The Wolf‐Hirschhorn syndrome in fetuses

Abstract

Wolf‐Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft‐lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post‐mortem X‐rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero.

Prenatal Diagnosis of the Wolf-Hirschhorn Syndrome with Increased Nuchal Translucency and Negative Serum Integrated Screening for Trisomy 21

“…7 In severe IUGR, karyotyping can reveal a 4p deletion and in these fetuses the only constant visceral anomaly on autopsy is major renal hypoplasia, as seen in the present case. 8 However, prenatal diagnosis of the 4p deletion can be difficult in the absence of major malformations and only borderline growth restriction with subtle facial anomalies (microretrognathia, short philtrum), as has been reported previously. 9 Moreover, deletions can be missed by traditional cytogenetics.…”

Retinoid Pathway and Congenital Diaphragmatic Hernia: Hypothesis from the Analysis of Chromosomal Abnormalities

“…Several studies have suggested that 15q24-26 and 8p23.1 are critical for normal development of the diaphragm since recurrent deletions within these regions were associated with CDH [33][34][35][39][40][41][42] . CDH has also been reported in several cases of monosomy 4p16pter associated with WolfHirschhorn syndrome [43][44][45] . Other candidate regions such as 1q41-q42, 6p22-p25, or 22q11 have also been described [23,36,38] .…”

Congenital diaphragmatic hernia and a complex heart defect in association with Wolf–Hirschhorn syndrome

“…CDH is a severe birth defect characterized by defective formation of the diaphragm, lung hypoplasia and pulmonary hypertension. This has been previously described in 13 WHS patients [Lazjuk et al, 1980;Tachdjian et al, 1992;Kobori and Gregory, 1993;Bird et al, 1994;Howe et al, 1996;Del Campo and Delicado, 1997;Sergi et al, 1998;Tapper et al, 2002;van Dooren et al, 2004;Pober et al, 2005;Basgul et al, 2006;Casaccia et al, 2006;Battaglia et al, 2008]. Sporadic cases of complex heart defects in association with WHS have been reported [http://www.ncbi.nlm.nih.gov/bookshelf/ br.fcgi?book¼ gene&part¼whs].…”