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This autosomal dominant association involves primarily the heart (ventricular septal defect, atrial septal defect), pulmonary artery stenoses, and hepatic dysfunction. Coagulation disorders can be important. The presence of a broad forehead and long, thin face are characteristic.

Cardiovertebral Syndrome; Alagille-Watson Syndrome; Watson-Miller Syndrome; Arteriohepatic Dysplasia (AHD); Cholestasis-Peripheral Pulmonary Stenosis; Hepatic Ductular Hypoplasia-Multiple Malformations Syndrome; Hepatofacioneuro-Cardiovertebral Syndrome.

1:100,000 live births.

Autosomal dominant with highly variable expression. However, 15 to 50% of cases are new mutations. The defect has been assigned to chromosome 20 band p12.


Based on the clinical findings, although there is wide variability in the manifestations of the disease. Diagnostic criteria require the presence of cholestasis and two of the following findings: characteristic facies, pulmonary artery stenosis, “butterfly” hemivertebrae, and posterior embryotoxon (thickening of Descemet membrane and corneal endothelium).

Presentation of Alagille syndrome is highly variable with respect to all the organ systems involved but consists mainly of prolonged neonatal jaundice or cardiac symptoms/signs. However, patients may be asymptomatic, or the jaundice may resolve by age 2 years. The spectrum of hepatic disease is highly variable. Pruritus may be the main symptom and often is invalidating. Liver biopsy reveals a paucity of intrahepatic bile ducts. Other features are hepatomegaly, obstructive liver disease, cirrhosis, splenomegaly, and truncal and facial telangiectasia. Deficiencies of fat-soluble vitamins are frequent and may result in coagulopathy (vitamin K), rickets (vitamin D), retinopathy (vitamin A, E), peripheral neuropathy, and myopathy (vitamin E). Liver function tests show elevated serum bile acid concentrations, conjugated hyperbilirubinemia, and elevated serum levels of alkaline phosphatase and γ-glutamyl transferase. The characteristic features of “cholestasis facies” are a round face with prominent ears, bulbous nose, and pointed chin. A prominent forehead, deeply set eyes, hypertelorism, straight nose, short philtrum, down-slanted palpebral fissures, micrognathia/retrognathia, and brachycephaly may occur. Cardiovascular anomalies are present in 95% of patients and may include peripheral pulmonic stenosis, systemic hypertension, atrial septal defect, ventricular septal defect, coarctation of the aorta, and tetralogy of Fallot. Musculoskeletal features involve the vertebrae (“butterfly” hemivertebrae denotes vertebrae, which are split sagittally into pairs because of failure of fusion of their anterior arches). Abnormal ribs, spina bifida occulta, delayed bone age, absent or abnormal ulnae, terminal hypoplasia of the fingers, and clinodactyly of the fifth finger may be seen. In association with posterior embryotoxon other ophthalmologic features can occur, such as strabismus secondary to paresis of ocular muscles, keratoconus (and other structural abnormalities of the cornea), eccentric or ectopic pupils, enophthalmos, and pigmentary retinopathy. Cerebrovascular complications may include MoyaMoya Disease (progressive obliteration of the intracranial carotid arteries and formation of an extensive vascular network of dilated small branches). Other signs are regrouped as minor signs and include undescended/ectopic testes, ureteral anomalies, renal agenesis/hypoplasia/dysplasia, renal artery stenosis, intrauterine growth retardation, late puberty, hypogonadism, and mental retardation. Hepatocellular carcinoma and papillary thyroid carcinoma may occur as a late complication.

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