Primordial dwarfism (PD) refers to a group of monogenic genetic disorders characterized by intrauterine growth restriction (IUGR) and severe, persistent postnatal growth retardation. These diseases have been associated with variants of multiple genes whose products are mainly involved in critical cellular biological processes such as maintenance of genomic stability, DNA damage repair, mRNA splicing regulation, and centrosome function. Variants of such genes can directly impair cell proliferation and developmental potential. With the widespread application of molecular genetic technologies such as high-throughput sequencing, significant progress has been made in the research of PD. This article focuses on the major subtypes of PD, including Seckel syndrome, Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, MOPD type II, and Meier-Gorlin syndrome. It has systematically summarized the advances in their clinical phenotypic characteristics, pathogenic genes, and molecular mechanisms, with an aim to deepen the understanding of the essence of growth disorders associated with PD.
Humans ; Dwarfism/genetics* ; Microcephaly/genetics* ; Phenotype ; Fetal Growth Retardation/genetics* ; Osteochondrodysplasias/genetics* ; Growth Disorders ; Micrognathism ; Patella/abnormalities* ; Congenital Microtia

OBJECTIVE: To investigate the clinical characteristics, steroid hormone profiles, and genetic variants in two female patients with Non-classic adrenal hyperplasia (NCAH). METHODS: Clinical data and samples were collected from two patients who had visited Huaian Maternal and Child Health Care Hospital Affiliated to Medical College of Yangzhou University on September 27, 2022 and June 25, 2023, respectively, with an initial diagnosis of Polycystic ovary syndrome (PCOS) and suspected NCAH. Seven steroid hormones in dried blood spots were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Single base variants and repeat/deletions in the CYP21A2 gene were analyzed by using a classic congenital adrenal hyperplasia (CAH) gene assay, and 10 related genes were analyzed by third-generation sequencing (TGS) should the variants be unclear. This study has been approved by the Medical Ethics Committee of the hospital (Ethics No.: 2025003). RESULTS: Patient 1 was a 14-year-old girl, and patient 2 was a 23-year-old woman with insulin resistance. Both patients had hirsutism, acne, bilateral polycystic ovarian morphology, in addition with significantly elevated serum testosterone by chemiluminescence. The steroid hormone profiles of both patients suggested a significant increase in 17-hydroxyproesterone, normal cortisol and 11-deoxycortisol. Patient 2 additionally showed a significant rise in 21-deoxycortisol. The presentation of both patients was indicative of NCAH, which was also evidenced by their respective medical histories. Sanger sequencing of long fragment PCR amplification combined with multiplex ligation-dependent probe amplification (MLPA) revealed that patient 1 harbored a mild c.92C>T (p.P31L) variant and a severe variant with a large segmental deletion in CYP21A2. Patient 2 was finally confirmed by TGS to carry mild CYP21A2 variants in the 5' untranslated region (5' UTR) promotor region (c.-126C>T, c.-113G>A, c.-110T>C) and a severe c.293-13C/A>G variant. The promotor region variants had resulted in decompression of the long fragment P1X/P2 amplification, leading to homozygous result of Sanger sequencing for c.293-13C/A>G, which in turn halved the amplification signal for the wt-113 SNP probe. In addition, the wtI2G-A probe was enhanced by interference in the MLPA assay. CONCLUSION This study demonstrated that NCAH should be excluded when PCOS is accompanied by a significant increase in serum testosterone, that mass spectrometry of steroid hormone profiles containing 17-hydroxyprogesterone is useful for the detection of NCAH, and that TGS is advantageous in confirming the diagnosis of NCAH when compared with conventional genetic testing methods.
Humans ; Female ; Adrenal Hyperplasia, Congenital/blood* ; Adolescent ; Steroid 21-Hydroxylase/genetics* ; Young Adult ; Genetic Variation ; Adult

BACKGROUND AND OBJECTIVE

Pediatric post-operative congenital diaphragmatic hernia (CDH) patients have been shown to encounter reduced pulmonary function tests (PFT) potentially leading to respiratory symptoms. Strategies involving exercise have been used to improve PFT. This meta-analysis aims to determine the effectiveness of exercise in improving lung function in pediatric post-operative CDH patients.

An electronic search was done on May 2023 in MEDLINE via Pubmed, Cochrane Library, Embase, ClinicalKey, Scopus, Google Scholar, and Herdin Plus, using the search terms "exercise" and "congenital diaphragmatic hernia" and "children" or "pediatric" and "pulmonary function" or "lung function". The study included pediatric patients in whom CDH has been surgically corrected, and excluded patients who were unable to perform the test maneuvers, have cardiopulmonary instability, and have serious associated anomalies. Randomized controlled trials (RCT) were identified and independently assessed by two review authors. Each RCT was independently assessed for bias by two review authors using the Cochrane Handbook for Systematic Reviews of Interventions. The RevMan 5.4 software was used for statistical analysis.

