Search Results (277)

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

(1) Background: Human Papillomavirus (HPV)-associated oropharyngeal cancer is the fastest-growing head and neck malignancy, yet vaccination coverage remains suboptimal. (2) Methods: In this cross-sectional survey conducted from April 2022 to April 2023, 400 parents of patients aged 8–18 years (mean ± SD = 12.8 ± 2.6; 59.3% female) reported their child’s HPV vaccination status and willingness to initiate or complete the vaccine series at a dental clinic. For those who were not fully vaccinated, reasons for refusal were documented. (3) Results: Over half (54.5%, n = 218) of the children were not fully vaccinated. Notably, 21% (46/218) of parents indicated an immediate willingness to vaccinate their child if the dentist offered it—a significant potential for improvement compared to general healthcare settings. Reported barriers included preference for a physician’s office (43.6%), indecision (20.3%), unspecified concerns (14.5%), safety worries (8.1%), and religious objections (5.2%). Male and younger patients (9–11 years) showed significantly lower vaccination coverage (p < 0.05). (4) Conclusions: Dentists can substantially impact public health by integrating immunization counseling, interprofessional collaboration, and vaccine administration, thereby addressing critical gaps in HPV-related cancer prevention. These findings highlight the opportunity for dental offices to enhance vaccination rates and prompt further research, education, and policy initiatives to advance the oral and general health of our patients. Full article

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, often fatal congenital disorder characterized by severe neonatal respiratory distress and associated with complex multisystem malformations. In approximately 90% of cases, the condition is linked to deletions or mutations affecting the FOXF1 gene or its upstream enhancer region on chromosome 16q24.1. This review analyzes reported prenatal cases with 16q24.1 deletion involving FOXF1, aiming to identify recurrent sonographic features and elucidate the underlying genomic and epigenetic mechanisms. We reviewed prenatal cases reported in the literature involving deletions of the 16q24.1 region, including the FOXF1 gene. Here, we expand the case series by reporting a fetus with increased nuchal translucency measuring 8 mm and a de novo 16q24.1 deletion. We identified nine prenatal cases with a 16q24.1 deletion, all involving the FOXF1 gene or its enhancer region. The main ultrasound findings included increased nuchal translucency and cystic hygroma during the first trimester, and cardiac, renal, and intestinal malformations from 20 weeks of gestation onward. Prenatal diagnosis of ACDMPV based solely on ultrasound findings is challenging. In most reported cases, the pregnancy was carried to term, with the diagnosis being confirmed by post-mortem histopathological examination. In the only case in which the pregnancy was terminated at 14 weeks’ gestation, histological examination of the fetal lungs, despite them being in the early stages of development, revealed misaligned pulmonary veins in close proximity to the pulmonary arteries and bronchioles. Evidence highlights the significance of non-coding regulatory regions in the regulation of FOXF1 expression. Differential methylation patterns, and possible contributions of parental imprinting, highlight the complexity of FOXF1 regulation. Early detection through array comparative genomic hybridization (array CGH) or next-generation sequencing to identify point mutations in the FOXF1 gene, combined with increased awareness of ultrasound markers suggestive of the condition, could improve the accuracy of prenatal diagnosis and genetic counseling. Further research into the epigenetic regulation of FOXF1 is crucial for refining recurrence risk estimates and improving genetic counseling practices. Full article

Background and Objectives: The transition from pediatric to adult-oriented healthcare is challenging and data on parental involvement and perception regarding the transition of children with chronic digestive diseases are scarce. Materials and Methods: Legal guardians of adolescents with chronic digestive diseases receiving care at a North-Eastern Romanian tertiary center and private offices were administered a 30-item survey. Results: There were 124 responders; 73.4% lived in rural areas; 81.5% were patients’ mothers. Positive correlations were found between parents’ perception of the child’s readiness for health-related decisions and appreciation of the children’s preparedness for transition (0.544; p = 0.000), between parents encouraging their children to maintain healthcare records and their perception of the children’s knowledge about their disease (0.67; p = 0.000), between parents’ fear of therapeutic breaks during transition and their perception of the need for transition training (0.704; p = 0.000), between fears for children’s impropriate health-related choices, fears of therapeutic breaks (0.573; p = 0.00) and parental perception that the adult physicians would be more patient-oriented and less family-centered (0.453; p < 0.000) and between parents’ trust in their children’s self-management skills and encouraging them to make decisions on their own (0.673; p < 0.000). Conclusions: The results of our study highlight the importance of addressing parental fears during special parent–children counseling sessions and promoting a child’s independence, chronic disease knowledge, records and alone consultations. Full article

