Congenital Contractures and Fractures: A Variant of Bruck Syndrome Type 2.

Bruck syndrome, an exceptionally rare autosomal recessive disorder, manifests as bone fragility and congenital joint contractures. This syndrome is recognized as a fusion of arthrogryposis multiplex congenita and osteogenesis imperfecta and is categorized into Types 1 and 2. Bruck syndrome Type 2 stems from a homozygous mutation in the PLOD2 gene and exhibits characteristics such as osteopenia, congenital contractures with pterygia, femoral bowing, club feet, postnatal shorty stature, severe limb deformity, and progressive scoliosis. In this report, we describe the case of an infant presenting with multiple joint contractures of the distal extremities, bilateral talipes equinovarus deformity, and a history of a right femur fracture at birth, managed through closed reduction and plaster of Paris. The current treatment regimen includes physiotherapy, wrist splinting for wrist extension and thumb abduction, and serial casting of both lower limbs.

Pachyonychia congenita: A father and son with a novel variant in the KRT16 gene.

This study underscores the significance of identifying the clinical manifestations of pachyonychia congenita (PC) and emphasizes the patterns of genetic inheritance. A 12-month-old boy presented with a "white hairy tongue" and, following a comprehensive evaluation, was diagnosed with PC. His father exhibited similar symptoms. Genetic testing revealed a KRT16 pathogenic variant (c.616 T > G) in both the patient and his father, marking it as a novel variant in the PC literature. This case contributes to a broader understanding of PC's genetic diversity and its clinical presentations.

Expansion of the phenotypic spectrum of KARS1-related disorders to include arthrogryposis multiplex congenita and summary of experiences with lysine supplementation.

There are currently multiple disorders of aminoacyl-tRNA synthetases described, including KARS1-related disorder resulting from dysfunctional lysyl-tRNA synthetases. In this report, we describe four novel KARS1 variants in three affected individuals, two of whom displayed arthrogryposis-like phenotypes, suggestive of phenotypic expansion. We also highlight subjective clinical improvement in one subject following lysine supplementation in conjunction with a protein-fortified diet, suggesting its potential as a novel treatment modality for KARS1-related disorders. This report offers additional insight into the etiology and management of KARS1-related disorders and expands our ability to provide guidance to affected individuals and their families.

Congenital diaphragmatic hernia: relationship between defect size and outcome. Experience in a reference centre.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) remains a therapeutic challenge. The surgical classification recommended by the Congenital Diaphragmatic Hernia study group (CDHSG), based on the size of the defect, is used for staging in reference centres. Larger defects are associated with poorer outcomes. Our aim was to describe and compare the morbidity at hospital discharge of newborns who underwent surgical correction of CDH at the Juan P. Garrahan, according to the surgical staging of the defect proposed by the CDHSG. MATERIAL AND METHODS: The study included patients with CDH admitted to the Juan P. Garrahan Hospital between 2012 and 2020, and we analysed the distribution, morbidity and mortality associated with the size of the defect. We carried out a descriptive analysis, calculating measures of central tendency and dispersion, and bivariate and multivariate analyses. RESULTS: A total of 230 patients with CDH were admitted and 158 underwent surgery. We found that defect sizes C and D sizes were associated with an increased risk of chronic pulmonary disease (CPD) (OR, 5.3; 95% CI, 2.2-13.4; P<.0000), need of extracorporeal membrane oxygenation (OR 3.9; 95% CI, 1.3-12.8; P<.005) and chylothorax (OR, 2.1; 95% CI, 0.8-6.4; P<.10]. The multivariate analysis revealed that a large defect size (C-D) was independently and significantly associated with CPD (OR 4.19; 95% CI, 1.76-9.95). CONCLUSION: Staging the defect according to de CDHSG classification during surgery allows the application of uniform management criteria and the prediction of patient outcomes and complications during the hospital stay.

Early Diagnosis and Management of Arthrogryposis Multiplex Congenita in a Neonate: A Case Study.

Arthrogryposis multiplex congenita (AMC) is a rare condition characterized by multiple joint contractures at birth, affecting two or more body areas. The clinical examination revealed physical abnormalities indicative of AMC, including joint contractures, clubfeet, and scoliosis. The diagnostic evaluation confirmed the clinical suspicion, and prompt management was initiated to address respiratory distress and potential sepsis. Early diagnosis and multidisciplinary care are essential for optimizing outcomes in neonates with AMC. We present the case of a one-day-old neonate who exhibited immediate respiratory distress upon birth and was born via a lower segment cesarean section (LSCS) to a 31-year-old mother. This case underscores the importance of recognizing prenatal ultrasound findings suggestive of AMC and implementing appropriate postnatal care strategies for affected neonates. Early diagnosis and multidisciplinary care are essential for optimizing outcomes in neonates with AMC.

