Sporadic COL4A1 mutations with extensive prenatal porencephaly resembling hydranencephaly

COL4A1 mutations were initially described in familial porencephaly (OMIM 175780).1,–,3 The phenotypic spectrum of COL4A1 mutations is, however, wide and includes cerebral white matter small vessel disease, cerebral aneurysms, cataract, anterior segment dysgenesis, microcornea, nephropathy, muscle cramps, and cardiac arrhythmia.4,–,6 Prenatal onset has been documented.7 Phenotype–genotype correlation has been proposed for the HANAC phenotype (OMIM 611773).5 We report on novel COL4A1 mutations occurring de novo in 4 Caucasian patients with extensive prenatal brain destruction, adding to the wide phenotypic spectrum. ### Methods. COL4A1 sequencing was performed according to the Dutch regulations for genetic diagnosis.3 Written informed consent for publication was obtained from the parents. ### Case reports. #### Case 1. This patient (male) presented antenatally at 27 weeks' gestation with asymmetric ventriculomegaly and extensive cerebral infarction seen on fetal ultrasound and MRI (figure 1, A and B). At birth (37 weeks' gestation), apnea, poor feeding, and seizures developed, leading to death at age 10 days. Postnatal cerebral ultrasound (CUS) and postmortem MRI confirmed severe bilateral ventriculomegaly and tissue atrophy after extensive, putatively deep venous infarctions. Absence of the rostral part of the corpus callosum, a poorly gyrated cortex, and atrophy of the basal ganglia, thalami, brainstem, and cerebellum with an enlarged fourth ventricle were noted (figure 1, C and D). Tortuosity of infratentorial and supratentorial vessels (figure 1C), …