Progressive cerebral atrophies in three children with COL4A1 mutations.

BACKGROUND: The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic conditions in humans, including the brain, eyes, kidneys, muscles, and other organs at any age. Brain imaging shows a wide spectrum of abnormalities, including porencephaly, schizencephaly, polymicrogyria focal cortical dysplasia, periventricular leukoencephalopathy, ventricular dysmorphisms, and multiple brain calcifications. However, there are no reports in the literature showing progressive radiological findings in consecutive follow-up scans. Herein, we report three cases of COL4A1 mutations with porencephaly from gestation to five years of age or longer, and describe their clinical and brain imaging findings. CASE REPORTS: We retrospectively reviewed the clinical symptoms and radiological findings, including brain magnetic resonance imaging (MRI) and computed tomography (CT), in three female patients with COL4A1 mutations. Their mutations were c.4843G>A (p.Glu1615Lys), c.1835G>A (p.Gly612Asp), and c.3556+1G>T respectively. All the three cases represented porencephaly in the fetal period; severe hemolytic anemia in the neonatal period; and drug-resistant epilepsy, global developmental delay, and spastic quadriplegia in their childhood. RESULTS: Brain MRI and CT showed progressive white matter atrophy from gestation to five-year follow-up or later. Minor cerebral hemorrhage without symptoms occasionally occurred in one patient. Despite brain changes, the clinical picture was stable during early childhood. CONCLUSIONS: COL4A1 mutations may cause progressive cerebral atrophy beyond early childhood.

Identification of sleep hypoventilation in young individuals with Becker muscular dystrophy: A pilot study.

AIM: To report on sleep hypercapnia in Becker muscular dystrophy (BMD) at earlier stages than ever recognized. SUBJECTS AND METHODS: This retrospective study examined nocturnal hypercapnia in six young Becker muscular dystrophy (BMD) patients with deletions of one or more exons of DMD gene. Clinical information, consecutive data on forced vital capacity (FVC%), forced expiratory volume in one second (FEV1%), peak expiratory flow (PEF%), peak cough flow (PCF), average PCO2 in all-night monitoring, and left ventricular ejection fraction (LVEF) were reviewed. RESULTS: In five BMD patients, including three who were still ambulant, nocturnal average PCO2 was elevated to >45 mmHg at 12-31 years of age. Noninvasive positive pressure ventilation was initiated in four patients. Gradual declines in FVC% and PEF% were evident in one BMD patient with exon 3-7 deletion, whereas these functions did not change in the remaining BMD patients. PCF, FEV1%, and LVEF were less informative for the assessment of respiratory function in this patient series. CONCLUSION: Sleep hypercapnia was present in certain BMD patients, which was unexpected from the routine pulmonary function tests. Individualized assessment of nocturnal PCO2, partly based on the deletion types, should be further explored in the clinical practice of BMD patients.