[Safety and efficacy of a therapeutic exercise program in young adults with repaired congenital diaphragmatic hernia]. / Seguridad y eficacia de un programa de ejercicio terapéutico en jóvenes intervenidos de hernia diafragmática congénita.

INTRODUCTION AND OBJECTIVE: Patients with congenital diaphragmatic hernia (CDH) can have up to 40 times more frequency of muskuloskeletal deformities and decreased perception of physical activity tan their pairs. The objective of this study is to evaluate the safety and efficacy of an individualized exercise program in late adolescents and young adults with repaired CDH, as well as a description of their basal status. MATERIAL AND METHODS: Non randomized prospective trial of 13 patients with repaired CDH between 1997-2005. An initial physical exploration and a pre-post assessment of bioimpedance (BIA), dynamometry, maximal inspiratory and expiratory pressure (MIP/MEP), 6-minute walk test (6MWT), physical activity level (IPAQ) and quality of life (QoL) was made. The training program last for 4 weeks. For the statistical analysis, the Student's t test for paired samples and Wilcoxon test were used. RESULTS: 77% (n=10) were male with a mean age of 19.23±2.13 years. In baseline BIA, 62% (n=8) had truncal sarcopenia that improved in -0.43±0.58, and P=.016. MIP, MEP, 6MWT and QoL tests increased by -7.27±8.26 cmH2O, P=.008; -11.91±10.20 cmH2O, P=.002; -70.63±17.88 m, P=.001; -42,19±26.79, P=.00 respectively. The IPAQ did not change significantly (P=0.86), however the time dedicated to muscle strengthening increased. No adverse effects were reported. CONCLUSIONS: A personalized rehabilitation program is safe and could improve the respiratory muscle strength and truncal sarcopenia as well as the submaximal effort capacity in late adolescents and young adults with repaired CDH.

Dyskeratosis congenita associated with a novel missense variant in TERT: Approach for the dermatologists.

Dyskeratosis congenita (DC) is a telomeropathy presenting diagnostic and therapeutic challenges across multiple specialties; yet, subtle dermatological signs enable early detection, altering patient prognosis. A specific DC genetic sequencing was performed according to the clinical criteria of our patient in study. Subsequently, cross-checked information in the main genetic databases was carried out. Additionally, an extensive review of the literature was made to organize the main dermatological aspects in DC. We report a novel variant of DC. Additionally, we share 10 useful and practical messages for dermatologists and any specialist caring for this group of patients.

Myotonia congenita in a Greek cohort: Genotype spectrum and impact of the CLCN1:c.501C > G variant as a genetic modifier.

INTRODUCTION/AIMS: Myotonia congenita (MC) is the most common hereditary channelopathy in humans. Characterized by muscle stiffness, MC may be transmitted as either an autosomal dominant (Thomsen) or a recessive (Becker) disorder. MC is caused by variants in the voltage-gated chloride channel 1 (CLCN1) gene, important for the normal repolarization of the muscle action potential. More than 250 disease-causing variants in the CLCN1 gene have been reported. This study provides an MC genotype-phenotype spectrum in a large cohort of Greek patients and focuses on novel variants and disease epidemiology, including additional insights for the variant CLCN1:c.501C > G. METHODS: Sanger sequencing for the entire coding region of the CLCN1 gene was performed. Targeted segregation analysis of likely candidate variants in additional family members was performed. Variant classification was based on American College of Medical Genetics (ACMG) guidelines. RESULTS: Sixty-one patients from 47 unrelated families were identified, consisting of 51 probands with Becker MC (84%) and 10 with Thomsen MC (16%). Among the different variants detected, 11 were novel and 16 were previously reported. The three most prevalent variants were c.501C > G, c.2680C > T, and c.1649C > G. Additionally, c.501C > G was detected in seven Becker cases in-cis with the c.1649C > G. DISCUSSION: The large number of patients in whom a diagnosis was established allowed the characterization of genotype-phenotype correlations with respect to both previously reported and novel findings. For the c.501C > G (p.Phe167Leu) variant a likely nonpathogenic property is suggested, as it only seems to act as an aggravating modifying factor in cases in which a pathogenic variant triggers phenotypic expression.

Clinical and molecular characterization of myotonia congenita using whole-exome sequencing in Egyptian patients.

