Genetic Conditions Research Articles

Phytochemical Interventions for Polycystic Ovary Syndrome : (PCOS) Systematic Review

Worldwide, 2.2-26% Many women who are fertile experience PCOS, a complicated the Endocrine, metabolic, and genetic condition. Pale menstruation, infertility, hirsutism, acne, and insulin resistance are some of the symptoms of PCOS, which is typified by polycystic ovaries, persistent anovulation, and hyperandrogenism. While they come with risks and adverse effects, conventional treatments frequently target specific ailments. Herbal remedies, on the other hand, present a viable, low-risk substitute. The effectiveness of several botanicals, such as Ashoka, Shatavari, Lodhra, Guduchi and Haritki in reducing PCOS symptoms is highlighted in this review. These herbs improve ovarian morphology and lower hyperandrogenism; they also have hypoglycemic, anti-obesity, and hormone-regulating qualities. Other herbs that are useful for hormone imbalance, reproductive dysfunction, depression, menstruation include The plants Phyllanthus emblica and Bauhinia variegata. Bellirica terminalia. Hypericum perforatum with Tribulus terrestris. anomalies. Notably, there have been no documented adverse effects and these phytotherapeutic approaches are well tolerated. The goal of this review is to compile the body of research regarding the use of natural plants to treat PCOS, with a focus on the possibility of herbal formulations as a safe, effective, supplemental management strategy for condition.

Abstract A008: Identification of EYA2 as a promising biomarker for DICER1-related tumor predisposition

Abstract Background: DICER1-related tumor predisposition (DRTP), also known as DICER1 syndrome, is a genetic condition associated with an increased risk of developing various tumors, including pleuropulmonary blastoma, thyroid gland neoplasia, ovarian tumors, and cystic nephroma. Currently, the diagnosis and surveillance of DRTP primarily relies on genetic testing for DICER1 mutations. There is a pressing need for surrogate diagnostic biomarkers to improve early detection and monitoring. Objective: To identify and validate EYA2 as a potential biomarker for DICER1-related tumor predisposition. Methods: Murine mesenchymal stromal cell lines were developed to model the consequences of DICER1 mutations, including the DICER1E1705K mutation found in DRTP. Both bulk RNA sequencing (RNAseq) and microRNA sequencing (miRNAseq) were employed to identify differentially expressed mRNAs in these cell lines. The RNA and protein levels of Eya2 were measured by qRT-PCR and Western blot, respectively. De-repression of Eya2 mRNA by miRNA was evaluated by dual luciferase assay to link overexpression with the DICER1 defect of DRTP. Then, immunohistochemistry staining of EYA2 was performed on a panel of DRTP tumors. Results: We found that more than 2000 mRNAs were derepressed in mesenchymal stromal cells expressing DICER1E1705K as compared to DICER1WT. Among these, Eya2 emerged as a top candidate. We observed elevated Eya2 mRNA and protein levels in DICER1E1705K -expressing mesenchymal stromal cells. Utilizing a reporter assay, we also observed de-repression of the 3’ UTR of Eya2 upon expression of DICER1E1705K as compared to DICER1WT. Strong nuclear EYA2 staining was observed in a subset of DRTP tumor samples. Conclusion: Elevated EYA2 expression in tumor tissues from DRTP patients supports its potential use in both diagnostic and surveillance contexts. Further studies are warranted to validate EYA2 as a clinical biomarker and explore its utility in improving early detection and monitoring strategies for individuals at risk of DRTP. Citation Format: Mona Wu, Shengmei Zhou, Felix Kommoss, Yemin Wang, James F Amatruda. Identification of EYA2 as a promising biomarker for DICER1-related tumor predisposition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A008.

