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Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole-exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin-1 heavy chain: two with c.272AG:p.(Lys91Arg), one with c.584CA:p.(Thr195Lys), and the other with c.701GT:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.

Background Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? Methods This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. Results The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (β = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (β = − 0.19) and prematurity (β = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. Conclusions IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

Mother-to-child transmission of the hepatitis B virus (HBV) is a major concern for infected mothers, especially after their first child has become an HBV carrier despite immunoprophylaxis. Eight mothers whose first child had become an HBV carrier despite immunoprophylaxis were referred for antiviral therapy during the subsequent pregnancy. All pregnant women were seropositive for both the hepatitis B surface antigen and hepatitis B e antigen. In the treatment group (three receiving lamivudine and two receiving tenofovir), mother-to-child transmission of the HBV was successfully prevented in all infants (5/5). On the other hand, two of three infants became HBV carriers in the untreated group. There were no significant adverse effects in either mothers or infants. Antiviral therapy using lamivudine and tenofovir during the second pregnancy successfully prevented mother-to-child transmission of the HBV for high-risk mothers.

Background Hydrops fetalis (HF) has low survival rate, particularly in cases of preterm birth. In addition, the severity index of HF has not been fully investigated yet. This study was aimed to clarify the prognostic factors of HF patients with pleural effusion. Methods All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. The prenatal, perinatal, and postnatal information was obtained from their medical records and was retrospectively analyzed. Results Forty-one HF patients with pleural effusion were included, and twenty-eight patients (68%) survived. The multivariate logistic stepwise analysis revealed that the gestational birth week (OR 0.71, 95% CI 0.52–0.96, p = 0.027) and standard deviation (SD) score of the birth weight (OR 1.74, 95% CI 1.01–2.99, p = 0.045) were significant factors for postnatal death. All patients with both >32 gestational weeks and