School social work practice in the South African context is a growing field; however, there is limited research regarding the roles and responsibilities of school social workers, particularly in the Gauteng province. This province is unique in that school social workers are employed by multiple institutions, including individual schools and the education and social development departments. This study aimed to explore and describe the roles and responsibilities of school social workers in the Gauteng province, recognizing them as critical specialists in addressing learners’ psychosocial needs within school settings. An explorative qualitative design was used in this study. Data were collected from 22 purposively selected participants, comprising school social workers, supervisors, and provincial managers of school social work programs. Semi-structured interviews were conducted to collect data, and thematic analysis was employed to identify themes. The findings revealed context-specific roles of school social workers, including the creation of conducive teaching and learning environments, advocacy for social justice and child protection, conducting interviews and psychosocial assessments, providing counseling and trauma debriefing, conducting home visits and offering family services, removing abused learners from harmful environments, including their respective homes, and providing parental skills training and support. As a conclusion, this study highlights the need for standardized national and provincial guidelines to formalize and support school social work practice. It is recommended that the identified roles be incorporated into future practice frameworks. Furthermore, it is suggested that a uniform assessment tool be developed to promote consistency and guide school social workers in the initial evaluation processes. Full article

Introduction: Fraser syndrome (FS) is a rare autosomal recessive disorder. However, the clinical presentation remains variable. Diagnosis is based on a series of major and minor clinical criteria that can be supported by genetic tests. Prenatal diagnosis remains challenging. Methods: Herein, we reported a case of Fraser syndrome that was missed by ultrasound and diagnosed late at birth. The newborn presented with cryptophthalmos–syndactyly syndrome and absence of the right kidney. Based on a literature review of articles from the past 20 years, the authors found 40 cases, including indexed cases on PUBMED, Scopus, Web of Science, and Scholar using keywords related to “Fraser syndrome”. Through this report, we discuss the polymalformative syndrome, the clinical and paraclinical aspects of this syndrome, its clinical management, and highlight the importance of prenatal diagnosis in the light of research. Results: Our study found that consanguine parents (41.0%) were increasing risk factors for FS and poor socio-economic status delayed the early detection of FS. Among the 40 cases, 27 cases were detected postnatally. More than half of the cases resulted in poor perinatal outcomes. The common findings were cryptophthalmos (87.5%), syndactyly (87.5%), renal abnormalities (55.5%), and genital abnormalities (42.5%). Conclusions: A prenatal diagnosis of Fraser syndrome is still difficult. Thus, a counseled ultrasound scan at a specialized center should be recommended in suspected cases with indirect signs and risk factors of consanguinity. Full article

Unilateral renal agenesis (URA) is a urinary tract congenital anomaly characterized by a congenital absence or early developmental arrest of only one kidney. In the presence of a normal contralateral kidney, URA is typically considered a condition of minimal clinical significance as the solitary kidney often undergoes hypertrophy and can sufficiently perform the needed renal function after birth. However, postnatal studies suggest that URA has a significant association with other urinary and extra-urinary anomalies and may have implications for long-term health. This descriptive review focuses on the perinatal aspects of URA, emphasizing the main ultrasound findings to establish the prenatal diagnosis and to guide perinatal management. The pediatric implications of this diagnosis, particularly the high prevalence of long-term complications including hypertension, proteinuria, and a decreased glomerular filtration rate, are also briefly reviewed. URA is consistently associated with other ipsilateral urogenital anomalies. In females, there is a significant association with uterine anomalies that has significant implications for subsequent reproductive function. In males, the prevalence of both urinary and genital anomalies is also increased, which may also have implications for future fertility. Prenatal ultrasound offers the possibility of early diagnosis and parental counseling, which may result in timely intervention to reduce contralateral renal damage, prevent severe urogenital manifestations and co-morbidities, and improve fertility and the quality of life. Full article

