Intracranial aneurysms (IA) cause subarachnoid hemorrhage (SAH), which has high mortality and morbidity rates when rupture occurs. The success of genome-wide association studies (GWASs) followed by phenotypic confirmation in transgenic mice has supported the implication of genetic factors in the formation of IA. For example, a Sox17-deficient mouse model was established based on previous GWAS findings, confirming the development of IA resulting in SAH following Sox17 deficiency. The most recent international GWAS identified over half of the disease heritability of IA, including 17 risk loci using more than ten thousand patients. The remaining proportion of heritability, the so-called missing heritability, can be explained by the effects of rare variants detected by next-generation sequencing (NGS). In this review, we discuss the current knowledge regarding genetic factors associated with IAs provided by GWAS and rare variant analysis using NGS.

Background: Surfactants are produced sufficiently after 34 weeks of gestation as the fetal lungs mature. The stable microbubble test (SMT) evaluates fetal lung maturity. However, late preterm infants sometimes present with severe respiratory distress and require appropriate respiratory care.

Methods: We reviewed 42 late preterm infants who underwent the SMT with gastric aspiration upon admission to our neonatal intensive care unit. The gestational age was 35.3 (34.6-36.0) weeks, and the birth body weight was 2,181 (1,971-2,527) g. We classified the patients into the premature and mature groups based on the results of the SMT. We investigated the results of the SMT in late preterm infants and compared lung maturity with the maternal and neonatal respiratory clinical courses.

Results: There were 12 infants in preterm group (28.6%). The gestational age of the premature group was significantly longer, and the Apgar scores were lower in the premature group. Mothers of the premature group had significantly more cases of gestational diabetes mellitus. Respiratory distress syndrome was significantly more frequent, and infants in the premature group required invasive ventilation more frequently.

Conclusions: We found that a small number of neonates produced sufficient surfactant, even in late preterm infants. It is suggested that the production of surfactants is related to gestational diabetes mellitus more than gestational age, and the SMT is useful in late preterm infants.

We report a case of pediatric Fabry disease in a girl whose pain was relieved and quality of life (QOL) improved with enzyme replacement therapy (ERT). Her father was diagnosed with Fabry disease based on the examination findings for pre-renal transplantation due to renal failure. Therefore, examinations were performed for her. Urinary mulberry bodies were positive, and the genetic analysis for α-galactosidase A (GLA) revealed a nonsense variant, leading to the diagnosis of pediatric Fabry disease. At 8 years of age, she presented with pain in the distal portion of the extremities and abdomen, which persisted despite oral carbamazepine. Therefore, ERT was provided. After initiation of ERT, blood lyso-Gb3 levels decreased, and extremity and abdominal pain improved. We asked her and her parent questions about QOL before and 12 months after the start of ERT. The European Quality of Life Five Dimension Youth showed improved scores for usual activities and pain or discomfort, and self-scoring of physical and mental condition on the European Quality of Life Visual Analogue Scale improved from 22 before ERT to 70 after 12 months of ERT. Pediatric Quality of Life also showed improved scores for physical and emotional functioning. Similar results were obtained by questioning the parent. Although the questionnaire is subjective and depends on the patient's physical condition at the time, we speculate that ERT improved QOL. Since the severity of clinical symptoms in women with Fabry disease varies, regular follow-up and appropriate intervention soon after the appearance of organ involvement are important to improve QOL and prevent complications.

Tay-Sachs disease involves accumulation of GM2 gangliosides in lysosomes due to a metabolic disorder of brain-abundant gangliosides. In the infantile type, death typically occurs by 3 years of age. We report brain magnetic resonance imaging (MRI) abnormalities in a case of infantile Tay-Sachs disease. The 8-month-old patient had development delay and began regression at 1 year of age. A cherry-red fundus spot and low β-hexosaminidase A (Hex A) levels in leukocytes indicated GM2 gangliosidosis. Gene analysis identified homozygous pathogenic variants in the HEXA gene, leading to Tay-Sachs disease diagnosis.

At 10 months of age, brain MRI showed age-appropriate myelination. At 1 year 9 months, T2-weighted imaging showed high intensity in the subcortical white matter, with delayed myelination. At 2 years 4 months, the cerebral white matter, putamen, caudate nucleus, thalami (except ventral), middle cerebellar peduncle, and dentate nucleus showed high intensity on T2-weighted imaging. At 5 years 8 months, cerebral and basal ganglia atrophy was observed. The caudate nucleus and putamen showed high intensity on T1-weighted images and low intensity on T2-weighted images. Unlike typical infantile Tay-Sachs characteristics, higher Hex A activity in this case probably contributed to a milder phenotype and myelination acquisition during infancy.