TY - JOUR
T1 - A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease
AU - Miura, Yuichiro
AU - Watanabe, Tatsuya
AU - Uchida, Toshihiko
AU - Nawa, Tatsuro
AU - Endo, Naobumi
AU - Fukuzawa, Taichi
AU - Ohkubo, Ryuji
AU - Takeyama, Junji
AU - Sasaki, Ayako
AU - Hayasaka, Kiyoshi
N1 - Funding Information:
The authors acknowledge Junko Saito, Sachiko Onodera, Yu Aihara (Department of Neonatology, Miyagi Children's Hospital), Jun Murotsuki (Maternal and Fetal Medicine, Miyagi Children's Hospital), Yoshihisa Shimanuki (Radiology, Miyagi Children's Hospital) for their assistance and advice with diagnosis and treatment for the patient.
Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2019/9
Y1 - 2019/9
N2 - Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.
AB - Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979 g, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.
KW - Congenital central hypoventilation syndrome
KW - Extremely low birth weight infant
KW - Non-polyalanine repeat expansion mutation
KW - The paired-like homeobox 2B gene
KW - Variant Hirschsprung's disease
UR - http://www.scopus.com/inward/record.url?scp=85053806588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053806588&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2018.09.008
DO - 10.1016/j.ejmg.2018.09.008
M3 - Article
C2 - 30227298
AN - SCOPUS:85053806588
VL - 62
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 9
M1 - 103541
ER -