DEALING WITH TWO SYNCHRONOUS LESIONS

Introduction Multiple synchronous intracranial lesions present a significant diagnostic and therapeutic challenge, in most cases appearing as metastatic tumors or same-cell type tumors. Case Report We report the case of a 73-year-old patient admitted in our department with light left hemiparesis (MRC MMT 4/5), light left hypoesthesia and transitory and remitted state of temporo-spatial confusion that debuted around six weeks prior to presentation. The neurological exam confirmed the sensorimotor deficit and displayed the existence of left neglect syndrome. The patient’s MRI revealed a giant temporo-parieto-occipital mass almost 7 cm in diameter that appeared to have an intraventricular starting point and showed a relatively homogeneous contrast enhancement with significant mass effect. A concomitant superficial parieto-temporal lesion was also noted. Both lesions were excised in a successive manner from superficial to deep, using a right parieto-temporal craniotomy. While the giant mass had a yellowish color and an extremely hard consistency, the superficial one was easily suctionable and had a grey-reddish color and was extremely well vascularized, raising the suspicion of concomitant brain lesions of different histology. Postoperatively the patient underwent a routine thoracic CT scan in the context of a position related soft tissue injury that revealed the existence of two pulmonary lesions, further deepening our suspicion of concomitant brain lesions of different histology. Conclusions Although extremely rare, the appearance of two histologically distinct brain lesions in patients with no evidence of a genetic condition should be taken into consideration especially in the context of intraoperative differences in order to successfully guide the patients’ follow-up treatment.

E' il momento di un buon Caffey

It is a rare genetic condition characterized by bone proliferation and cortical thickening due to a genetic mutation.The infantile form appears in the first months of life, with subperiosteal bone deposits, and generally resolves by the age of two without sequelae.

Inflammatory Bowel Disease in Activated PI3Kδ Syndrome: An Uncommon Complication of a Rare Condition

Background/Objectives: Monogenic primary immunodeficiencies represent a group of disorders with varying levels of severity, many of which remain poorly understood. Activated phosphoinositide-3 kinase delta syndrome (APDS) is a rare genetic condition resulting from dominant point mutations in the phosphoinositide-3 kinase delta (PI3Kδ) gene, which leads to hyperactivation of the PI3Kδ enzyme, primarily expressed in T and B lymphocytes. Children with this mutation often have recurrent sinopulmonary infections and immunodeficiency. Additional complications may include increased susceptibility to herpes virus infections, lymphoid hyperplasia, and autoimmune conditions. In this case, report, we describe the clinical course of a young boy diagnosed with APDS who developed unclassified inflammatory bowel disease (U-IBD) and explore a personalized treatment approach. Methods: We detail the clinical course of a 12-year-old boy with APDS who presented with fever, diarrhea, anemia, and significant weight loss. Diagnostic evaluations, including endoscopy and histological analysis, led to a diagnosis of U-IBD. Genetic testing confirmed a heterozygous PIK3CD mutation (c.G3061A, p.E1021K). Results: Although APDS is characterized by a broad spectrum of immune dysregulation, the occurrence of IBD in this context is rare. We managed the patient’s IBD with exclusively enteral nutrition to induce remission, followed by a maintenance regimen combining the Crohn’s Disease Exclusion Diet (CDED) and mesalamine, achieving sustained long-term clinical remission. Conclusions: This case underscores the importance of personalized treatment approaches in managing the complex manifestations of APDS.

Quando l'anemia blocca le gambe

A 17-month-old girl was hospitalized for dehydration due to gastroenteritis. She presented with a severe microcytic anaemia (Hb 6.2 g/dl) linked to an exclusive breastfeeding diet. Attempts at introducing solid foods had failed. Despite improvement in anaemia and diet after discharge, she showed motor regression and ceased to walk. Neurological tests excluded traumatic, metabolic and genetic conditions, but anaemia persisted. Following a blood transfusion, the patient regained motor abilities. The paper highlights the link between iron deficiency and developmental delays, particularly in walking. This case underscores the vital role of iron in neurodevelopment and emphasises awareness of chronic anaemia in children worldwide.

