Congenital Research Articles

Newborn with Refractory Seizures due to Hemimegalencephaly and Tuberous Sclerosis Complex: Case Report and Literature Review.

Hemimegalencephaly (HME) is a rare congenital disorder that is initiated during embryonic development with abnormal growth of one hemisphere. Tuberous sclerosis complex (TSC), a genetic disorder, is rarely associated with HME.We present a case of a newborn with HME with a confirmed mutation in the TSC-1 gene and describe the clinical course, findings on amplitude-integrated electroencephalography (aEEG), cranial ultrasound (CUS), MRI, and the postmortem evaluation. Furthermore, we conducted a comprehensive literature review of all reported newborns with HME and a genetically confirmed TSC mutation.This infant experienced therapy-resistant seizures after birth despite treatment with multiple antiseizure medications. CUS and MRI revealed HME of the left hemisphere. Early functional hemispherectomy, around the age of 3 months, was considered but dismissed after multidisciplinary evaluation, medical ethical consultation, and multiple discussions with the parents. Care was redirected due to worsening clinical and neurologic conditions, increasing respiratory insufficiency, and ongoing therapy-resistant seizures. Postmortem evaluation of the brain revealed hamartomatous brain changes and irregular gyration of the enlarged hemisphere. in addition, these changes were also present in the previously considered unaffected side, raising thoughts about the potential effectiveness of functional hemispherectomy.This case report illustrates that in cases with TSC abnormalities might not be confined solely to the initially considered affected side. This can have important therapeutic implications.

Pathogenic variants in SHROOM3 associated with hemifacial microsomia.

Hemifacial microsomia (HFM) is a rare congenital disorder that affects facial symmetry, ear development, and other congenital anomalies. However, known causal genes account for only approximately 6% of patients, indicating the need to discover more pathogenic genes. Association tests demonstrated an association between common variants in SHROOM3 and HFM (P = 1.02E-4 for the lead SNP), while gene burden analysis revealed a significant enrichment of rare variants in HFM patients compared to healthy controls (P = 2.78E-5). We then evaluated the expression patterns of SHROOM3 and the consequences of its deleterious variants. Our study identified 7 deleterious variants in SHROOM3 among the 320 Chinese HFM patients and 2 deleterious variants in two HFM trios, respectively, suggesting a model of dominant inheritance with incomplete penetrance. These variants were predicted to significantly impact SHROOM3 function. Furthermore, the gene expression pattern of SHROOM3 in the pharyngeal arches and the presence of facial abnormalities in gene-edited mice suggest that SHROOM3 plays important roles in facial development. Our findings suggest that SHROOM3 is a likely pathogenic gene for HFM.

Quando un deficit nutrizionale simula una displasia midollare

A 12-year-old patient with epilepsy, autism spectrum disorder and a selective diet presents with severe macrocytic anaemia and weight loss.Tests reveal deficiencies in vitamin B12 and folate, leading to a diagnosis of megaloblastic anaemia. Malnutrition related to the diet is suspected, and investigations are ongoing to rule out malabsorption or underlying congenital conditions Scuola di Specializzazione in Pediatria, UO di Oncoematologia Pediatrica, Azienda Ospedaliero-Universitaria Pisana

Late onset congenital central hypoventilation syndrome in a child with Down syndrome

Congenital central hypoventilation syndrome (CCHS), also known as Ondine syndrome, is a rare genetic disorder characterized by alveolar hypoventilation and dysregulation of the autonomic nervous system. Late onset congenital central hypoventilation syndrome (LOCCHS) has been infrequently reported, particularly in patients with Down syndrome. This case report presents an 8-year-old girl with Down syndrome who developed late onset CCHS. Clinical assessments, laboratory tests, and imaging studies were performed to evaluate her condition. The patient exhibited severe respiratory acidosis and hypoxemia, necessitating intubation and mechanical ventilation. Despite multiple extubation attempts, the patient demonstrated no spontaneous breathing. The diagnosis of LOCCHS was considered after excluding other conditions. Unfortunately, the child expired within 24 hours following extubation. LOCCHS should be contemplated in children with unexplained hypoventilation who are challenging to extubate, particularly in the absence of underlying neurological, pulmonary, or cardiac diseases.

The Diagnostic Assessment of Platelet Function Defects.

