Congenital Anomalies最新文献

Glycogen storage disease type IXa (GSD IXa) results from a defect in the alpha subunit of phosphorylase kinase encoded by PHKA2 with X-linked inheritance. Clinical manifestations include fasting hypoglycemia, hepatomegaly, and growth failure. Various PHKA2 pathogenic variants have been reported, including microdeletions.¹ To date, few breakpoints have been identified, and mechanisms causing microdeletions are not well understood. We report on a pediatric patient with GSD IXa and a novel microdeletion in PHKA2.

The male proband was the first child of healthy, non-consanguineous Japanese parents. His birth length and weight were 48.4 cm (−0.29 SD) and 2.81 kg (−0.42 SD), respectively. Short stature was noted at 15 months of age; at 18 months, he could not stand alone and motor delay was suspected. He was referred to our hospital at 23 months with length and weight of 79.0 cm (−2.2 SD) and 10.5 kg (−0.82 SD), respectively. He could walk with aid and speak meaning words. Physical examination showed a doll-like appearance, abdominal distension, and hepatomegaly. Laboratory examinations showed as follows: white blood cells, 8800/μL (neutrophils 1584/μL); aspartate aminotransferase, 899 U/L; alanine aminotransferase, 554 U/L; creatine kinase 60 U/L; alkaline phosphatase 966 U/L (age matched reference, 395–1339); γ-glutamyl transpeptidase 374 U/L (reference, 6.5–60.0); creatinine, 0.13 mg/dL; uric acid, 7.0 mg/dL. Fasting glucagon loading test showed glucose of 42 mg/dL (before loading) and 64 mg/dL (60 min after loading). Two-hour postprandial glucagon loading test showed glucose of 131 mg/dL (before loading) and 191 mg/dL (30 min after loading). Oral glucose tolerance tests showed basal lactate and pyruvate levels of 7.0 and 0.61 mg/dL, respectively, and peak lactate and pyruvate levels of 32.2 mg/dL (90 min after loading) and 3.03 mg/dL (30 min after loading), respectively. Computed tomography showed hepatomegaly with high density. Phosphorylase kinase enzyme analysis of red blood cells revealed 0.3 nmoL/min/gHb, compared to 9.1 and 10.1 nmoL/min/gHb in two healthy subjects. We thus diagnosed him as having GSD IXa. After obtaining informed consent from his parents, genomic DNA was extracted from peripheral blood samples of the proband and his mother. We tried to amplify all exons and the flanking introns of the exons in PHKA2 (NM_000292.3) in the proband, but we obtained no polymerase chain reaction (PCR) products of exons 20 and 21. We designed several new forward primers located at the intron intervening exons 19 and 20 and the reverse primer located at exon 22. Using these primers, we performed PCR using DNA from the proband or his mother and obtained the products, with the size at 500–650 bp from the proband and 3000 bp and 500–650 bp from his mother (Figure 1A). The PCR products in the proband were subjected to direct sequencing from both directions on the autosequencer. We identified a

The frequency of cleft lip with/without palate (CL/P) in the Mongolian population is approximately 1 in 1314 live births. This research aims to disseminate information about this congenital disability to the public to better understand CL/P, and people's fissures, and review administrative measures, as there is a lack of research in this area. A questionnaire survey was conducted using Google Forms, with 1000 Mongolian participants. Most participants (86.7%) said they had knowledge of the word, whereas 86.2% said they had knowledge of the condition. Most participants' answers were question-related disadvantages of CL/P patients, including statements such as “It's uncomfortable in human relationships” and “It makes an uncomfortable impression on the person you meet the first time.” The results of this study revealed that most Mongolians were aware of CL/P and are concerned about patients. However, the causes of CL/P in the general population remain unknown, and further research is needed in this area.

The pyramidalis muscle (PM) is a paired small triangular muscle of the anterior abdominal wall; however, its physiological significance is unclear. Recent studies have failed to detect this muscle during embryonic period. Hence, the present study aimed to determine the time when PM is emerging and reveal its features using high-resolution magnetic resonance imaging. Fourteen embryos between Carnegie stage (CS)18 and CS23 and 59 fetuses (crown-rump length: 39.5–185.0 mm) were selected for this study. The PM was first detected in one of the three samples at CS20. It was detected in five of the seven samples (71.4%) between CS21 and CS23. Forty-eight samples (81.4%) at early fetal period had PMs on both the right and left sides, and 3 (5.1%) had it only on the right side. Eight samples (13.6%) had no PMs. No side-differences or sexual dimorphisms were detected. The PM length was larger than the width in most samples, although the length/width ratio varied among the samples. The PM/rectus abdominis muscle length and PM/umbilicus-pubic symphysis length ratios were almost constant, irrespective of the crown-rump length. The PM was located ventrally inferior to the rectus abdominis and closer to the medial muscle groups of the lower limb than the rectus abdominis. The present study demonstrated that PM formation occurred in the late embryonic period, and that the frequency, side differences, sex dimorphism, and spatial position of the PM in the early fetal period were similar to those in adults.

