Alagille
SyndromeAlagille syndrome is a chromosomal abnormality that occurs with
a frequency of 1 in 100,000 live births. There is a partial or complete deletion of the
jagged-1 gene locus on the 20p.12
chromosome. This results in serious developmental problems of the fetus.
As a result several organ systems are deficient. There is a characteristic facial
appearance and this is associated with abnormalities in the liver, the heart,
the skeleton, the eyes and the kidneys. Signs and symptoms
The babies are first spotted in the newborn nursery when there is a prolonged
neonatal jaundice. A liver biopsy shows absent or too few intrahepatic bile ducts.
Others are diagnosed because of heart disease with right sided heart failure (unusual
otherwise in this age group). If the hepatic duct atresia (missing biliary
ducts) is severe, a liver transplant needs to be made. Here is a list of malformations
associated with Alagille syndrome. Pulmonary stenosis or stenosis
in the pulmonary vessels can lead to right sided heart disease. In addition there
can be other congenital heart defects, such as an atrial septal defect, ventricular
septal defect, patent ductus arteriosus or tetralogy of Fallot. In these cases
the pediatrician would detect certain abnormal heart sounds and heart murmurs.
The kidneys have often cysts or a condition called renal tubular acidosis, where
acids are not adequately eliminated. Bone deformities in the vertebral bodies
are common, which can be seen on X-rays as "butterfly vertebrae". Others
have a shortened ulna or radius or shortened finger bones. There is often a characteristic
finding in the back of the eye that an eye specialist will detect, called “posterior
embryotoxon”. Diagnostic tests Liver, heart and kidney
function have to be determined early in infancy to reduce mortality. Most children
are diagnosed when less than 6 months of age, mostly because of jaundice, otherwise
because of heart problems. A JAG1 defect can be identified by FISH analysis
(“fluorescence in situ hybridization”), which shows the location of the defect
on chromosome 20 (20p.12). Prognosis If serious
heart abnormalities are found, these may have to be attended to by a pediatric
heart surgeon. If serious cholestatic jaundice is due to missing biliary ducts,
an early liver transplant may be required for survival of the child. There is
an overall mortality rate of 10% due to heart, liver or kidney disease. Those
with modestly diminished biliary tract disease in the liver, who do not need a
liver transplant, have a survival rate of 80% over 20 years. Those with more severe
liver disease who did need a liver transplant early in life have a 20 year survival
of about 65%.
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