Congenital platelet disorders are rare and targeted treatment is usually not possible. Inherited platelet function disorders (iPFDs) can affect surface receptors and multiple platelet responses such as defects of platelet granules, signal transduction, and procoagulant activity. If iPFDs are also associated with a reduced platelet count (thrombocytopenia), it is not uncommon to be misdiagnosed as immune thrombocytopenia. Because the bleeding tendency of the different platelet disorders is variable, a correct diagnosis of the platelet defect based on phenotyping, function analysis, and genotyping is essential, especially in the perioperative setting. In the case of a platelet receptor deficiency, such as Bernard-Soulier syndrome or Glanzmann thrombasthenia, not only the bleeding tendency but also the risk of isoimmunization after platelet transfusions or pregnancy has to be considered. Platelet granule disorders are commonly associated with either intrinsically quantitative or qualitative granule defects due to impaired granulopoiesis, or granule release defects, which can also affect additional signaling pathways. Functional platelet defects require expertise in the clinical bleeding tendency in terms of the disorder when using antiplatelet agents or other medications that affect platelet function. Platelet defects associated with hematological-oncological diseases require comprehensive information about the patient including the clinical implication of the genetic testing. This review focuses on genetics, clinical presentation, and laboratory platelet function analysis of iPFDs with or without reduced platelet number. As platelet defects affecting the cytoskeleton usually show thrombocytopenia, but less impaired or normal platelet functional responses, they are not specifically addressed.

Congenital myasthenia syndrome due to CHRNA1 mutation resulting in respiratory failure

CMS is an inherited disorder, characterized by defective transmission at Neuromuscular Junction affecting from birth or soon after. It results in fatigue and muscle weakness because of genetic abnormalities that interfere with the neuromuscular junction's ability to function. The most typical signs of CMS include eyelid drooping, breathing difficulties, muscle weakness and weariness with variations depending on specific genetic mutations. Clinical examinations, neurophysiologic tests, and genetic analyses are frequently combined to make the diagnosis of CMS. Although there is no known treatment for CMS, many patients may control their symptoms and lead relatively normal lives with the right care. A newborn with CMS due to CHRNA1 gene mutation is described in this article, along with its very early onset. The CHRNA1 mutation is a rare variant in the Indian population. Due to muscle weakness, the neonate in this case developed severe respiratory distress and later succumbed to death despite rigorous life-saving measures.

Impact of Hepatoblastoma on Infectious Complications Following Pediatric Liver Transplantation.

Liver transplantation is the standard therapy for end-stage liver disease in pediatric patients with biliary atresia (BA), congenital and metabolic conditions, and for an unresectable malignant tumor like hepatoblastoma (HB). BA is the leading indication for pediatric liver transplantation, while HB is the most common childhood liver cancer. Despite improved outcomes through advanced surgical techniques and novel immunosuppression, pediatric liver transplantation (pLT) is complicated by post-transplant infections. A retrospective review was performed of pLT recipients at Cincinnati Children's Hospital Medical Center (CCHMC) and stratified patients by underlying disease to assess impact on post-transplant infectious events. BA patients were youngest at pLT (12.5 months; p < 0.001) compared to other disease cohorts (HB 30.8, other 43.7). All HB patients received organs from deceased donors. In the year following pLT, 93% of the patients experienced at least one infectious event (IE). HB patients had the highest mean number of IE across disease groups (5.5 IE/patient vs. BA 4.5, other 4.0; p = 0.055), with significantly more patients with fever and neutropenia (p < 0.001) and EBV infections (p = 0.012). HB patients were more likely to develop IE earlier after pLT than non-HB groups (p = 0.013), especially Clostridioides difficile (p < 0.01) and fever and neutropenia (p < 0.01). Despite having variable IE experiences, 1-and-5-year survival across disease groups were similar. IE were frequently observed in HB patients after pLT, possibly related to pre-and-postoperative chemotherapy and associated neutropenia. Underlying disease may help inform targeted infection-related patient management following pLT.

Spectrum of Otological Manifestations in Treacher Collins Syndrome: A Case Series of 9 Patients.

Treacher Collins syndrome (TCS) is an uncommon congenital disorder predominantly involving craniofacial, orbital, and otological structures. The various ear malformations seen in 9 patients with TCS are described. TCS predominantly affects the external and middle ear structures, with inner ear structures being relatively spared, not unexpected given the dual embryological origin of the human ear. The external and middle ear malformations were categorized and graded as those involving the ear pinna, external auditory canal, tympanic cavity, ossicles, facial nerve canal, oval window, and bony labyrinth for all 9 patients. The ear malformations were symmetric in the majority, and the patients with higher grades of microtia were found to have a more severe category of other otological malformations.