Since pregnant women are excluded from clinical trials, it is essential to accumulate post-marketing information to evaluate the effects on the fetus of medication use during pregnancy. The Japan Drug Information Institute in Pregnancy (JDIIP) was established at the National Center for Child Health and Development as a Ministry of Health, Labour, and Welfare project to provide patients with information and conduct follow-up surveys. In this study, we investigated the status of the accumulation of JDIIP consultation cases to identify issues for enhancing clinical information appropriate for use during pregnancy and to examine how information should be collected and provided. In addition, the status of descriptions of Japanese package inserts, which are representative of those used by healthcare professionals as a source of information, was confirmed for medications used by JDIIP consultation cases. The characteristics of the JDIIP consultation cases information were that the contents that needed to be adjusted when evaluating the effects on the fetus of medication use during pregnancy were obtained. In addition, the follow-up rate was 83.1%. However, although the number of consultation facilities has increased, the number of consultations has not, indicating the need to further increase the number. It was found that there is limited information on epidemiological studies of clinical use in Japanese package inserts. To improve clinical information on the appropriate use of medications during pregnancy, it is necessary to accumulate more information in the future, and it is considered necessary to consider new approaches utilizing the JDIIP system.

Congenital tracheal stenosis is a rare life-threatening disorder caused by narrow O-shaped tracheal ring without smooth muscle. Its underlying genetic cause has not been elucidated. We performed whole exome sequencing in a patient with congenital tracheal stenosis and congenital heart defect, and identified a de novo pathogenic TBX5 variant (NM_181486.4:c.680T>C, p.(Ile227Thr)). The Ile227Thr-TBX5 protein was predicted to have a decreased stability by in silico protein structural analyses, and was shown to have a significantly reduced activity for the NPPA promoter by luciferase assay. The results, together with the expression of mouse Tbx5 in the lung and trachea and the development of tracheal cartilage dysplasia in the lung-specific Tbx5 null mice, imply the relevance of TBX5 pathogenic variants to congenital tracheal stenosis.

The objective of the study was to examine the association of congenital anomalies with the specific classes of pre-pregnancy BMI. An IRB-approved retrospective cohort study was performed using the data from the Natality Public Use File from the National Center for Health Statistics (2019). We included all singleton live births and excluded pregnancies with suspected or confirmed chromosomal abnormalities and people with pre-existing diabetes mellitus and missing pertinent data. The primary outcome was the incidence of any major congenital anomalies in liveborn infants. The incidence of anomaly was analyzed across all BMI classes, using individuals with BMI between 18.5 and 24.9 kg/m² as the comparison group. A test of trend was also performed to determine if the risk increased as the BMI class increased. A total of 3 047 382 maternal-neonatal dyads were included in the analysis. A non-significant higher incidence of any major anomaly was noted among people who had underweight and class III BMI. The risk of open neural tube defects, omphalocele, and cleft lip/palate increased and the risk of gastroschisis decreased with an increase in maternal BMI class (p < 0.05). The incidence of congenital anomalies increases as the pre-pregnancy BMI increases. Individuals should be encouraged to optimize their weight prior to conception and if feasible, they should obtain screening for fetal anatomy assessment by a Maternal-Fetal Medicine specialist.

Since telepractice regulation does not yet exist in Japan, we assessed telepractice efficacy and the level of satisfaction with telepractice versus that with face-to-face practice (FTFP) in speech therapy to establish effective telepractice in Japan. Changes in the number of therapy sessions and therapy levels were compared between telepractice and FTFP sessions conducted during the study period. Additionally, the patients' parents completed a questionnaire survey regarding telepractice. The mean number of sessions was not significantly different between the two types of therapy; the therapy levels, according to stepwise speech therapy, either increased or remained unchanged. The survey showed satisfaction with telepractice among all parents. Telepractice for cleft palate speech was delivered successfully with complete parental satisfaction.