Meckel–Gruber syndrome (MKS) is a rare autosomal recessive lethal ciliopathy, characterized by occipital encephalocele, cystic kidneys, and postaxial polydactyly, caused by mutations in different genes. Its significant genetic heterogeneity along with its clinical overlap with other ciliopathies makes early diagnosis essential for clinical management, accurate genetic counseling, and informing future reproductive decisions. Objectives: This study aims to describe a prenatally diagnosed case carrying a homozygous B9D1 variant and to examine the current literature on all variants reported in this gene associated with MKS. Methods: We comprehensively review the current literature on pathogenic B9D1 variants implicated in this syndrome. Additionally, we describe a case, presenting multiple congenital anomalies suggestive of MKS, genetically diagnosed by clinical exome sequencing on chorionic villi. Results: Occipital encephalocele and polycystic kidneys were revealed via ultrasound, thus suggesting MKS. Genetic testing identified the homozygous c.151T>C (p.Ser51Pro) variant in the B9D1 gene, inherited from healthy parents. Conclusions: This case supports the pathogenicity of the homozygous B9D1 c.151T>C variant and underscores the importance of timely prenatal assessment and targeted genetic testing for the detection of MKS risk in heterozygous subjects, enabling appropriate pregnancy management and informed reproductive choices. Full article

Background and Clinical Significance: Proximal femoral focal deficiency (PFFD), also referred to as congenital femoral deficiency, is a longitudinal limb deficiency and birth defect that affects the lower extremity including the hip and femur, resulting in a deformed and shortened limb. It can be diagnosed and classified using a combination of imaging modalities, including radiographs, ultrasonography, magnetic resonance imaging and computerized tomography. It is crucial to characterize this birth defect in the prenatal period to appropriately prepare parents through counseling. Postnatal imaging should be performed to confirm the diagnosis, prognosticate and predict the patient’s course for treatment and management. Close follow-up and family/patient-centered care contribute to optimized patient outcomes. Case Presentation: Here, we present a series of three cases of varying PFFD severity and presentation, detailing the evaluation process, the limitations and value of imaging, and the treatment outcomes of these patients. Each case has a different PFFD classification and treatment strategy that we utilized according to the data that we attained through continuous patient care and discussion. Conclusions: We highlight the difficulties in identifying and classifying PFFD in the prenatal period while demonstrating how postnatal imaging clarified the diagnosis and informed appropriate counseling and treatment. Close follow-up and the length of patient continuity allowed us to maximize patient outcomes despite the variety in PFFD presentation and severity. Full article

Background/Objective: The accurate diagnosis of congenital central nervous system abnormalities is critical to pre- and postnatal prognostication and management. When an abnormality is found in the posterior fossa of the fetal brain, parental counseling is challenging because of the wide spectrum of clinical and neurodevelopmental outcomes in patients with Dandy–Walker (DW) spectrum posterior malformations. The objective of this study was to evaluate the utility of biometric measurements obtained from fetal magnetic resonance imaging (MRI) to facilitate the prenatal differentiation of Dandy–Walker (DW) spectrum malformations, including vermian hypoplasia (VH), Blake’s pouch cyst (BPC), and classic Dandy–Walker malformation (DWM). Methods: This retrospective single-center study evaluated 34 maternal–infant dyads referred for fetal MRI evaluation of suspected DW spectrum malformations identified on antenatal ultrasound. Radiologists took posterior fossa measurements, including the vermis anteroposterior (AP) diameter, vermis height (VH), and tegmento–vermian angle (TVA). The posterior fossa, fourth ventricle, and cisterna magna were classified as normal, large, or dilated. The postnatal imaging findings were evaluated for concordance. The acquired values were compared between the groups and with normative data. The genetic testing results are reported when available. Results: A total of 27 DW spectrum fetal MRI cases were identified, including 7 classic DWMs, 14 VHs, and 6 BPCs. The TVA was significantly higher in the DWM group compared with the VH and BPC groups (p < 0.001). All three groups had reduced AP vermis measurements for gestational age compared with normal fetal brains, as well as differences in the means across the groups (p = 0.002). Conclusions: Biometric measurements derived from fetal MRI can effectively facilitate the prenatal differentiation of VH, BPC, and classic DWM when assessing DW spectrum posterior fossa lesions. Standardizing biometric measurements may increase the diagnostic utility of fetal MRI and facilitate improved antenatal counseling and clinical decision-making. Full article

