Porencephaly is a neurologic disorder characterized by fluid-filled cysts or cavities in the brain and is thought to result from disturbed vascular supply leading to cerebral degeneration. Affected individuals typically have hemiplegia, seizures, and intellectual disability, although the ... Porencephaly is a neurologic disorder characterized by fluid-filled cysts or cavities in the brain and is thought to result from disturbed vascular supply leading to cerebral degeneration. Affected individuals typically have hemiplegia, seizures, and intellectual disability, although the severity is variable (summary by Yoneda et al., 2012). For a discussion of genetic heterogeneity of porencephaly, see POREN1 (175780).
Yoneda et al. (2012) reported a Japanese family with autosomal dominant inheritance of porencephaly of varying severity. The proband was found to have an enlarged right lateral ventricle at age 31 weeks' gestation. He showed delayed early development, ... Yoneda et al. (2012) reported a Japanese family with autosomal dominant inheritance of porencephaly of varying severity. The proband was found to have an enlarged right lateral ventricle at age 31 weeks' gestation. He showed delayed early development, particularly of motor skills, with poor left hand use, abnormal leg movement, and delayed walking. At age 3, he showed spastic triplegia with left hemiplegic and diplegic gait. He developed seizures at age 10 months, and EEG showed focal spikes in the right frontal region, with later involvement of the right occipital to posterior temporal region and midcentral region. Brain MRI at age 6 years showed an enlarged right lateral ventricle, reduced volume of the right frontal white matter, and atrophic right cerebral peduncle and body of corpus callosum. IQ was 74. His mother had focal seizures at age 18 months, which were well-controlled. She had clumsiness of the left hand in later childhood, as well as transient headaches. At age 31 years, she had very mild monoparesis of the left upper extremity. Brain MRI showed a mildly enlarged right lateral ventricle, and evidence of mild porencephaly or periventricular venous infarction around the enlarged ventricular wall on FLAIR imaging. The proband's maternal uncle and maternal granduncle also had a history of congenital hemiplegia, suggesting a genetic predisposition in the family. A second unrelated Japanese proband was severely affected. He had low APGAR scores and mild asphyxia at birth. Brain ultrasound showed a parenchymal hemorrhage of the right cerebral hemisphere with an enlarged left lateral ventricle. He also showed a coagulation defect, with increased PT and APTT, and received fresh frozen plasma. The coagulation defect normalized at age 7 months. At age 37 days, he had a ventricular shunt placed for progressive enlargement of the lateral ventricles. CT scan at age 2 months showed extremely reduced white matter in the frontal lobes. At age 1 year, 4 months, he had spastic quadriplegia and very poor development. An elder sister had an intraventricular hemorrhage 2 days after birth and underwent ventriculoperitoneal shunting. Her development was almost normal, although internal strabismus was noted. However, she died in an accident at the age of 4 years, and DNA was unavailable.
In affected members of a family with porencephaly-2, Yoneda et al. (2012) identified a heterozygous mutation in the COL4A2 gene (G1152D; 120090.0001). A second heterozygous de novo mutation (G1037E; 120090.0002) was found in an unrelated Japanese boy with ... In affected members of a family with porencephaly-2, Yoneda et al. (2012) identified a heterozygous mutation in the COL4A2 gene (G1152D; 120090.0001). A second heterozygous de novo mutation (G1037E; 120090.0002) was found in an unrelated Japanese boy with porencephaly. Overall, these mutations were found in 2 of 35 Japanese patients with porencephaly. COL4A2 was selected as a candidate for sequencing since COL4A1, with which it forms a heterotrimer, causes POREN1.