Growth and Survival of a Cohort of Congenital Zika Virus Syndrome Children Born With Microcephaly and Children Who Developed With Microcephaly After Birth.

Little is known about the clinical course of children born with congenital Zika virus syndrome (CZS). This article aimed to analyze the growth and survival of children with CZS born with microcephaly and children who developed with microcephaly after birth in the 36-month period. This is a cohort of children diagnosed with CZS who were monitored in a series of outpatient appointments, with clinical and demographic information and anthropometric measurements collected. The Mann-Kendall test evaluated the trend of the mean Z-score of head circumference (HC) for age and the Kaplan-Meier model described the time to low weight and short length according to the classification of HC at birth. Children born without microcephaly had a reduction in HC growth velocity (P = 0.019) and took longer to reach low weight (P = 0.036) and short length (P = 0.034) when compared with those born with microcephaly. Seven (10%) deaths were reported, and the probability of survival after 36 months of age was 88%. In children with arthrogryposis, the risk of death was 7 times as high as in those without this condition (adjusted hazard ratio: 6.49; 95% confidence interval: 1.31-32.20; P = 0.022). In this cohort of children with CZS, 20% were born without microcephaly and all of them presented a reduction in HC growth velocity, which led to microcephaly. Progression to low weight and short length occurred in the first years of life, and that was faster in those born with microcephaly. Healthcare providers should be aware of these conditions that pose a risk of unfavorable anthropometric measurements and death.

Pregnancy With Congenital Abnormalities from Marriage of a Different Ethnic: a Very Rare Case

Bladder exstrophy (BE) is one of the rare congenital abnormalities. This congenital disorder is also serious, with characteristics such as a spectrum of disorders involving the walls of the ventral body, the urogenital tract, the pelvis, the spine, and the anus. The incidence rate of this case is 1 per 30,000 to 50,000 live births. The case study reported the findings of congenital bladder extrophy in a 29-year-old Acehnese woman married to an Indian citizen, with a diagnosis of G3P0A2 38-39 weeks pregnant, coming with complaints. The mother felt the discharge of water. The patient admitted to being 9 months pregnant with HPHT 27/1/2021 and TTP 3/11/21 according to the gestational age of 38-39 weeks. The patient has a history of the disease with type 2 diabetes mellitus. Initial laboratory examination findings showed hyperglycemia at 256 mg/dL. Ultrasound examination found a single head presentation of the fetus alive with a mass in the abdomen of the fetus. The patient is planning to have an emergency cesarean section and is consulted by the internal medicine department for blood sugar regulation. Postpartum findings in infants with hernia, umbilical cord, Bladder Exstrophy, epispadia, and symphysiolysis will be consulted to the Division of Pediatric Surgery. This case report describes a pregnancy with congenital abnormalities and Bladder Exstrophy. Prenatal diagnosis allows the medical team to prepare for a multispecialty approach. It also gives parents time to prepare and adjust to expectations related to labor and the neonatal period, as well as potential complications and long-term prognosis.

Post-Marketing Safety of Temozolomide: A Pharmacovigilance Study Based on the Food and Drug Administration Adverse Event Reporting System.

Temozolomide (TMZ) is a widely used chemotherapy agent for the treatment of malignant gliomas and other brain tumors. Despite its established therapeutic benefits, there is an ongoing need to understand better its safety profile, particularly in real-world clinical settings. This study aimed to identify critical adverse drug reactions (ADRs) associated with TMZ by utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby providing valuable safety insights for clinical practice. We utilized the reported odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayes Geometric Mean as primary algorithms for disproportionality analysis. Adverse events (AEs) were classified as ADRs only upon meeting the criteria set by all four algorithms. To ensure the accuracy of our results, we meticulously excluded any AEs deemed unrelated to TMZ. From October 2003 to September 2023, a total of 10,502,538 case reports and 9,073 cases explicitly attributed to TMZ were retrieved from the FAERS database. After applying our filters, 116 ADRs, each with a corresponding Preferred Term (PT), were identified across 18 System Organ Classes (SOCs). The identified ADRs associated with TMZ primarily involved bone marrow suppression, hepatotoxicity, and various infections, notably Pneumocystis jirovecii pneumonia. Furthermore, our analysis identified valuable ADRs not listed in the drug label, including congenital, familial, and genetic disorders at the SOC level, as well as unexpected ADRs at the PT level, such as seizures, pulmonary embolism, and sepsis. This real-world pharmacovigilance study has identified significant and previously unreported ADRs associated with TMZ. Further research for validation and resolution is urgently needed to guide the clinical application of TMZ, ensuring the safety and efficacy of its use in treating brain tumors.

