Prenatal diagnosis of Cri du Chat syndrome: four cases report

Abstract

Cri du Chat syndrome results from a deletion of the short arm of chromosome 5 (5p-). The size of the deletion ranges from the entire short arm to the region 5P 15.3 (5–40 Mb) [1]. The incidence ranges from 1:15,000 to 1:50,000 live-born infants. Hallmark clinical features include a mewing crying, a round face, microcephaly, micrognathia, hypertelorism, epicanthic folds, low-set ears, short stature and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias and cryptorchidism. The majority of the affected cases were found in infancy and childhood. Prenatal diagnosis of the distal 5p deletion is uncommon. The present report describes four prenatal diagnosis cases of Cri du Chat syndrome in association with abnormal ultrasonographic markers. During the past ten years, we had four women with pregnancies confirmed prenatally to have the distal 5p deletion by karyotyping at our center. The indications for invasive testing were summarized in Table I. Antenatal detection can be of benefit with all types of birth defects in giving the couple the option to either terminate the pregnancy or prepare for the delivery of an affected child. Prenatal diagnosis may be offered to pregnant women with a family history of Cri du Chat, but this will identify only a small number of cases that are associated with unequal segregation of a parental translocation. The majority of cases arise de novo, precluding prenatal diagnosis due to family history; therefore, if they are to be identified, it will be only through routine prenatal care. In contrast with the well-established prenatal screening methods for trisomy 21, screening strategies for Cri du Chat are not developed because of its extremely low incidence, although there were occasional reports that prenatal diagnosis was made following abnormal maternal serum biochemical markers [2,3]. Ultrasound scan for fetal anomalies is the most effective screening test, and the majority of reported cases detected in utero were due to abnormal ultrasonographic features [4–10]. As also shown in the current study, three out of four our affected pregnancies were referred for the indication of abnormal ultrasound findings. The remaining one case was identified by chance because of maternal pericentric inversion of chromosome 7. Indeed, a detailed scan at 24 weeks after the availability of karyotype result showed that the fetus had cerebellar hypoplasia, bilateral hydronephrosis and single umbilical artery. Our case report serves as a reminder that it is crucial to carry out a careful scan of basic and extended fetal biometry and structures during second trimester ultrasound examination, as well as soft markers to allow the detection of rarer chromosomal abnormalities.