Background: Children and adolescents with pediatric inflammatory bowel diseases (PIBD) face significant challenges, including emotional stress, social isolation, and interrupted education due to symptoms. Effective counseling and education empower these young patients and their families to actively participate in healthcare. This paper investigates the IBD needs analysis (CEDNA), focusing on counseling and transition services. Methods: The Study Group distributed questionnaires to PIBD patients and the parents of children and adolescents with PIBD across Germany, with all responses provided anonymously. We conducted a subgroup analysis based on patient age and time since diagnosis, as well as aspects of regional distribution and city size. Parents’ responses were analyzed by corresponding age groups to facilitate comparison with the patients’ responses. Results: From October 2021 to April 2022, 1158 questionnaires (patients 38.9%, n = 450; parents 61.1%, n = 708) were completed. In the group of 16–17-year-old patients, only 14.1% (n = 239) feel well informed about transition programs (parents 6.7% of n = 360). Depending on the disease duration, 2.1% to 6.9% of the patients surveyed (n = 292) feel well informed about PIBD (parents 3.3% to 7.5%, n = 361). Nutritional counseling is the most requested support service (patients 49.2%, n = 382; parents: service used for their children 41.9%, n = 578; parents: service used for themselves 46.1%, n = 575). Conclusions: PIBD patients, especially aged 12–17, lack knowledge and preparation for transition to adult care. While general PIBD management awareness is fair, targeted educational efforts are necessary. Trustworthy information sources and early, tailored counseling services could enhance transition experiences and improve long-term disease management and patient outcomes. Full article

Newborn Bloodspot Screening (NBS) can detect severe treatable health conditions with onset during infancy. The parents of a newborn baby are vulnerable in the days after birth, and the optimal way to deliver the shocking and distressing news of a potential serious diagnosis is yet to be defined. More data are needed to determine whether access to a genetic counsellor (GC) improves families’ experiences with genetic conditions identified by NBS. This study aimed to explore the similarities and differences for parents who received a positive NBS result for Spinal Muscular Atrophy (SMA) and received access to a GC (GC cohort), to a cohort of parents who received a diagnosis for inborn errors of metabolism (IEM) and did not have access to a GC (non-GC cohort). Semi-structured interviews explored the retrospective experiences of receiving the NBS result, including diagnosis implications and subsequent adaptation to respective genetic diagnoses. Inductive thematic analysis was used from group comparison. 7 SMA families and 5 IEM families were included in the study. Four themes were identified: 1. minimal pre-test counselling; 2. perceived lack of local healthcare team knowledge; 3. enabling factors for adaptation; 4. implications for both individuals and their families. Both the GC and non-GC cohorts reported insufficient counselling in the pre-test period and described feeling traumatised at the time of the diagnosis delivery. Families without subsequent GC input described limited understanding of the disease due to the use of medicalized terms, as well as a decreased understanding of reproductive options, familial communication and subsequent cascade screening. GCs can support information needs and adaptation following a NBS diagnosis. Full article

