Hardikar Syndrome

Clinical Features

Hardikar et al. (1992) reported 2 unrelated girls with obstructive hepatic cholestasis and cholangitis associated with cleft lip/palate, hydronephrosis/hydroureter, retinal pigmentation, and intestinal septum. The features were apparent at birth. Both patients had recurrent urinary tract infections, early onset of jaundice, and poor weight gain. Both also developed hepatomegaly and pruritus. Nydegger et al. (2008) reported long-term follow-up of the patients reported by Hardikar et al. (1992). The first patient had cleft lip and palate, pigmentary retinopathy, aortic coarctation, vesicoureteric reflux, obstructive liver disease, and malrotation of the gut. Liver biopsy showed ductal proliferation with hepatic artery hypertrophy. She developed recurrent obstructive jaundice that required surgical intervention at age 13 years. The second patient was born by artificial insemination by donor sperm. She had cleft soft palate, pigmentary retinopathy, hydroureters with distal obstruction, jejunal septum, patent foramen ovale, and mild pulmonary artery stenosis. Liver biopsy showed multiple cystic dilations of the intrahepatic ducts and stenosis of the common bile duct. She required liver transplantation at age 15 years. Cognition in both patients was normal. Hardikar et al. (1992) commented on the multiple tubular stenoses apparent in these patients. Nydegger et al. (2008) noted that the syndrome resembled the Kabuki (147920) and Alagille (ALGS1; 118450) syndromes.

Cools and Jaeken (1997) reported an infant girl with Hardikar syndrome. She had cleft lip and palate, pigmentary retinopathy, hydroureteronephrosis with severe vesicoureteral reflux, cholestasis, and nonrotation of the gut. Liver ultrasound showed dilated intrahepatic bile ducts, and biopsy showed fibrosis with ductal proliferation and inflammatory cells. She also had patent ductus arteriosus and a small ventricular septal defect. Dysmorphic facial features included long narrow palpebral fissures, depressed nasal tip, and preauricular dimples. She was noted to have moderate psychomotor delay at that time, but follow-up by Nydegger et al. (2008) reported normal development at age 11 years. Cools and Jaeken (1997) had noted that the syndrome resembled the Kabuki syndrome.

Maluf et al. (2002) reported a girl with features consistent with Hardikar syndrome. She had cleft lip and palate, retinopathy, intestinal malrotation, and recurrent urinary tract infections associated with stenosis of the ureters. She was jaundiced from birth. Liver biopsy showed cirrhosis with regenerating nodules, portal chronic inflammation with bile duct proliferation, and lobular cholestasis. The liver disease was progressive, requiring transplantation at age 24 months. Nydegger et al. (2008) provided follow-up on the girl and noted that she had an excellent clinical course after transplantation and had normal development at age 8 years.

Poley and Proud (2008) reported another girl with Hardikar syndrome who had malrotation of the gut, pigmentary retinopathy, patent ductus arteriosus, hydronephrosis, and persistent cholestasis resulting in liver failure and transplant. Additional features included vaginal atresia and a common urogenital sinus. Mild dysmorphic facial features were also noted: a prominent forehead, hypertelorism, small chin, bulbous nose, and preauricular dimples. Poley and Proud (2008) postulated that the constellation of defects correlated with a critical time of organogenesis between 30 and 70 days' gestation.