EPCO-59. FIRST CASE REPORT OF COMBINED GERMLINE NF1 AND BRCA2 MUTATIONS PRESENTED WITH NEUROFIBROMAS AND LIPOMATOSIS

Abstract Both Neurofibromatosis type 1(NF1) and BRCA2 are common tumor suppressor genes, with mutations in each associated with genetic tumor syndromes. However, it is extremely rare to observe two different germline mutations in one patient. To the author’s knowledge, this is the first case report of a patient with germline mutations in both pathological NF1 and BRCA2 genes. We report a 41-year-old male patient with neurofibromas and lipomatosis. The patient with known family history of NF1, was diagnosed with NF1 after skin biopsy at 28 years old. At 40 years old, he underwent resection of a large intrathoracic neurofibroma. For genetic confirmation, next generation sequencing test was performed on both the intrathoracic neurofibroma tumor sample and saliva sample, revealing unexpected pathological germline mutation in both NF1 and BRCA2 genes. Consequently, the patient underwent resection of multiple lesions in the chest, abdomen, and upper extremities due to concern for potential breast cancers, and pathology of these lesions predominantly showed lipomas and one angiolipoma. Patient has family members with NF1 including a maternal aunt, a maternal cousin, and one son. However, there is no family history of lipomatosis or cancers commonly associated with BRCA2 mutation such as breast, ovarian, pancreatic, or prostate cancer. While lipomas are reported in patients with NF1, it is unusual that patient does not have typical café-au-lait spots or multiple neurofibromas but instead has multiple lipomas. This unusual presentation may be related to his unique genetic condition involving germline mutations in two tumor suppressor genes. Long term follow-up with screening tests for known tumors associated with each genetic mutation will be essential.

QOL-30. DIETARY CONSIDERATIONS FOR PEOPLE WITH NF1: A SYSTEMATIC REVIEW OF THE LITERATURE

Abstract BACKGROUND Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic condition. Limited pre-clinical and clinical data suggests that certain metabolic disturbances, body composition differences and nutritional deficiencies may be more prevalent in people with NF1. Data on the role of dietary patterns in people with NF1 and their effects in NF1-related manifestations is scarce. METHODS A systematic literature review was conducted; the MeSH database of PubMed was utilized to identify controlled vocabulary and key words associated with NF1, diet, and nutrition. These terms were combined using boolean operators to query PubMed, Embase, PLOS One, and Cochrane. The inclusion criteria consisted of articles in English, full text available, human studies, published between 2000-2024. The results were screened and key details were extracted. RESULTS 394 published articles were identified, out of which 15 met the inclusion criteria. 379 papers were excluded due to duplication or not meeting all inclusion criteria. Manuscripts included case reports, case series, retrospective and prospective studies, including a phase 2a clinical trial that only included six participants. Topics included vitamin D and bone metabolism, nutritional supplements, glucose metabolism, and nutritional intake. CONCLUSIONS Data regarding the effects of diet or nutritional supplements in people with NF1 is limited. Available studies suggest that a diet composed of therapeutic elements, including but not limited to, medium-chain fatty acids, calcium, and vitamin D, aids in bone growth and density, and muscle lipolysis. A single clinical trial suggests that L-carnitine supplementation is safe and feasible and might result in improved functional muscle performance in children with NF1. These conclusions might only be applicable to a small population of people with NF1 and did not result in conclusive significant clinical benefit. Further research is needed to better comprehend the role that nutrition plays in patients’ quality of life.

TMOD-10. ESTABLISHMENT OF ADULT AND PEDIATRIC BRAZILIAN PRE-CLINICAL MODELS FOR HIGH-GRADE GLIOMAS

Abstract High-grade gliomas (HGG) are the most aggressive brain tumors, necessitating robust and representative preclinical models for therapeutic research. We established primary cultures and patient-derived xenograft models from three pediatric high-grade gliomas (pHGG) and one adult IDH wild-type glioblastoma (GBM IDHwt) Brazilian patients. The first pHGG case, from an 11-year-old with PDGFRA (c.1977C>G) and TP53 (c.637C>T) mutations, led to the development of the HCB570 primary culture, PDX and patient-derived orthotopic xenograft (PDOX) OXP9. The second pHGG, from an 11-year-old with CMMRD syndrome and MSH6 germline mutation, resulted in the HCB589 primary culture, PDX and PDOX OXP22. The third pHGG case, from a 14-year-old with diffuse midline glioma harboring an H3F3A mutation, established the HCB604 primary culture and PDX OXP32. The HCB612 primary culture and PDX GBM1, were established from an adult patient with GBM IDHwt, TERT mutated, with no MGMT promoter methylated. The primary cultures showed varied proliferative rates, with an average doubling time of 55 hours. All cultures demonstrated colony-formating capability, with an average IC50 of 750µM for temozolomide (TMZ) exposure. Immunohistochemical and EPIC methylation profiles confirmed that the PDX models closely resemble the patient features. Our establishment of diverse preclinical models, including those derived from patients with rare genetic conditions such as CMMRD, provides valuable insights into HGG pathogenesis and potential therapeutic strategies. The present Brazilian patient-derived models enrich glioma research inclusion diversity and foster future personalized treatment approaches.