Transcatheter Aortic Valve Implantation (TAVI) in Bicuspid Anatomy

Bicuspid aortic valve (BAV) stenosis, a common congenital condition, presents unique challenges for transcatheter aortic valve replacement (TAVI) due to anatomical variations like cusp morphology, coexisting aortopathy and calcification. TAVI offers a viable option for BAV patients with refinements in technique and technology, though ongoing research is essential to optimize patient-specific approaches and long-term results. Key considerations for TAVI in BAV include precise valve sizing, positioning, and the need for rigorous pre-procedural imaging to mitigate risks such as paravalvular leak and stroke. Early results show TAVI’s safety and efficacy are comparable to surgery, though BAV patients undergoing TAVI often are exposed to higher rates of post-procedural pacemaker implantation. Emerging data on next-generation self-expandable (SE) and balloon-expandable (BE) valves reveal that while both offer success in this complex anatomical aortic valve variation, gaps remain in the long-term durability and management of BAV-related aortopathy. This review examines the latest advancements in TAVI for BAV, emphasizing how specialized approaches and device selection address BAV’s complexities.

Understanding Host–Pathogen Interactions in Congenital Chagas Disease Through Transcriptomic Approaches

Chagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route of infection, involving intricate maternal–fetal immune interactions that challenge diagnosis and treatment. This review synthesizes findings from three RNA-seq studies that explore the molecular underpinnings of congenital Chagas disease, emphasizing differentially expressed genes (DEGs) implicated in host–pathogen interactions. The DAVID tool analysis highlighted the overexpression of genes associated with the innate immune response, including pro-inflammatory cytokines that drive chemotaxis and neutrophil activation. Additionally, calcium-dependent pathways critical for parasite invasion were modulated. T. cruzi exploits the maternal–fetal immune axis to establish a tolerogenic environment conducive to congenital transmission. Alterations in placental angiogenesis, cellular regeneration, and metabolic processes further demonstrate the parasite’s ability to manipulate host responses for its survival and persistence. These findings underscore the complex interplay between the host and pathogen that facilitates disease progression. Future research integrating transcriptomic, proteomic, and metabolomic approaches is essential to unravel the molecular mechanisms underlying congenital Chagas disease, with a particular focus on the contributions of genetic diversity and non-coding RNAs in immune evasion and disease pathogenesis.

Diagnostic and therapeutic approach to unilateral posterior vertical insufficiency

The aim of this article is to present the diagnostic and therapeutic approach to unilateral posterior vertical insufficiency. The authors describe the management protocol. Posterior vertical insufficiency (PVI) manifests clinically as obliquity of the maxillo-mandibular occlusal plane and bicommissural line, and deviation of the chin. Radiographically, PVI is characterized by an elevation of the mandibular angle in relation to the base of the odontoid. Among the etiologies, congenital disorders are the most frequent, dominated by condyle hypoplasia. First and second branchial arches syndromes are most often associated to soft-tissue malformations, while acquired etiologies (post-traumatic, ankylosis and rheumatic) are scarce. Therapeutic management requires close collaboration between orthodontist and surgeon and involves alternative orthognathic surgical procedures. Three techniques are described along with their expected results: chondro-costal grafting, vertical retro-spinal lengthening using the Caldwell-Letterman technique, and intra-oral supra-basilar osteotomy. Although the clinical presentation can be frustrating in children, facial asymmetry usually increases during pubertal growth. Early treatment with dentofacial orthopedics can sometimes restore growth. In other cases, collaboration between orthodontist and surgeon is more necessary than ever to correct asymmetry, sometimes using unconventional surgical technique.

Fragment-Based Drug Discovery of KIF11 Inhibitors for Glioblastoma Treatment: Molecular Insights and Therapeutic Potential.

