Congenital portosystemic shunt in a child with Wolf–Hirschhorn syndrome

Congenital portosystemic shunt (PSS) is an uncommon vascular anomaly caused by abnormal development of the vitelloumbilical venous plexus during embryogenesis [Hofstaetter et al., 2000]. PSS is rarely associated with chromosomal aberrations, such as Down syndrome and Turner syndrome [Kieran et al., 1992; Kitagawa et al., 1992; Courtens et al., 2000; Pipitone et al., 2003; Saxena et al., 2004; Noe et al., 2006; Morotti et al., 2007]. Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is well known to involve multiple congenital anomalies caused by partial loss of the short arm of chromosome 4 (4p16.3) [Battaglia et al., 2001]. To our knowledge, however, PSS has not been reported in WHS. We report on the first case of congenital PSS in a patient with WHS. A small-for-gestational-age male infant was born at 38 weeks’ gestation. The birth weight was 1,808 g, the body length was 42.5 cm, and the head circumference was 29.9 cm. The Apgar scores were 9 and 9 at 1 and 5 min, respectively. This boy’s parents (mother: 29 years, father: 32 years) were nonconsanguineous and healthy. He was delivered after the mother’s first pregnancy. He presented with a typical ‘‘Greek helmet’’ appearance of the face, hypospadias, and hypotonia. Neonatal seizures, which were well controlled by monotherapy with phenobarbital, and meconium plug syndrome developed. WHS was diagnosed on the basis of the characteristic clinical features and the results of chromosomal analysis, showing 46,XY,add(4)(p15.2). A GTG-banded chromosomal analysis and fluorescence in situ hybridization (FISH) analyses (spectral karyotyping and subtelomeric analyses) could not identify the source of this abnormality (Fig. 1). Chromosomal analyses of both parents were normal. Screening for galactosemia at 5 days of age revealed a mildly elevated blood galactose level of 0.75 mmol/L (normal <0.33 mmol/L). Repeated tests consistently showed increased blood galactose levels (0.6–1.1 mmol/L). Activities of all three major galactose metabolic enzymes (galactose-1-phosphate uridyl transferase, galactokinase, and uridine diphosphate galactose epimerase) were normal. The arterial blood ammonia level was 77 mmol/L (normal 10–40 mmol/L), and the serum total bile acid level was 87 mmol/L (normal <10 mmol/L). Ultrasonography showed no evidence of a PSS. However, contrast-enhanced computed tomography (CT) disclosed a large communication between the portal vein and the left renal vein draining into the inferior vena cava. The classic features of WHS include a ‘‘Greek warrior helmet’’ facial profile, neurodevelopmental delay, growth retardation, and seizures [Zollino et al., 2008]. The incidence of WHS at birth is about 1 per 100,000 newborns [Shannon et al., 2001]. The severity of the WHS phenotype is generally related to the extent of the 4p deletion, categorized into three groups: a mild phenotype with a small deletion not exceeding 3.5 Mb, a widely recognizable WHS phenotype with a large deletion between 5 and 18 Mb, and a severe phenotype with a very large deletion exceeding 22 Mb [Zollino et al., 2008]. Our patient had a large chromosomal deletion of the 4p terminal, which extended 27.9 Mb, leading to a severe phenotype of WHS. The origin of additional chromosome remains unknown. Congenital PSSs were rarely identified in early infancy previously [Guariso et al., 1998], but currently can be diagnosed early in life by mass screening for galactosemia and advanced diagnostic