Orphanet J Rare Dis. 2024 Nov 29;19(1):446. doi: 10.1186/s13023-024-03377-6.

ABSTRACT

BACKGROUND: Rare disease (RD) management and orphan drug development in India face various hurdles regarding the implementation and adoption of comprehensive policies, lack of dedicated regulatory frameworks, and absence of epidemiological data. Current rare disease policy focuses more on strengthening the diagnostics and lacks a proper comprehensive treatment framework to ensure favorable clinical outcomes. Indian patients are largely excluded from global orphan drug clinical trials. This further alienates patients from access to rare disease treatment and available treatments come at high cost. This review-based study assesses the landscape of health policies and programs in India through a review of literature and guidelines, to identify strategic opportunities and recommendations for enhancing the overall care and support for the Rare Disease (RD) patient population and improving the orphan drug research ecosystem in India.

DISCUSSION: The absence of specific regulations, shortage of healthcare resources, budget constraints, competing health priorities, lack of patient data, and insufficient research incentives discourage orphan drug development and global clinical trial inclusion, resulting in treatment inaccessibility and high costs. The Indian Government introduced the National Policy for Treatment of Rare Diseases (NPRD) to address these challenges. Several initiatives have been introduced to attract stakeholders with government-funded research, grants, incentives, and accelerated regulatory approvals of novel therapies that can ensure timely prevention and treatment of rare diseases. The National RD Registry by the Indian Council of Medical Research (ICMR) aims to provide prevalence data. Innovative approaches are required to improve rare disease management and promote orphan drug research. This will ensure the accessibility and affordability of life-saving therapeutics for India's rare disease patients.

CONCLUSION: An integrated RD management and orphan drug research framework focusing on robust data management, patient-oriented policies to improve the treatment landscape, flexible regulations, strengthening rare disease registry with clinical and diagnostic data, and a favorable research ecosystem to promote indigenous research catering to the Indian population, will improve the treatment landscape and orphan drug research and development in India. This will ensure timely availability of therapeutics at affordable prices.

PMID:39614301 | DOI:10.1186/s13023-024-03377-6

Orphanet J Rare Dis. 2024 Nov 29;19(1):443. doi: 10.1186/s13023-024-03462-w.

ABSTRACT

BACKGROUND: Mass spectrometry-based quantitative proteomics has a demonstrated utility in increasing the diagnostic yield of mitochondrial disorders (MDs) and other rare diseases. However, for this technology to be widely adopted in routine clinical practice, it is crucial to accurately estimate delivery costs. Resource use and unit costs required to undertake a proteomics test were measured and categorized into consumables, equipment, and labor. Unit costs were aggregated to obtain a total cost per patient, reported in 2023 Australian dollars (AUD). Probabilistic and deterministic sensitivity analysis were conducted to evaluate parameter uncertainty and identify key cost drivers.

RESULTS: The mean cost of a proteomics test was $897 (US$ 607) per patient (95% CI: $734-$1,111). Labor comprised 53% of the total costs. At $342 (US$ 228) per patient, liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) was the most expensive non-salary component. An integrated analysis pipeline where all the standard analysis are performed automatically, as well as discounts or subsidized LC-MS/MS equipment or consumables can lower the cost per test.

CONCLUSIONS: Proteomics testing provide a lower-cost option and wider application compared to respiratory chain enzymology for mitochondrial disorders and potentially other functional assays in Australia. Our analysis suggests that streamlining and automating workflows can reduce labor costs. Using PBMC samples may be a cheaper and more efficient alternative to generating fibroblasts, although their use has not been extensively tested yet. Use of fibroblasts could potentially lower costs when fibroblasts are already available by avoiding the expense of isolating PBMCs. A joint evaluation of the health and economic implications of proteomics is now needed to support its introduction to routine clinical care.

PMID:39609890 | DOI:10.1186/s13023-024-03462-w

BMJ Open. 2024 Nov 27;14(11):e083044. doi: 10.1136/bmjopen-2023-083044.

