An infant was diagnosed with Alagille syndrome (ALGS) due to a de novo NOTCH2 mutation as described in a case report published in the journal Frontiers in Pediatrics.
The case involved a male infant with prenatal oligohydramnios who was born at 35+1 weeks of gestational age via Cesarean section delivery. He had an Apgar score of 10 within the first 10 minutes after birth. His weight was 2000 g, which was small for his gestational age.
The infant’s physicians identified characteristic ALGS facial features, including a broad forehead, a pointed chin, and a nose with a bulbous tip. They also noted that he had very sparse hair and eyebrows.
After birth, the child failed to thrive. He was placed on an amino acid formula, which did not improve his condition. Subsequently, he was placed on a high calorific formula, which did help to improve and normalize his weight. Nevertheless, around 7 months of age, the infant’s appetite and weight gain gradually became poorer.
Read more about Alagille syndrome etiology
In addition, he presented with impaired motor development, for which he was prescribed physiotherapy. Physiotherapy made a clinically meaningful impact; at 9 months of age, he could turn over confidently and sit steadily (but could not climb).
His physicians also noted that he had chronic renal function damage, which was initially discovered 3 days after birth when he had an estimated glomerular filtration rate of 5.2 mL/min/1.73 m2 and elevated serum creatinine levels. In addition, nearly all parameters of his liver function test were abnormal. An abdominal ultrasound revealed bilateral hypodysplastic kidneys.
Genetic testing identified a heterozygous variation in intron 33 of the NOTCH2 gene but no JAG1 genetic variants. The infant’s parents did not carry this mutation, suggesting that it occurred de novo. His physicians later performed a whole exome sequencing for the child.
“In conclusion, Alagille syndrome was diagnosed by considering the results of molecular diagnosis, clinical features, ultrasound, and other auxiliary examinations,” the authors wrote.
Xu F, Peng Q, He X, et al. Alagille syndrome due to a de novo NOTCH2 mutation presenting as prenatal oligohydramnios and congenital bilateral renal hypodysplasia: a case report. Front Pediatr. 2022;10:1020536. doi:10.3389/fped.2022.1020536