A total of 124 participants from three studies were included in the meta-analysis. The pooled mean difference showed a significantly higher mean functional vital capacity (FVC) (MD=6.12, 95%CI=3.91 to 8.33, p-value < 0.00001) and forced expiratory volume in 1 second (FEV1 ) (MD=6.25, 95%CI=3.39 to 9.10, p-value < 0.0001) in the study group compared to the control group.

Exercise may be effective in improving lung function in children with pediatric post-operative CDH. However, the study is limited by its small sample size, the lack of assessment of long-term outcomes, and the difference in exercise regimens used in each RCT. Further studies are recommended to determine the most optimal exercise regimen and to measure its effect on the other outcomes for this population.

BACKGROUND

Persistent left superior vena cava (PLSVC) is a rare but clinically relevant congenital vascular anomaly, occurring in 0.3% of the general population and up to 4.3% in those with congenital heart disease. It is usually asymptomatic and incidentally discovered during imaging, catheterization, or surgery.

We present the case of a 38-year-old hypertensive female who was evaluated for acute chest discomfort, palpitations and near-syncope. Transthoracic echocardiography revealed a dilated coronary sinus, prompting a contrast echocardiography study that demonstrated early opacification of the coronary sinus upon left arm injection confirming the diagnosis of PLSVC.

This case underscores the importance of recognizing coronary sinus dilatation as a potential marker of venous anomalies such as PLSVC. Contrast echocardiography with bilateral injections remains a practical, non-invasive tool in its diagnosis, with significant implications for future invasive procedures.

Congenital musculoskeletal and limb deformities (CMLD) seriously affect the physical and mental health of patients, and pose great challenges to healthcare systems worldwide. We explored the specific situation and changes of incidence, prevalence, disability-adjusted life years rates, and mortality of CMLD in under-5 children from 1990 to 2021 in different groups, including different regions, periods, genders and socio-demographic indices (SDI), through corresponding analytical models. Overall, the global disease burden of CMLD in under-5 children has decreased from 1990 to 2021. The disease burden of CMLD in under-5 children varied significantly among different regions and countries, and there was a strong correlation between the corresponding burden of disease and the level of SDI. In addition, cross-country inequality analysis showed that while absolute inequalities in the disease burden of CMLD in under-5 children have improved, relative inequalities have worsened. It is essential to reduce the global health impact of CMLD by implementing targeted interventions to improve health care in underdeveloped areas.
Humans ; Global Burden of Disease/trends* ; Child, Preschool ; Global Health/statistics & numerical data* ; Infant ; Male ; Prevalence ; Limb Deformities, Congenital/mortality* ; Musculoskeletal Abnormalities/mortality* ; Female ; Disability-Adjusted Life Years ; Incidence ; Infant, Newborn ; Cost of Illness ; Socioeconomic Factors

BACKGROUND AND OBJECTIVE

Transient congenital hypothyroidism (TCH) refers to temporary deficiency of thyroid hormone identified after birth which later recovers to improved thyroxine production. Its prevalence in the Philippines has not been reported in a large-scale study. Its diagnosis remains difficult due to its numerous possible etiologies. Identifying the predictive factors of TCH may aid in earlier diagnosis and decreased risk of overtreatment. This study aimed to determine the predictive factors for TCH in children with congenital hypothyroidism (CH) detected by newborn screening (NBS) in the Philippines from January 2010 to December 2017.

In this multicenter retrospective cohort study involving 15 NBS continuity clinics in the Philippines, medical records were reviewed, and clinical and laboratory factors were compared between children with TCH and those with permanent congenital hypothyroidism (PCH). Of the 2,913 children diagnosed with CH in the Philippines from 2010 to 2017, 1,163 (39.92%) were excluded from the study due to an unrecalled or lost to follow-up status, or a concomitant diagnosis of Down Syndrome.

Among the 1,750 patients included in analysis, 6.97% were diagnosed with TCH, 60.80% were female, mean gestational age at birth was 38 weeks, and mean birth weight was 2,841 grams. Confirmatory thyrotropin (TSH) was lower and confirmatory free thyroxine (FT4) was higher in the TCH group compared to those with PCH (TSH 32.80 vs 86.65 µIU/mL [p < 0.0001]; FT4 9.90 vs 7.37 pmol/L [p 0.001]). The TCH group required lower L-thyroxine doses compared to the PCH group at treatment initiation and at 1, 2, and 3 years of age (initial 6.98 vs 12.08 µg/ kg/day [p < 0.0001]; at 1 year 1.89 vs 4.11 µg/kg/day [p < 0.0001]; at 2 years 1.21 vs 3.72 µg/kg/day [p < 0.0001]; at 3 years 0.83 vs 3.45 µg/kg/day [p < 0.0001]). Among those with TCH, mean serum TSH decreased significantly after treatment with L-thyroxine (32.80 vs. 6.55 µIU/ mL, p 0.0001). Other factors associated with TCH were results of thyroid ultrasonography (p 0.007), gestational age at birth (p 0.02), and maternal history of thyroid illness (p < 0.0001).