Background: Cochlear implants (CIs) have become a widely used intervention for Deaf and hard-of-hearing (DHH) children, particularly for developing spoken language. However, parental decision-making regarding CIs is influenced by a range of factors, including socio-economic status, healthcare accessibility, cultural beliefs, and societal attitudes. While extensive research on parental perceptions of CIs exists in high-income countries (HICs), there is limited research on these perspectives in low- and middle-income countries (LMICs), like South Africa, where disparities in healthcare access significantly impact CI uptake. Objectives: This study aimed to explore the views and perceptions of South African parents regarding CIs for their DHH children, with a specific focus on how financial, cultural, and informational barriers influence decision-making. Methods: A mixed-methods approach was used, combining Q-methodology for quantitative data and thematic analysis for qualitative insights. Nine parents of DHH children participated. The Q-set survey ranked parental attitudes toward CI risks, benefits, and accessibility, while semi-structured interviews provided deeper insights into decision-making processes. Factor analysis grouped participants into clusters based on their perceptions, and qualitative data were analysed using a thematic framework approach. Results: Findings revealed two distinct parental clusters: (a) Cluster 1 parents viewed CIs as essential for speech development and strongly supported implantation, and (b) Cluster 2 parents recognized CI benefits but emphasized that outcomes vary based on individual circumstances. Three overarching themes emerged from thematic analysis: (1) financial barriers restricting CI access, (2) parental reliance on medical professionals for decision-making, and (3) persistent stigma and cultural beliefs influencing CI perceptions. Conclusions: This study highlights critical barriers to CI access in South Africa, including socio-economic inequities, limited healthcare infrastructure, and persistent stigma. While parents largely recognized the benefits of CIs, their decisions were shaped by financial constraints and concerns about Deaf identity and societal acceptance. This study calls for the expansion of publicly funded CI programmes, the development of culturally tailored parental counselling protocols, and targeted public awareness campaigns to reduce stigma surrounding hearing restoration devices. These interventions can help mitigate financial and cultural barriers to CI adoption in South Africa. Full article

India’s population complexity presents varied challenges in genetic research, and while facilities have gained traction in tier-1 and -2 cities, reliance on international collaborations often delays such investigations. COVID-19 further exacerbated the issues with such sample sharing. Congenital Hyperinsulinism (CHI) is a rare genetic disorder of pancreatic β-cells causing hypoglycaemia in children due to abnormal insulin secretion. Given India’s high birth rate and consanguineous populations, annual CHI cases are estimated to be around up to 10,000, with up to 50% having unexplained genetic causes. Diffuse or atypical lesions in such patients often necessitate near-total-pancreatectomy, risking pancreatic exocrine insufficiency and diabetes, requiring lifelong therapy. Also, novel genetic variations complicate accurate diagnosis, risk assessment, and counselling, emphasising the need for rapid genetic assessment to prevent neurological injuries and inform treatment decisions. Despite significant efforts at many institutes, there are no dedicated organisations for CHI in India. With the implementation of the National Policy for Rare Diseases 2021, we plan to form a non-profit organisation, “Congenital Hyperinsulinism India Association (CHIA)”, comprising paediatric endocrinologists, paediatricians, geneticists, and independent researchers. The aims of this association are to generate a national database registry of patients, formulate a parent support group and CHIA consortium, design patient information leaflets, as well as foster genomic collaborations and promote clinical trials. Such steps will help sensitise the health authorities and policy makers, urging them to improve the allocation of health budgets for rare diseases, as well as empower patients and their families, contributing towards a better quality of life. Full article

Haemoglobinopathies are among the most prevalent genetic disorders globally. In the context of these conditions, preimplantation genetic testing (PGT) plays a pivotal role in preventing genetic diseases in the offspring of carrier parents, reducing the need for pregnancy termination and enabling the selection of compatible sibling donors for potential stem cell transplantation in cases of thalassemia or sickle cell disease. This review explores the evolving role of PGT as a reproductive option for haemoglobinopathy carriers, tracing the development of PGT protocols from patient-specific to comprehensive testing enabled by advanced technologies like next-generation sequencing (NGS). We discuss key technical, biological, and practical limitations of PGT, as well as the ethical considerations specific to haemoglobinopathies, such as the complexity of interpreting genotypes. Emerging technologies, such as whole-genome sequencing, non-invasive PGT, and gene editing, hold significant promise for expanding applications but also raise new challenges that must be addressed. It will be interesting to explore how advancements in technology, along with the changing management of haemoglobinopathies, will impact reproductive choices. It is anticipated that continued research will improve genetic counseling for PGT for haemoglobinopathies, while a careful evaluation of ethical and societal implications is also required. Responsible and equitable implementation of PGT is essential for ensuring that all families at risk can make informed reproductive choices. Full article