BACKGROUND: Myotonia Congenita (MC) is a rare disease classified into two major forms; Thomsen and Becker disease caused by mutations in the CLCN1 gene, which affects muscle excitability and encodes voltage-gated chloride channels (CLC-1). While, there are no data regarding the clinical and molecular characterization of myotonia in Egyptian patients. METHODS: Herein, we report seven Egyptian MC patients from six unrelated families. Following the clinical diagnosis, whole-exome sequencing (WES) was performed for genetic diagnosis. Various in silico prediction tools were utilized to interpret variant pathogenicity. The candidate variants were then validated using Sanger sequencing technique. RESULTS: In total, seven cases were recruited. The ages at the examination were ranged from eight months to nineteen years. Clinical manifestations included warm-up phenomenon, hand grip, and percussion myotonia. Electromyography was performed in all patients and revealed myotonic discharges. Molecular genetic analysis revealed five different variants. Of them, we identified two novel variants in the CLCN1 gene ( c.1583G > C; p.Gly528Ala and c.2203_2216del;p.Thr735ValfsTer57) and three known variants in the CLCN1 and SCN4A gene. According to in silico tools, the identified novel variants were predicted to have deleterious effects. CONCLUSIONS: As the first study to apply WES among Egyptian MC patients, our findings reported two novel heterozygous variants that expand the CLCN1 mutational spectrum for MC diagnosis. These results further confirm that genetic testing is essential for early diagnosis of MC, which affects follow-up treatment and prognostic assessment in clinical practice.

The experience of caregiving for children with rare musculoskeletal conditions: a qualitative study in arthrogryposis multiplex congenita.

BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a group of rare musculoskeletal conditions that is associated with complex healthcare needs and long-term follow up. The literature reports significant direct, indirect, and psychosocial costs for caregivers of children with neuromuscular conditions. Due to mobility limitations and frequent hospital visits, caring for a child with AMC is complex. Other challenges experienced by caregivers include financial strain, job changes, changes in interpersonal relationships and abandonment. This study was aimed at exploring the lived experience of caregivers of children with AMC. METHODS: The present study is part of a larger global mixed methods study. In the initial quantitative aspect of the study, caregivers (n = 158) of children and youths with AMC (aged 0-21 years) responded to a cost of care survey on an electronic platform. Of the 158 participants, 13 caregivers then further consented to participate in the qualitative aspect of the study in which a 60-min semi-structured, individual interview was conducted remotely. Open-ended questions were developed to gain a deeper understanding of the direct and indirect costs of care, their impact on the caregivers' lives and the quality of the care-giving experience. Interviews were transcribed, and a coding scheme was developed drawing from both the existing literature and the content of the interviews. A deductive and inductive thematic analysis was used to analyze the qualitative data using the NVivo® qualitative data analysis software. RESULTS AND CONCLUSION: Five themes describing the experiences of caregivers of children with AMC emerged from the analysis of the qualitative data: 1. Impact of the caregiving experience; 2. Cost of childcare; 3. Support system for care; 4. Managing and navigating care; 5. Supporting the child's growth and development. In addition to the results of the thematic analysis, specific recommendations shared by the caregivers included the need for support groups and provision of support to youths to prepare them for adolescence. These findings will inform resource allocation, policymaking, and support services for children with rare conditions, their caregivers and families.

Generalized cutis marmorata telangiectatica congenita or neonatal lupus? A case report and literature review.

Cutis marmorata telangiectatica congenita (CMTC) presents as marbled erythema and may exhibit diverse associated anomalies. Thorough multidisciplinary evaluation is crucial. Treatment varies with inconclusive evidence, necessitating further research. Our case underscores CMTC's rarity and heterogeneous nature, advocating for comprehensive management approaches and ongoing research.

Adverse cardiovascular, obstetric and perinatal events during pregnancy and puerperium in patients with heart disease.

BACKGROUND AND OBJECTIVES: cardiovascular changes during pregnancy carry greater risk in heart disease. We analyze cardiovascular, obstetric and perinatal adverse effects associated with congenital and acquired heart disease during pregnancy and postpartum. MATERIALS AND METHODS: Cross-sectional and retrospective study, which included the 2017-2023 registry of pregnant or postpartum patients hospitalised with diagnosis of congenital or acquired heart disease. Adverse events (heart failure, stroke, acute pulmonary edema, maternal death, obstetric haemorrhage, prematurity and perinatal death) were compared with the clinical variables and the implemented treatment. RESULTS: 112 patients with a median age of 28 years (range 15-44) were included. Short circuits predominated 28 (25%). Thirty-six patients (32%) were classified in class IV of the modified WHO scale for maternal cardiovascular risk. Heart failure occurred in 39 (34.8%), acute lung edema 12 (10.7%), stroke 2 (1.8%), maternal death 5 (4.5%), obstetric haemorrhage 4 (3.6%), prematurity 50 (44.5%) and perinatal death 6 (5.4%). Shunts were associated with prematurity (adjusted odds ratio 4; 95% CI: 1.5-10, p = 0.006). Peripartum cardiomyopathy represented higher risk of pulmonary edema (adjusted OR 34; 95% CI: 6-194, p = 0.001) and heart failure (adjusted OR 16; 95% CI: 3-84, p = 0.001). An increased risk of obstetric haemorrhage was observed in patients with prosthetic valves (adjusted OR 30; 95% CI: 1.5-616, p = 0.025) and with the use of acetylsalicylic acid (adjusted OR 14; 95% CI: 1.2-16, p = 0.030). Furthermore, the latter was associated with perinatal death (adjusted OR 9; 95% CI: 1.4-68, p = 0.021). CONCLUSIONS: severe complications were found during pregnancy and postpartum in patients with heart disease, which is why preconception evaluation and close surveillance are vital.

