Postnatally confirmed COL4A1 mutation in a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia
10.3760/cma.j.cn113903-20211215-01036
- VernacularTitle:胎儿反复脑实质出血及囊性脑白质软化灶形成生后确诊为 COL4A1基因突变1例
- Author:
Qianqi LIU
1
;
Ying ZHU
;
Xinlin HOU
;
Weijie SUN
;
Junya CHEN
Author Information
1. 北京大学第一医院妇产科，北京 100034
- Keywords:
Cerebral hemorrhage;
Leukomalacia, periventricular;
Collagen type Ⅳ;
Mutation;
Ultrasonography, prenatal;
Fetus
- From:
Chinese Journal of Perinatal Medicine
2022;25(10):793-796
- CountryChina
- Language:Chinese
-
Abstract:
We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.