Fragment based novel drug identification and its validation through use of molecular dynamics and simulations.Comparing primary microcephaly genes with glioblastoma expression profiles reveals potential oncogenes, with proteins that support growth and survival in neural stem/progenitor cells likely retaining critical roles in glioblastoma. Identifying such proteins in familial and congenital microcephalic disorders offers promising targets for brain tumor therapy. Among these, KIF11, a kinesin motor protein (KSP), stands out as a significant oncogene. Expression analyses across various cancer types, including glioblastoma, demonstrate its overexpression in brain tumor patients. Using a targeted fragment-based drug discovery approach, we explored alternative small molecule inhibitors for KIF11. Existing drugs, such as ispinesib, are limited by side effects and multidrug resistance. Through molecular docking and simulations, we identified three candidate drug fragments. Further analysis confirmed that Mol-121026 exhibits a more stable interaction with KIF11 compared to ispinesib. Detailed analyses indicate that Mol-121026 binds to the same active site as the reference drug, effectively inhibiting KIF11's mechano-chemical activity. Importantly, Mol-121026, a derivative of 3-phenyl-1H-pyrazol-5-carboxylic acid, offers a promising alternative due to its lower molecular complexity, ability to target allosteric sites, and potential for optimization into a potent and effective drug candidate. Our findings identified Mol-121026 as a top candidate with a docking score of -10.2 kcal/mol and MM/GBSA binding energy of -19.10 kcal/mol. Molecular dynamics simulations revealed stable interactions with key residues GLU116 and GLU118, supporting its potential as a promising KIF11 inhibitor.

P0984 Treatment with allopurinol and low-dose azathioprine during pregnancy in patients with Inflammatory Bowel Disease. A Danish single center experience

Abstract Background Low-dose azathioprine in combination with allopurinol (LD-AZA/ALLO) is a widely used treatment option in inflammatory bowel disease (IBD). Data on pregnancy and birth outcomes from exposure to combination therapy are sparse. The aim of this study was to provide data on safety and risk for adverse pregnancy and birth outcomes in women with IBD treated with LD-AZA/ALLO at the Gastrounit, Hvidovre Hospital, Copenhagen. Methods The study was a retrospective single center study. Inclusion criteria were established IBD diagnosis and treatment with LD-AZA/ALLO (AZA 50-75 mg/ ALLO 100 mg) during conception and pregnancy between 2013-2023. Data was collected from electronic medical charts and by questionnaire to all included women. Data registered was; demographics, diagnosis, disease characteristics, disease activity, IBD medications and number of pregnancies. Pregnancy outcomes were neonatal characteristics, obstetric complications, lactation and congenital malformations, disease, infections and admission to the hospital during the first year of life. Results In all, 44 women with 62 pregnancies (one twin pregnancy) and 59 live births were included. There were 1 spontaneous and 3 provoked abortions due to genetic disorders (1 trisomy 21 and 2 spinocerebellar ataxia). Obstetric complications were present in 8 (13%) pregnancies, (1 pre-eclampsia, 1 HELLP syndrome, 6 hypertension and/or gestational diabetes mellitus). 7 (11%) women had an IBD flare during pregnancy, none resulting in obstetrical complications. 5 (9 %) children were born prematurely, 4 (7 %) had low birth weight. No congenital malformations were reported. One child was born with facial nerve paralysis and later diagnosed with hyper-IgD syndrome. 8 (14 %) were admitted to neonatal ward (hours to days), mainly due to immature lungs. During the first year of life, one child was admitted to the hospital due to COVID. One child was suspected to have an immune defect, but all symptoms and biochemical abnormalities resolved and interpreted as side effect to LD-AZA/ALLO. 5 children (9%) were treated with antibiotics due to minor infections. In total 84 % of the children were breastfed during LD-AZA/ALLO treatment. Conclusion In this large single center experience with 62 pregnancies in women treated with LD- AZA/ALLO, no malformations or indications of increased risk of complications of pregnancy and birth were observed. The majority of children were breastfed and no serious signals or complications were reported first year of life. Treatment with LD-AZA/ALLO during pregnancy and breastfeeding seems safe.

Evolution of long scalp hair in humans.

The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago. Long scalp hair in AMHs was also a trait that was selected because it conveyed essential signals related to an individual's age, sexual maturity, health and social status. Biologically, hair length is primarily determined by the amount of time that a hair follicle spends in the active growth phase (anagen). While anagen duration is typically tightly regulated in most mammals, the inherent ability of a hair follicle to continuously recruit new dividing progenitors to its base, where hair fibre is generated, theoretically removes limits on maximal anagen duration. We propose a model wherein hair cycle progression into and out of anagen is regulated by evolutionary malleable molecular checkpoints. Several animal species and domesticated animal breeds display long body hair, which suggests that extremely long scalp hair in humans emerged via attenuation of an existing out-of-anagen checkpoint mechanism rather than via a newly evolved molecular programme. Studying congenital and somatic mosaicism conditions featuring altered hair length could potentially unveil the currently unknown molecular basis underlying this human trait.