Cancer Precursor Syndromes and Their Detection in the Head and Neck.

This article explores the multifaceted landscape of oral cancer precursor syndromes. Hereditary disorders like dyskeratosis congenita and Fanconi anemia increase the risk of malignancy. Oral potentially malignant disorders, notably leukoplakia, are discussed as precursors influenced by genetic and immunologic facets. Molecular insights delve into genetic mutations, allelic imbalances, and immune modulation as key players in precancerous progression, suggesting potential therapeutic targets. The article navigates the controversial terrain of management strategies of leukoplakia, encompassing surgical resection, chemoprevention, and immune modulation, while emphasizing the ongoing challenges in developing effective, evidence-based preventive approaches.

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma.

Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient's 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.

Lessons to Learn About the Misdiagnosis of a Rare Case in China: Bart Syndrome or Carmi Syndrome?

Objective: We report a case of Carmi Syndrome in a neonate. Aim: To share our lessons in diagnosis of the case of Carmi Syndrome. Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth. Outcome: The neonate passed away about 30 hours after birth. Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.

Dyskeratosis congenita: a rare case report.

Dyskeratosis congenita (DKC) is a rare genetic disorder characterized by lacy reticular skin hyperpigmentation, bone marrow failure, nail dystrophy, and oral leukoplakia. To the best of our knowledge, only around 200 cases were reported in the medical literature, and in this report, we present another distinctive case from Syria. This case report describes a male patient with generalized reticular pigmentation and abnormal nails since childhood. The patient reported a history of recurrent urethral stenosis and corneal density. Dermoscopic examination revealed pigmented lines arranged in a netlike pattern. Histopathological findings were nonspecific. Hematological values were unremarkable. A contrast CT scan revealed changes in the bladder wall. The final diagnosis of Dyskeratosis Congenita was made based on the clinical criteria. This disorder can present with additional cutaneous manifestations and systemic complications. Treatment are generally prescribed to maintain bone marrow function, based on the fact that it is the major cause of death. Regular monitoring and screening for associated conditions are recommended.

Optical coherence tomography angiography in pediatric ocular cutis marmorata telangiectatica congenita: A case series.

Purpose: To report 2 cases of enlarged foveal avascular zone (FAZ) on optical coherence angiography (OCTA) imaging in pediatric patients with cutis marmorata telangiectatica congenita (CMTC). Observations: A 10-week-old female and a 3-year-old male diagnosed with CMTC presented for retinal examination. Both had peripheral avascularity on fluorescein angiography (FA) and enlargement of the FAZ on OCTA in both eyes. Conclusions and Importance: Pediatric patients with CMTC should undergo ocular evaluation with not only FA, but also OCTA to more robustly evaluate the affected retina in this rare disease.

An Unusual Presentation of Membranous Nephropathy in an Adult With Arthrogryposis: A Case Report.

Membranous nephropathy (MN) is an autoimmune condition that is a common cause of nephrotic syndrome in nondiabetic adults. In this study, we highlight a case of a 22-year-old male with a past medical history of arthrogryposis multiplex congenita (AMC) who initially presented with right flank pain and hematuria. Subsequent workup revealed significant proteinuria with biopsy-proven primary MN. Early detection of the disease is critical to establish treatment promptly and prevent complications such as those resulting from a hypercoagulable state.

X-linked Dyskeratosis Congenita Case with Mutation 1058C>T(p.Ala353Val) in Dyskerine Gene.

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome and telomere biology disorder, usullay consisting of a triad of oral leucoplakia, dystrophic nails, reticular skin pigmentation. The diagnosis in the majority of cases can be made following all the clinical findings of this triad are established. Here we report 7 years-old boy who had oral leukoplakia and nail abnormality without skin involvement, associated with bone marrow failure diagnosed with X-linked DC due to dyskerin (DKC1) mutation. Our report emphasizes the fact that clinical suspicion can prevent fatal consequences since all manifestations may not always be seen collectively.