Of all the patients with confirmed congenital hypothyroidism via the newborn screening, 6.97% were diagnosed with transient CH. Factors associated with TCH are confirmatory TSH and FT4, L-thyroxine dose requirements, thyroid ultrasound findings, gestational age at birth, and a maternal history of thyroid illness.

BACKGROUND AND OBJECTIVE

Mothers play a significant role as primary caregivers for children with congenital heart disease (CHD) within the family. Given the complex health needs of children with CHD, coping strategies are needed to deal with the challenges associated with caring for their children with the condition. Coping mechanisms encompass fostering resilience, seeking support, and maintaining a positive outlook to navigate stress, uncertainty, and obstacles throughout their child's medical journey with CHD. The objective of this study is to explore the coping strategies employed by mothers of children diagnosed with CHD in a tertiary hospital in the Philippines.

Employing a descriptive qualitative study design, data was gathered through key informant interviews utilizing a semi-structured topic guide, which aimed to explore the perspectives and experiences of mothers with children with CHDs. Ethical approval was obtained, and data collection occurred from January to March 2016. Interview transcripts were recorded, transcribed verbatim, and underwent content analysis. Themes derived from the analysis were then validated and confirmed by the study participants.

A total of 11 mothers voluntarily participated in the study. These participants expressed utilizing various coping strategies to manage their child's condition, including seeking assistance from both physicians and traditional healers, advocating for their children, receiving support from their family and friends, regulation of emotion, and prayer and faith in God.

This study sheds light on the coping mechanisms used by mothers in raising thier children with CHD, highlighting the value of spirituality and psychological support in their journey. Enhancing assistance for impacted families and advancing genetic counseling services are two benefits of incorporating these findings into healthcare practice.

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

Mitochondrial neurogastrointestinal encephalomyopathy(MNGIE),a rare mitochondrial disorder caused by TYMP gene mutations,is characterized by severe gastrointestinal dysmotility,peripheral neuropathy,and leukodystrophy.This article summarizes the clinical data and intestinal ultrasound findings of a MNGIE case,aiming to provide insights for clinical diagnosis and treatment.
Humans ; Mitochondrial Encephalomyopathies/diagnostic imaging* ; Ultrasonography ; Intestines/diagnostic imaging* ; Male ; Female ; Intestinal Pseudo-Obstruction/diagnostic imaging* ; Ophthalmoplegia/congenital* ; Muscular Dystrophy, Oculopharyngeal

OBJECTIVE: To investigate the effectiveness of Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy in treating Tönnis type Ⅲ and Ⅳ developmental dysplasia of the hip (DDH) in children and explore the urgical timing. METHODS: A retrospective collection was performed for 74 children with Tönnis type Ⅲ and Ⅳ DDH who were admitted between January 2018 and January 2020 and met the selection criteria, all of whom were treated with Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy. Among them, there were 38 cases in the toddler group (age, 18-36 months) and 36 cases in the preschool group (age, 36-72 months). There was a significant difference in age between the two groups ( P<0.05), and there was no significant difference in gender, side, Tönnis typing, and preoperative acetabular index (AI) ( P>0.05). During follow-up, hip function was assessed according to the Mckay grade criteria; X-ray films were taken to observe the healing of osteotomy, measure the AI, evaluate the hip imaging morphology according to Severin classification, and assess the occurrence of osteonecrosis of the femoral head (ONFH) according to Kalamchi-MacEwen (K&M) classification criteria. RESULTS: All operations of both groups were successfully completed, and the incisions healed by first intention. All children were followed up 14-53 months, with an average of 27.9 months. There was no significant difference in the follow-up time between the two groups ( P>0.05). At last follow-up, the excellent and good rates according to the Mckay grading were 94.73% (36/38) in the toddler group and 83.33% (30/36) in the preschool group, and the difference between the two groups was significant ( P<0.05). The imaging reexamination showed that all osteotomies healed with no significant difference in the healing time between the two groups ( P>0.05). There was no significant difference in AI between the two groups at each time point after operation ( P>0.05), and the AI in the two groups showed a significant decreasing trend with time extension ( P<0.05). The result of Severin classification in the toddler group was better than that in the preschool group at last follow-up ( P<0.05). There was no significant difference in the incidence of ONFH between the two groups ( P>0.05). In the toddler group, 2 cases were K&M type Ⅰ; in the preschool group, 3 were type Ⅰ, and 1 type Ⅱ. There was no dislocation after operation. CONCLUSION Salter osteotomy combined with subtrochanteric shortening and derotational osteotomy is an effective way to treat Tönnis type Ⅲ and Ⅳ DDH in children, and surgical interventions for children aged 18-36 months can achieve better results.
Humans ; Osteotomy/methods* ; Developmental Dysplasia of the Hip/diagnostic imaging* ; Retrospective Studies ; Male ; Child, Preschool ; Female ; Infant ; Femur/surgery* ; Child ; Treatment Outcome ; Hip Dislocation, Congenital/surgery*