasound and karyotyping made it possible to diagnose PKS prenatally, prepare adequately for delivery and guide genetic counseling. There is no specific therapy for PKS, but affected children can improve clinically with early intervention and special education programs. Further clinical research is needed to investigate if the presence of cystic fibrosis is an integrating and complicating part of the syndrome or whether this finding was merely sporadic. This case emphasizes the importance of routine ultrasonographic practice in prenatal care as a method of early detection of fetal malformations, making possible genetic study which constitutes the gold standard for diagnosis of PKS as well as the determination of prognosis.