Hereditary haemochromatosis: A review.

Hereditary haemochromatosis (HH) is the commonest genetic condition among populations of Northern European ancestry. Mutations to the HFE gene leads to uninhibited intestinal iron absorption followed by excess iron deposition in various organs such as the liver, pituitary gland, pancreas and heart. Due to variable biochemical and clinical penetrance, not all individuals with C282Y homozygosity will develop HH. Early diagnosis is crucial to prevent morbidity and mortality but is challenging with most patients not exhibiting any symptoms. Patients with HH should undergo clinical assessment to evaluate their symptoms, presence of organ damage and hepatic fibrosis using transient elastography. Patients who are negative for the HFE mutations but have significant liver iron loading seen on magnetic resonance imaging should be reviewed by a specialist and considered for genetic tests looking for the rarer non-HFE mutations. HH patients are predominantly treated with venesection which can improve symptoms, hepatic fibrosis and mortality.

Management of Prenatal Expanded Genetic Carrier Screening Results for Autosomal Recessive Sensorineural Hearing Loss.

Expanded carrier screening (ECS) identified couples at-risk to have a baby with an autosomal recessive genetic condition. Several genes implicated in sensorineural hearing loss (SNHL) are included in prenatal or preconception genetics ECS testing. Early identification of SNHL risk may enable prognostication of hearing loss, early educational intervention, and minimization of unnecessary diagnostic testing. We sought to describe cases where ECS enabled early SNHL-risk identification. Retrospective chart review. Maternal-Fetal Care Center and Otolaryngology department at an academic tertiary hospital. Medical records of parent-infant dyads with positive ECS results for variants in autosomal recessive SNHL genes were reviewed. Data regarding genetic diagnostic testing, newborn hearing screening, time to HL diagnosis, audiological evaluation, and clinical consultations were compiled. Fifteen pregnant with positive ECS results for SNHL were referred for consultation with a pediatric otolaryngologist and genetic counselor. Generally, these couples were highly educated and adequately insured. 14 had pathogenic variants for GJB2 and 1 for USH2A. Four couples pursued prenatal genetic diagnosis via amniocentesis; 11 couples deferred genetic testing to the postnatal period or waited for initial hearing evaluation. Six babies inherited biallelic GJB2 mutations. Four were found to have SNHL on ABR by age 5 weeks and received follow-up management, 1 had a normal hearing evaluation despite being gene-positive, and 1 was lost to follow-up before hearing evaluation. Carrier screening and confirmatory prenatal or neonatal genetic testing provided considerable lead time for early audiometric testing and appropriate intervention services including hearing aid fitting.

Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand

Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline using Oxford Nanopore Technologies PromethION 2 solo system and Fabric GEM™ software. Benchmarking of the pipeline was performed using Global Alliance for Genomics and Health benchmarking tools and Genome in a Bottle samples (HG002-HG007). Evaluation of single nucleotide variants resulted in a precision and recall of 0.997 and 0.992, respectively. Small indel identification approached a precision of 0.922 and recall of 0.838. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 were reliably detected with ~2 M long reads. Finally, we present results obtained from fourteen trio samples, ten of which were processed in parallel with a clinically accredited short-read rapid genomic testing pipeline (Newborn Genomics Programme; NCT06081075; 2023-10-12).

