Tsuyoshi Isojima

New reference growth charts for Japanese girls with Turner syndrome

Background:  Currently used growth charts for Japanese girls with Turner syndrome (TS) were constructed with auxological data obtained before the secular trend in growth reached a plateau. These charts were published in 1992 and may no longer be valid for the evaluation of stature and growth in girls with TS in clinical settings. Thus, we need to establish new clinical growth charts.

Growth standard charts for Japanese children with mean and standard deviation (SD) values based on the year 2000 national survey

Growth charts are essential and universally used for evaluating growth and development of children in both clinical settings and in public health examinations (1, 2). We previously reported the growth standards for Japanese children with percentile values based on the year 2000 national survey data (3), which were established by the lambda-mu-sigma (LMS) method (4). These standards have been widely used mainly in public health examinations. In clinical practices, Japanese physicians preferably assess growth with standard deviation (SD) scores, because many physicians feel that percentiles are not suitable for monitoring children with extreme growth retardation. Considering this, we created practical growth charts with mean and SD values, based on the criteria of the national medical aid program for specific pediatric chronic diseases by using the eye-fitting method (5). Although these charts have been widely used in clinical settings, they do not reflect the correct distributions of height and weight for Japanese children, especially the weight chart. Weight is not usually distributed normatively, but the practical weight chart was made with the assumption of a normal distribution. To this end, we saw the need for growth standards that can be used appropriately both for clinical and public health purposes. Therefore, we reanalyzed the previously reported growth standard charts with percentile values (3) and constructed the growth standards with mean and SD values for Japanese children, which would be applicable not only for clinical practices but also for public health examinations.

Impact of the great east Japan earthquake on the body mass index of preschool children: a nationwide nursery school survey

Objective To evaluate the impact of the 2011 great east Japan earthquake on body mass index (BMI) of preschool children. Design Retrospective cohort study and ecological study. Setting Affected prefectures (Fukushima, Miyagi and Iwate) and unaffected prefectures in northeast Japan. Participants The cohort study assessed 2033 and 1707 boys and 1909 and 1658 girls in 3 affected prefectures and unaffected prefectures, respectively, all aged 3–4 years at the time of the earthquake. The ecological study examined random samples of schoolchildren from the affected prefectures. Primary and secondary outcome measures The cohort study compared postdisaster changes in BMIs and the prevalence of overweight and obese children. The ecological study evaluated postdisaster changes in the prevalence of overweight children. Results 1 month after the earthquake, significantly increased BMIs were observed among girls (+0.087 kg/m2 vs unaffected prefectures) in Fukushima and among boys and girls (+0.165 and +0.124 kg/m2, respectively vs unaffected prefectures) in Iwate. 19 months after the earthquake, significantly increased BMIs were detected among boys and girls (+0.137 and +0.200 kg/m2, respectively vs unaffected prefectures) in Fukushima, whereas significantly decreased BMIs were observed among boys and girls (−0.218 and −0.082 kg/m2, respectively vs unaffected prefectures) in Miyagi. 1 month after the earthquake, Fukushima, Miyagi and Iwate had a slightly increased prevalence of overweight boys, whereas Fukushima had a slightly decreased prevalence of overweight girls, compared with the unaffected prefectures. The ecological study detected increases in the prevalence of overweight boys and girls in Fukushima who were 6–11 and 6–10 years of age, respectively. Conclusions These results suggest that in the affected prefectures, preschool children gained weight immediately after the earthquake. The long-term impact of the earthquake on early childhood growth was more variable among the affected prefectures, possibly as a result of different speeds of recovery.

Proposal of New Auxological Standards for Japanese Girls with Turner Syndrome

We recently published new reference growth charts for Japanese girls with Turner syndrome (TS) based on the cross-sectional data of 1,447 subjects beyond the secular trend of growth in Japan. This study was undertaken for their validation and, if necessary, modification before general application. For validation, 24 subjects who had data both at younger (≤5 yr) and older ages (≥13 yr) were used. We analyzed the concordance/discordance of their height standard deviation score (SDS) defined by the charts between the two age periods. For modification, the LMS method was used with 5,772 longitudinal measurements obtained both from the previously analyzed subjects and 118 newly recruited subjects who had been followed up at the National Center for Child Health and Development or Toranomon Hospital. Significant and critical discordance (mean difference, 1.95 SDS; 95% confidence interval (CI), 1.53–2.36; p<0.0001) was detected in height SDS. This prompted us to perform the modifications. A similar analysis using the modified charts revealed no significant discordance (mean difference, 0.27 SDS; 95%CI: –0.17 – 0.71; p=0.22). They seem more adequate for clinical applications for girls with TS born after 1970. New auxological standards for Japanese girls with TS were proposed.

Inconsistent determination of overweight by two anthropometric indices in girls with Turner syndrome

Aim: To evaluate the prevalence of overweight in girls with Turner syndrome (TS) as classified by the two major anthropometric indices, body mass index (BMI) and weight‐for‐height (WFH) and to make growth reference charts of them for comparison with those of the normal population.

Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array

Context Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR) gene. No patients have been reported with uniparental disomy (UPD). Objective Using genome-wide single nucleotide polymorphism (SNP) array to confirm whether HVDRR was caused by UPD of chromosome 12. Materials and Methods A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array. Results The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father’s allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents) showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium. Conclusions This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

Growth references for Japanese individuals with Noonan syndrome

Background:Noonan syndrome (NS) is a clinically and genetically heterogeneous syndrome characterized by distinctive facial features, short stature, congenital heart diseases, and other comorbidities. NS-specific growth charts are essential for NS care, but currently no such charts are available for Asian populations.Methods:We conducted a nationwide survey by collaborating with three academic societies in Japan. We obtained the data of 356 clinically diagnosed NS subjects from 20 hospitals. The Lambda-Mu-Sigma method was used for establishing growth charts.Results:A total of 308 subjects (males: 159 and females: 149) were analyzed after excluding 48 subjects because of missing auxological data (26 subjects), presence of complications affecting growth (5 subjects), and extreme longitudinal growth aberrations which lay more than three standard deviation scores from the mean in this population (17 subjects). Genetic analyses were performed in 150 patients (48.7%); 103 (68.7%) were reported to have some abnormalities in the known causative genes. Cardiovascular diseases were found in 256 patients (83.1%). The NS-specific height, weight, and BMI charts were constructed with 3,249 mixed longitudinal and cross-sectional measurements.Conclusion:Growth standards for Japanese individuals with NS were established. These charts are expected to be used in various clinical settings.

Disease-specific Growth Charts of Marfan Syndrome Patients in Korea

Patients with Marfan syndrome (MFS) presents with primary skeletal manifestations such as tall stature, chest wall abnormality, and scoliosis. These primary skeletal manifestations affect the growth pattern in MFS. Therefore, it is not appropriate to use normal growth charts to evaluate the growth status of MFS. We aimed to develop disease-specific growth charts for Korean MFS patients and to use these growth charts for understanding the growth patterns in MFS and managing of patients with MFS. Anthropometric data were available from 187 males and 152 females with MFS through a retrospective review of medical records. Disease-specific growth charts were generated and 3, 25, 50, 75, and 97 percentiles were calculated using the LMS (refers to λ, μ, and σ, respectively) smoothing procedure for height and weight. Comparisons between MFS patients and the general population were performed using a one-sample t-test. With regard to the height, the 50th percentile of MFS is above the normative 97th percentile in both genders. With regard to the weight, the 50 percentile of MFS is above the normative 75th percentile in male and between the normative 50th percentile and the 75th percentile in female. The disease-specific growth charts for Korean patients with MFS can be useful for monitoring growth patterns, planning the timing of growth-reductive therapy, predicting adult height and recording responses to growth-reductive therapy.

Alterations in physique among young children after the Great East Japan Earthquake: Results from a nationwide survey

Background Data for earthquake-related alterations in physique among young children in developed countries is lacking. The Great East Japan Earthquake caused severe damage in Iwate, Miyagi, and Fukushima Prefectures in northeastern Japan. Methods We retrospectively obtained anthropometric measurements in nursery school from 40,046 (cohort 1, historical control) and 53,492 (cohort 2) children aged 3.5–4.5 years without overweight in October 2008, and in October 2010, respectively. At the time of the earthquake in March, 2011, children in cohort 1 had already graduated from nursery school; however, children in cohort 2 were still enrolled in nursery school at this time. We compared the onset of overweight at 1 year after the baseline between children enrolled in their school located in one of the three target prefectures versus those in other prefectures using a logistic regression model, with adjustment for sex, age, history of disease, and obesity index at baseline. Overweight was defined as an obesity index of >+15%, which was calculated as (weight minus sex- and height-specific standard weight)/sex- and height-specific standard weight. Results The odds ratio (OR) for the onset of overweight in the three target prefectures was significant in cohort 2 (OR 1.25; 95% confidence interval [CI], 1.01–1.55) but not in cohort 1. When the two cohort were pooled (n = 93,538), the OR of the interaction term for school location × cohort was significant (OR 1.56; 95% CI, 1.09–2.23). Conclusions Incident overweight in young children was significantly more common in the three prefectures affected by the Great East Japan Earthquake than in other prefectures after the disaster.

Longitudinal changes in body mass index of children affected by the Great East Japan Earthquake

Background:The evacuation and disruption in housing caused by the 2011 Great East Japan Earthquake and following nuclear radiation may have influenced child health in many respects. However, studies regarding longitudinal childhood growth are limited. Therefore, in this study we aimed to explore the influence of the earthquake on longitudinal changes in body mass index in preschool children.Methods:Participants were children from nursery schools who cooperated with the study in the Iwate, Miyagi and Fukushima prefectures. The exposed group consisted of children who experienced the earthquake during their preschool-age period (4–5 years old). The historical control group included children who were born 2 years earlier than the exposed children in the same prefectures. Trajectories regarding body mass index and prevalence of overweight/obesity were compared between the two groups using multilevel analysis. Differences in the changes in BMI between before and after the earthquake, and proportion of overweight/obesity was compared between the two groups. We also conducted subgroup analysis by defining children with specific personal disaster experiences within the exposed group.Results:A total of 9722 children were included in the study. Children in the exposed group had higher body mass indices and a higher proportion of overweight after the earthquake than the control group. These differences were more obvious when confined to exposed children with specific personal disaster experiences.Conclusions:Children’s growth and development-related health issues such as increased BMI after natural disasters should evoke great attention.