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.

Distal vaginal agenesis (DVA) is a rare form of female genital tract malformation that presents as cryptomenorrhea. It results from the failure of the urogenital sinus to form the caudal portion of the vagina. Through a thorough history, physical examination and appropriate imaging studies, an accurate diagnosis is integral in selecting the correct intervention for the patient. This is a case of distal vaginal agenesis in a 10-year-old nulligravid, who presented with fecal retention from an abdominopelvic mass. The patient had no bowel movement for four days, and abdominal enlargement. On inspection, there was a 12.0cm x 10.0cm palpable abdominal mass. Inspection of the external genitalia, the introitus appeared concave, with no appreciable introital opening. On digital rectal examination, an anterior bulge was palpated 0.5 cm from the anal verge. A pull-through vaginoplasty was performed with an unremarkable post-operative course. The patient was discharged with a patent vagina and resolution of her gastrointestinal symptoms. On follow-up, the patient had monthly menstruation after surgery with no recurrence of her gastrointestinal symptoms.

BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

BACKGROUND

Cyanotic congenital heart disease (CHD) accounts for 20% of all cardiac malformations with an estimated incidence of 2.5–3 per 1,000 live births. An increasing number of patients now survive into adolescence, with or without intervention, forming a unique group requiring specialized care.

To determine factors influencing survival among adolescents with unrepaired cyanotic CHD.

This single-center case-control study was conducted from 2017 to 2022 in a specialized tertiary center in the Philippines. Sample size was based on a 2.6% total fatality rate among infants who underwent CHD operations. Binary logistic regression was used to identify significant predictors of survival, with pRESULTS

Among 125 subjects, 58% (72/125) were males with a median age of 16 years. The median age at diagnosis was 1 year and 1 month; 73% resided outside Metro Manila. Most patients were New York Heart Association (NYHA) Class I (49%), with Tetralogy of Fallot as the most common diagnosis (52%) and 26% had palliative procedures. Predictors of survival included place of origin (OR 0.38, 95% CI 0.15–0.95, p = 0.039), oxygen saturation (OR 1.12, 95% CI 1.06–1.17, pCONCLUSION

Optimizing oxygenation, improving access to care and strengthening targeted interventions are crucial for enhancing survival among adolescents with unrepaired cyanotic CHD.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

Humans ; Heart Defects, Congenital/diagnosis* ; Genetic Testing/standards* ; Child ; Consensus ; China

Humans ; Heart Defects, Congenital/therapy* ; Child ; Evidence-Based Medicine ; Cardiac Surgical Procedures/methods* ; Cardiac Catheterization/methods*