ABSTRACT
Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G. Based on the manifestations in the Finnish and Amish individuals, the hallmarks of CHH are prenatal-onset growth failure, metaphyseal dysplasia, hair hypoplasia, immunodeficiency, and other extraskeletal manifestations. Herein, we report six Japanese individuals with CHH from four families. All probands presented with moderate short stature with mild metaphyseal dysplasia or brachydactyly. One of them had hair hypoplasia and the other immunodeficiency. By contrast, the affected siblings of two families showed only mild short stature. We also reviewed all previously reported 13 Japanese individuals. No n.71A > G allele was detected. The proportions of Japanese versus Finnish individuals were 0% versus 70% for birth length < -2.0 SD, 84% versus 100% for metaphyseal dysplasia and 26% versus 88% for hair hypoplasia. Milder manifestations in the Japanese individuals may be related to the difference of genotypes. The mildest form of CHH phenotypes is mild short stature without overt skeletal alteration or extraskeletal manifestation and can be termed "RMRP-related short stature".
Subject(s)
Hair , Hair/abnormalities , Osteochondrodysplasias , Osteochondrodysplasias/congenital , Humans , Female , Male , Osteochondrodysplasias/genetics , Osteochondrodysplasias/pathology , Hair/pathology , Child , Hirschsprung Disease/genetics , Hirschsprung Disease/pathology , Hirschsprung Disease/diagnosis , Dwarfism/genetics , Dwarfism/pathology , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/pathology , Child, Preschool , Phenotype , Japan/epidemiology , RNA, Long Noncoding/genetics , Pedigree , Mutation/genetics , Alleles , Adolescent , Genotype , East Asian PeopleABSTRACT
INTRODUCTION: Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. METHODS: A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. RESULTS: Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36-1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: -0.63-0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: -7.12-15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. CONCLUSION: The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children.
Subject(s)
Ductus Arteriosus, Patent , Respiration, Artificial , Infant , Child , Infant, Newborn , Humans , Respiration, Artificial/adverse effects , Fentanyl/therapeutic use , Infant, Premature , Ductus Arteriosus, Patent/drug therapy , Cerebral Hemorrhage , Pain/drug therapy , Pain/etiologyABSTRACT
Miller-Dieker syndrome represents a microdeletion syndrome spanning the LIS1 locus at 17p13.3, the deletion of which leads to lissencephaly. A fluorescence in situ hybridization study using an LIS1 probe is considered the standard laboratory diagnostic method for Miller-Dieker syndrome. This report documents a Miller-Dieker syndrome patient who tested normal when a commercially available LIS1 fluorescence in situ hybridization study probe was used but was later demonstrated to have a partial deletion of the LIS1 locus. The present case exemplifies a major shortcoming of commercially available fluorescence in situ hybridization studies for the diagnosis of microdeletion syndromes such as Miller-Dieker syndrome: that is, relatively small deletion can potentially remain undetected.