ABSTRACT

INTRODUCTION: In 2020, the Australian Medical Services Advisory Committee (MSAC) recommended new proton beam therapy (PBT) item numbers be added to the Medicare Benefits Schedule. During the MSAC 1638 application process, MSAC recognised the uncertainties inherent in the cost-utility modelling of PBT. To address these uncertainties, MSAC proposed the establishment of a national registry with the intention to gather evidence to validate the claim of PBT's superior toxicity outcomes and cost-effectiveness compared with conventional photon radiation therapy.

METHODS AND ANALYSIS: The Australian Particle Therapy Clinical Quality Registry is a prospective, observational, longitudinal registry collecting national data on paediatric, adolescent young adult and adult patients with rare tumours receiving any form of radiation therapy for a defined group of diseases, specified by the MSAC 1638 Public Summary Document. Eligible patients undergoing radiation therapy at participating institutions will be provided with information about the registry, including the opt-out procedure. The registry has no enrolment cap and will persist either indefinitely or until the conclusion of the study.The study design was informed by the Australian Metadata Online Repository and contains a core set of minimum data elements. Representing baseline participant demographics, assessment, diagnosis and treatment; incorporating radiation and systemic therapies, with a specific focus on long-term follow-up, treatment toxicities and specific organ-at-risk testing.

ETHICS AND DISSEMINATION: There will be no identifying data used in any reports or presentations of data. Additionally, all identifiable data will be safeguarded according to standard practices and available only to the host institution submitting the data to the registry. Aggregated data for the purposes of research will be stripped of identifiers. The registry has been approved under the National Mutual Agreement by the Central Adelaide Local Health Network Human Research Ethics Committee-HREC: 2021/HRE00394.

TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000026729p.

PMID:39609005 | DOI:10.1136/bmjopen-2023-083044

Oncoimmunology. 2024 Dec 31;13(1):2432062. doi: 10.1080/2162402X.2024.2432062. Epub 2024 Nov 27.

ABSTRACT

Hairy cell leukemia variant (HCL-v) is a rare malignancy of clonal mature B-cells that follows a chronic disease course. HCL-v patients are often resistant to purine nucleoside analogs, which are the first-line therapy. To address the shortcomings of current therapy for HCL-v, we investigated the activity of a BAFF ligand-based CAR-T cell which binds to all three BAFF receptors, BAFF-receptor, TACI, and BCMA. Here, we demonstrate that HCLv patient-derived cells highly express all three BAFF receptors and that BAFF CAR-T cells induce significant cytotoxicity in vitro against both cell lines and HCL-v patient cells. This cytotoxicity corresponds with significant CAR-T cell activation, degranulation, and release of pro-inflammatory cytokines after co-incubation with HCLv cells. Furthermore, we successfully generated BAFF CAR-T cells directly from an HCLv patient and observed direct autologous killing against patient tumor cells in vitro. These HCLv patient-derived CAR-T cells were also effective in killing the Hair-M cell line and tumor cells derived from a different HCLv patient. Lastly, we also developed two mouse xenograft models for HCL, a subcutaneous Bonna-12 model and intravenous Hair-M xenograft model. We observed decreases in tumor burden and prolonged overall survival without significant toxicity. In conclusion, here we show that BAFF CAR-T cells exert anti-tumor effects in vitro and in vivo against multiple cell lines and patient-derived HCL-v samples and may be a successful therapeutic strategy for HCLv patients.

PMID:39604816 | DOI:10.1080/2162402X.2024.2432062

Exp Neurol. 2025 Feb;384:115073. doi: 10.1016/j.expneurol.2024.115073. Epub 2024 Nov 25.

ABSTRACT

Primary mitochondrial disorders (PMDs) are an extraordinarily complex group of rare disorders caused by impairment of the mitochondrial electron transport chain, or respiratory chain. Studying genotype-phenotype relationships in PMDs is a complex task. The clinical variability is large even in individuals with the same genotype, and the statistical power is low in single-center studies because of their rarity. To better define the clinical phenotypes associated with PMDs, in the last 15 years a significant multicenter effort has led to nation-wide studies on large cohorts of patients. Many national registries of mitochondrial patients have been developed in recent years, and now there is a strong effort towards international (and even global) registries. This review will revise the notable advances obtained with such studies in recent years, and will discuss the actual developments and future perspectives.