Goals of Surgical Interventions in Youths Receiving Palliative Care

Most youths receiving palliative care undergo many surgical interventions over their lifetimes. The intended purposes of interventions in the context of goals of care are not commonly articulated. To describe the goals and purposes of surgical intervention in youths receiving palliative care and propose a framework discussing intervention using goal-oriented language. This retrospective cohort analysis was conducted among a subset of patients enrolled between April 2017 and March 2021 in a prospective multicenter cohort study of youths receiving palliative care (the Pediatric Palliative Care Research Network's Shared Data and Research [SHARE] Study). Patients younger than 30 years receiving palliative care services were eligible for inclusion in SHARE, and all enrolled at Boston Children's Hospital/Dana Farber Cancer Institute, a SHARE site, were included in this study. Goals and purposes of all surgical interventions from the time of diagnosis through the present were abstracted from patient records. A goal and purpose framework was generated using a hybrid deductive-inductive approach based on established goals-of-care frameworks and the clinical context of surgical interventions. Data were analyzed in September 2023. Primary outcomes included goals and purposes of surgical interventions performed in the study population. Among 197 youths receiving palliative care (mean [SD] age at palliative care start, 8.01 [7.53] years; 108 male [54.8%]; 6 Asian [3.0%], 12 Black [6.1%], 129 White [65.5%], and 16 with >1 race [8.1%]; 27 Hispanic [13.7%] and 142 not Hispanic [72.1%]), almost all individuals (189 youths [95.9%]) underwent at least 1 surgical intervention (mean [SD] 17.5 [16.3] interventions; median [IQR] 13 [5-22] interventions). Of 3331 surgical interventions, there were 878 interventions (26.5%) conducted with the goal of life extension, 1229 interventions (37.1%) conducted for life enhancement, and 79 interventions (2.4%) conducted for both goals; the remaining 1130 interventions (34.1%) held neither goal. Most interventions were performed with the purpose of diagnosis (1092 interventions [32.9%]) or cure and repair (1055 interventions [31.8%]), with fewer performed for the purpose of placing or maintaining assistive technology (696 interventions [21.0%]) or for supportive (434 interventions [13.1%]) or temporizing (39 interventions [1.2%]) purposes. Patients with cardiovascular disease and cancers constituted approximately half (592 patients [56.1%]) of those undergoing curative or repair interventions, whereas youths with neurologic or genetic conditions constituted approximately half (244 patients [56.2%]) of those undergoing supportive interventions. In this cohort study, nearly all youths underwent surgical intervention, and the purposes of intervention differed by serious illness type. These findings suggest that conversations centered on a proposed framework concerning goals and purposes of surgical intervention may facilitate goal-concordant, high-quality care for youths with serious illness.

Multidimensional and Longitudinal Impact of a Genetic Diagnosis for Critically Ill Infants.

Many genetic conditions present in the NICU, where a diagnostic evaluation is pursued. However, understanding of the impact of a genetic diagnosis on clinical outcomes and health-related quality of life for these infants remains incomplete. We therefore evaluated parent-reported outcomes complemented by clinical outcomes measures over one year for a cohort of infants in the NICU undergoing genetic evaluation. Prospective cohort study evaluating outcomes after genetics consultation in a level IV NICU via parent report and electronic medical record review. Eligible infants were genetically undiagnosed at enrollment. Parent surveys were administered at baseline and 3, 6, and 12 months following enrollment and assessed genetic testing utility as well as parent-reported infant health-related quality of life using the Infant Toddler Quality of Life Questionnaire. A total of 110 infant-parent pairs were enrolled. Infants had a median age at enrollment of 15 days (interquartile range 8-37.75). At baseline, 74% (81/110) of parents endorsed high importance of finding a genetic diagnosis, but perceived importance significantly decreased over time. Over the study period, 38 infants received a molecular diagnosis per parent report, although this was discordant with electronic medical record review. Identification of a diagnosis did not significantly impact health-related quality of life across most domains, which was lower overall than population norms. A genetic diagnosis is highly desired by parents in the NICU, though waning interest over time for undiagnosed families may reflect parental emotional adaptation and acceptance. Additional supports are needed to improve perceived quality of life.

Cardiac involvement in dermatological disorders: A narrative review

Recent studies have highlighted several pathogenic connections between skin disorders and cardiac manifestations. Dermatologists frequently encounter several genetic or inherited skin conditions that can have significant cardiac implications, including septal defects, cardiomyopathy, and valvular heart disease, which may sometimes be life-threatening. In this review, primary cutaneous disorders having cardiac manifestations are described. A comprehensive narrative review of the literature was conducted by searching articles published through November 2023 in the PubMed and Google Scholar databases. Original research articles, review articles, case reports, case series and other relevant English-language publications were included. The review identified several congenital diseases, inflammatory conditions, connective tissue disorders, and adverse drug reactions that have both skin and cardiac involvement. Diagnosing these cardiac manifestations in patients with skin conditions is crucial for appropriate management, timely intervention and effective patient counselling.

