Congenital Anomalies最新文献

X-linked cardiac valvular dysplasia (XCVD) has been associated with missense or in-frame deletion variants in FLNA. We report a Japanese family with cardiac valvular dysplasia. The proband was diagnosed with multiple valve dysplasia at a primary school health checkup. He also exhibited skin hyperextensibility and joint hypermobility. His younger monozygotic twin brothers were diagnosed with multiple valve dysplasia during their 1-month pediatric checkups. One of them exhibited severe valvular disease and required aortic and mitral valve replacement at age 16 due to progressive regurgitation. All three patients showed no developmental delay or evidence of periventricular nodular heterotopia on brain MRI. We identified a novel hemizygous FLNA variant, NM_001456.4(FLNA):c.2023-6_2026delinsACGCT, in all three patients. Splicing analysis revealed an in-frame deletion of two amino acids, p.Val675_Lys676del. No significant difference was observed in overall expression levels of FLNA transcript between the patient and a healthy individual. In silico structural modeling revealed that this deletion disrupts an α-helix positioned between β-strands of domains 4 and 5, which would impair the structural stability of FLNA. This variant was not found in public genomic databases. In conclusion, we identified a novel likely pathogenic variant in FLNA, p.Val675_Lys676del, the smallest in-frame deletion reported to date in XCVD. Patients with this variant showed variable severity, and some presented with extracardiac features. Our findings expand both the genetic and phenotypic spectrum of XCVD.

We report the case of a 3-year-old girl with alpha-thalassemia/mental retardation linked to chromosome 16 (ATR-16) syndrome. The patient presented with hypotonia, developmental delay, and characteristic facial features including hypertelorism and a broad nasal bridge. Blood test results indicated microcytic anemia and normal iron status, suggestive of thalassemia. Genetic analysis revealed that the patient harbored a 465 kb deletion in the 16p13.3 region and a 19.4 Mb duplication in the 16q22.1–q24.3 region. The patient presented with rare complications of ATR-16 syndrome, including anal fistula, vesicoureteral reflux (VUR), and patent ductus arteriosus (PDA). Comparison of this case with previously reported patients with pure partial trisomy 16q suggested that the duplicated distal 16q region may be a critical locus associated with VUR and PDA.

The three-dimensional structural distribution of lens fiber cells, which form an elaborate lens during the late embryonic and early fetal periods (first trimester), remains unresolved. Therefore, this study aimed to assess the sequential three-dimensional morphology, morphometry, and inner structure of human embryonic (N = 10) and fetal (N = 27) lenses in the first trimester using magnetic resonance imaging and tractography. The T1-weighted magnetic resonance imaging intensity and fractional anisotropy values were high at the embryonic lens, where at least two layers, the inner and outer layers, became distinguishable during the late embryonic period (Carnegie stage 21–23) and the subsequent early fetal period. A comparison with histological findings indicated that the unique spherically oriented eigenvectors in the lens correspond to the lens fiber cell orientations. Furthermore, tractography demonstrated that the eigenvectors were oriented concentrically from the anterior to the posterior pole. Conversely, the eigenvectors around the centroid of the coronal section were irregular and exhibited low fractional anisotropy. Three-dimensional reconstructions, morphometry, and tractography revealed no apparent quadrant-specific deviations, as determined by the z-axis (anterior–posterior axis, AP axis), either morphologically or structurally, throughout the observation period. During the embryonic and early fetal periods, human lens cells may exhibit an exquisite hyperbolic arrangement. The ratio of transverse-to-AP length was < 1 in the late embryonic period when the lens cavity was obliterated. This ratio decreased linearly from approximately 0.9 to 0.7 as the crown-rump length increased. The three-dimensional morphometry of the lens remained unaffected, irrespective of its histological structure.

Type II Mayer–Rokitansky–Küster–Hauser (MRKH), also known as MURCS association (Müllerian agenesis, renal agenesis, and cervicothoracic somite anomalies), frequently presents with additional vertebral, renal, auditory, and skeletal anomalies. Due to its rarity and heterogeneous presentation, diagnosis and management remain challenging. This study aimed to contribute a new case of MURCS syndrome and systematically review the literature to assess the spectrum and prevalence of associated vertebral anomalies. We present the case of a 35-year-old woman with chronic neck pain and primary amenorrhea. Imaging revealed vertebral segmentation anomalies, Sprengel's deformity, omovertebral bone, scoliosis, and absence of the uterus and left kidney. Genetic testing confirmed a 46,XX karyotype. Multidisciplinary management was initiated with conservative treatment and specialist follow-up. A systematic literature review following PRISMA guidelines included 40 studies, encompassing 41 patients with MURCS syndrome. The mean age was 20.5 ± 11.2 years, and 87.8% were female. Common presenting symptoms were amenorrhea (41.5%), infertility (17.1%), and neck pain (12.2%). Physical findings included short neck (53.7%), short stature (53.7%), scoliosis (22%), Sprengel's deformity (19.5%), and facial asymmetry (31.7%). Cervical vertebral fusion was the most prevalent anomaly (53.7%), with frequent involvement of levels C2–C3 and C5–C6. This study highlights the underrecognized spectrum of vertebral anomalies in MURCS syndrome. Our case underscores the importance of multidisciplinary evaluation in patients with Müllerian agenesis and musculoskeletal complaints. Standardized reporting and further research are needed to better understand the clinical implications of skeletal anomalies in MURCS syndrome.

Congenital anomalies (CAs) are significant contributors to infant morbidity and mortality globally. In Vietnam, disparities in healthcare access, particularly in remote regions like Ben Tre Province, necessitate detailed research on CAs to inform public health strategies. This cross-sectional, retrospective study analyzed CAs among 126 233 live births at Nguyen Dinh Chieu Hospital in Ben Tre Province from 2008 to 2023. Data were collected using 33 diagnostic markers, with cases identified through physical examinations and ICD-10 classification. Cleft lip and palate emerged as the most common CAs, with a significant presence among the identified cases. The overall incidence of CAs throughout the study period was 0.342%. The annual incidence varied over time, declining from 0.736% in 2008 to 0.491% in 2023. Hand polydactyly and cleft lip were also frequently observed, while rare anomalies included facial clefts and conjoined twins. The study indicates a general decrease in CAs over 16 years, with cleft lip and palate showing the highest incidence. To address these anomalies effectively, improvements in prenatal care, diagnostics, and targeted interventions are essential. Future research should focus on specific risk factors and evaluate preventive measures, with continued monitoring critical for understanding trends and enhancing health outcomes.