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 an example of a
child where this was necessary. Here is a list of malformations
associated with Alagille syndrome. Pulmonic 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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