Identification of novel RIPK4 variants in a Chinese patient with Arthrogryposis Multiplex Congenita (AMC)

BackgroundArthrogryposis multiplex congenita (AMC) is a congenital disorder characterized by multiple joint involvement, primarily affecting limb mobility and leading to various tissue contractures. Variations in the RIPK4 gene may impact connective tissues, thereby resulting in a spectrum of malformations. This study aimed to identify the genetic etiologies of AMC patients and provide genetic testing information for further diagnosis and treatment of AMC.MethodsWe recruited a Chinese female patient with hand-related AMC and her family members. Whole-exome sequencing (WES) was employed to determine the genetic etiologies of the patient’s disease. The pathogenic mechanisms of the identified variations were analyzed using protein tolerance profiling and modeling.ResultsWe identified two novel RIPK4 variants (c.1354G > A, p.E452K; c.1558A > T, p.T520S). Pathogenicity studies indicated that the c.1354G > A, p.E452K variant changed the charge from negative to positive and altered the chemical properties from acidic to alkaline, potentially significantly affecting protein function.ConclusionsWe reported the discovery of two novel RIPK4 variants (c.1354G > A, p.E452K; c.1558A > T, p.T520S) in a Chinese AMC female patient’s family. Our study enhances the genetic repository for AMC and highlights the pathogenicity of RIPK4 variants, underscoring the significance of comprehensive management for genetic-related diseases, particularly the critical roles of prenatal diagnosis and genetic counseling.Trial registrationThe research protocol received approval from the Ethics Review Committee of Xiangya Hospital of Central South University in China (approval number: 202103427), registered in March 2021, with all participants providing duly signed informed consent forms.

Clinical and genetic diagnosis of first cohort of differences of sexual development in the Iranian population.

Differences of sex development (DSD) refer to various congenital conditions affecting the urogenital and hormonal systems. Accurate diagnosis and personalized management are crucial for supporting patients through complex decisions, such as those related to gender identity. This study represents the first comprehensive investigation into DSD inIran, analyzing patient's clinical and genetic data between 1991 and 2020. Karyotype analysis was performed on 69 patients without a molecular diagnosis, with sex chromosome DSD excluded. Presence of SRY gene evaluated in all sex reversal patients. Whole exome sequencing (WES) was used for 26 undiagnosed patients, revealing pathogenic variants in WT1, NR5A1, DHX37, AR, CYP17A1, and LHCGR genes. The most common diagnosis was testicular TDSD, identified in 42 patients (60.86 %), with the SRY gene being the primary cause in 36 of these patients. The study highlights the importance of genetic analysis in identifying novel and rare gene variants, particularly within the steroid hormone and gonad differentiation pathways, for both 46, XY and 46, XX DSD. These findings emphasize the need for genetic analysis in providing personalized patient care and tailored counseling to help individuals navigate complex decisions, including those involving gender identity.

A rare case of unilateral facial infiltrating lipomatosis: summary of medical and dental implications

Introduction Facial infiltrating lipomatosis (FIL) is a rare congenital and benign condition, resulting from mature nonencapsulated adipocytes penetrating into neighbouring structures. Individuals with FIL present with unilateral facial and craniofacial hemihypertrophy, alongside various medical and dental complications of the affected side. Case report At birth, the infant had an evident right sided facial swelling which remained asymptomatic but continued to increase in size. Magnetic resonance imaging confirmed right-sided lipomatous hyperplasia and genetic testing confirmed a somatic mutation to PIK3CA; the cause of cell hyperproliferation, often identified in FIL cases. On the right side, the child has developed epidermal naevus and mild hearing and visual impairment. A multidisciplinary team (paediatric medicine and dentistry, dermatology, ENT and plastics at Great Ormond Street Hospital) has contributed to managing the complex condition. At 12 months old, paediatric dentistry observed premature eruption of teeth 53, 54 and 84 and hyperplasia of the upper right alveolar arch. At 5 years-old, the child presented with premature exfoliation of primary teeth and premature eruption of permanent teeth 14, 16, 41, 42 and 46 with bilateral crossbites. Management A dental prevention regime has been implemented and the child remains caries free. The developing dentition will continue to be monitored with consideration of orthodontic management. Presently, as the child remains stable, a conservative approach without surgical or medical intervention has been adopted. His vision is corrected with glasses. Conclusion FIL is associated with dental developmental anomalies and medical complications of the affected side, requiring multidisciplinary care.