Characterization of the craniofacial abnormalities of the homozygous G608G progeria mouse model

IntroductionHutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by premature aging, impacting multiple organ systems, including cardiovascular, musculoskeletal, and integumentary. Significant abnormalities in a transgenic mouse model (homozygous G608G mutation), specifically targeting the development of skull and facial bone indices through high-resolution CT scanning and cephalometric analysis.MethodsKey measurements include bone thickness, skull volume, and cranial suture integrity. Bone volume increased significantly in HGPS mice by 8 months of age compared to wildtype mice.ResultsCortical thickness showed a trend toward increased values in HGPS mice. Cranial metrics revealed distinct differences.DiscussionHGPS mice exhibited smaller internasal width, interzygomatic distance, and palatine length compared to WT mice over time.

Neuroscientific Approaches to Understanding Adolescent Susceptibility to Substance Abuse

Adolescence is a pivotal developmental stage characterised by significant neurobiological changes that heighten susceptibility to substance abuse. This period is marked by the maturation of the brain regions responsible for decision-making and impulse control, alongside an increased sensitivity to rewards driven by dopaminergic pathways. This review aimed to understand adolescent susceptibility to substance abuse using a neuroscientific approach. In line with best practices, data were collected from a variety reliable source to ensure a comprehensive view of the topic. Research studies on adolescent neurodevelopment have contributed to a broader understanding of the physiological and psychological factors at play during adolescence, while grey literature, including expert interviews and focused group discussions, has offered practical insights from frontline professionals, such as psychologists, social workers, and healthcare providers, who deal directly with adolescent substance use. These results demonstrate that the relationship between genetic factors and environmental conditions, such as stress and trauma, intensifies this vulnerability, thereby heightening the likelihood of individuals participating in risky behaviours. This review examines the neuroscientific foundations of substance use during adolescence, highlighting the critical role of timely interventions that utilize neuroplasticity to enhance resilience and reduce risk. By integrating cognitive training and behavioural therapies into public health initiatives, adolescents' cognitive control mechanisms and their propensity for substance abuse can be reduced.

Closing gaps in care and knowledge for adults with complex genetic conditions.

Closing gaps in care and knowledge for adults with complex genetic conditions.

Motor phenotypes associated with genetic neurodevelopmental disorders.

There is a growing number of monogenic disorders implicated in neurodevelopmental disorders (NDDs), including autism spectrum disorder and intellectual disability. Motor impairment is frequently seen in these disorders, although not clearly defined. We aimed to characterize the motor phenotype of genetic NDDs. We analyzed data from Simons Searchlight, collecting information on patients with genetic NDDs. Data analyzed included Vineland Adaptive Behavior Scales Second Edition (Vineland-II) motor standard scores, motor milestones and tone abnormalities. In total, 959 patients with 57 genetic disorders were included. Disorders associated with Vineland-II motor standard score <56 included GRIN2B-related disorder (mean standard score = 53.5), HNRNPH2-related disorder (mean standard score = 55.8) and SCN2A-related disorder (mean standard score = 49.9). The only genetic condition with a mean age of sitting unsupported ≥18 months was GRIN1-related disorder (mean age = 26.3 months). Genetic conditions with a mean age of walking independently ≥36 months included CTNNB1-related disorder (mean age = 37.4 months) and HNRNPH2-related disorder (mean age = 41.9 months). Tone abnormalities included hypotonia in 83% (577/696), hypertonia in 16% (112/696), a diagnosis of cerebral palsy (CP) in 10% (73/696) and a diagnosis specifically of spastic CP in 3% (23/696). Patients with genetic NDDs have a spectrum of motor impairment, which warrant further characterization.

Pediatric Diffuse Lung Disease in Infants: Imaging Findings and Histopathologic Correlation.

Childhood interstitial lung disease (chILD) encompasses a diverse group of genetic, infectious, and inflammatory conditions affecting infants and children. The recognition and understanding of these entities have highlighted the necessity for more accurate classification. This group of rare heterogeneous diseases comprises more than 200 different conditions and has a combined estimated prevalence of less than one patient per 100 000 children. Hence, a systematic diagnostic approach is crucial. This article describes a diagnostic approach for pediatric diffuse lung diseases in infancy, including an analysis of clinical presentations and imaging and histologic features to effectively distinguish among various chILD entities. Although they often have overlapping and nonspecific radiologic features, some chILD entities may exhibit typical imaging findings, resulting in a CT diagnosis or aiding in narrowing the differential diagnosis, thus guiding the clinician to the appropriate genetic tests, potentially limiting unnecessary biopsies. This approach aims to enhance the understanding and diagnosis of chILD in infants, thereby facilitating improved patient care.