PMID:39603485 | DOI:10.1016/j.expneurol.2024.115073

J Pediatr. 2024 Nov 25:114422. doi: 10.1016/j.jpeds.2024.114422. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SOX17, a novel risk gene linked to heritable and congenital heart disease-associated PAH.

STUDY DESIGN: We assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing. Data were collected from registries and retrospective chart review.

RESULTS: We identified 13 children (8 female, 5 male) aged 1.6 to 16 years at diagnosis with SOX17 variants and PAH. Seven patients had atrial septal defects (ASD) and two had patent ductus arteriosus. At diagnostic cardiac catheterization, patients had severely elevated mean pulmonary artery pressure (mean 78, range 47-124 mmHg) and markedly elevated indexed pulmonary vascular resistance (mean 25.9, range 4.9-55 WU*m2). No patients responded to acute vasodilator testing. Catheter and CT angiography imaging demonstrated atypical pulmonary artery anatomy including severely dilated main pulmonary arteries, lack of tapering in third and fourth order pulmonary arteries, tortuous 'corkscrewing' pulmonary arteries, and abnormal capillary 'blush.' Several children had pulmonary artery stenoses and two had systemic arterial abnormalities. Histologic examination of explanted lungs from three patients disclosed plexiform arteriopathy and extensive aneurysmal dilation of alveolar septal capillaries.

CONCLUSIONS: SOX17-associated PAH is a distinctive genetic syndrome characterized by early onset severe PAH, extensive pulmonary vascular abnormalities, and high prevalence of congenital heart disease with intracardiac and interarterial shunts, suggesting a role for SOX17 in pulmonary vascular development.

PMID:39603521 | DOI:10.1016/j.jpeds.2024.114422

Mult Scler J Exp Transl Clin. 2024 Nov 26;10(4):20552173241293921. doi: 10.1177/20552173241293921. eCollection 2024 Oct-Dec.

ABSTRACT

BACKGROUND: The prevalence of multiple sclerosis (MS) in Latin America is generally considered low to moderate. However, accurate data regarding MS epidemiology in Colombia is lacking.

OBJECTIVE: This study aims to discuss the situation of MS in Colombia.

RESULTS: Analysis reveals a lack of accurate data regarding MS epidemiology in Colombia, however, there have been notable improvements in diagnosis and ultimately leading to better access to treatment for MS patients. While ethnic diversity may potentially influence MS prevalence, there is currently no strong data supporting this claim. MS treatment in Colombia, focuses on early disease-modifying therapy, nevertheless, MS is considered an orphan disease in Colombia, contributing to MS patients not receiving comprehensive evaluation in MS centers. Regional efforts are ongoing to improve diagnostic access and access to treatment for MS patients.

CONCLUSION: Despite the challenges in accurately defining MS epidemiology in Colombia, an increase in neurological training, diagnostic capabilities, and access to treatment has been observed. However, the status of MS as an orphan disease in Colombia poses challenges to comprehensive care for affected individuals. Further studies are needed to elucidate risk factors and improve care conditions for MS patients in the region.

PMID:39600996 | PMC:PMC11590136 | DOI:10.1177/20552173241293921

Orphanet J Rare Dis. 2024 Nov 26;19(1):438. doi: 10.1186/s13023-024-03429-x.

NO ABSTRACT

PMID:39593137 | DOI:10.1186/s13023-024-03429-x

Respir Res. 2024 Nov 26;25(1):416. doi: 10.1186/s12931-024-03040-5.

ABSTRACT

BACKGROUND: Pulmonary lymphangiomatosis (PL) is an ultrarare disease characterized by diffuse infiltration of the lung, pleura and/or mediastinum by abnormal lymphatic proliferation. Consented diagnostic or treatment approaches are not established. We therefore aimed to collect data on diagnostics and treatments in a cohort of patients with PL from a tertiary center for rare lung diseases.

METHODS: Clinical, radiological and outcome data from PL patients were collected retrospectively.

RESULTS: 12 patients were diagnosed between 1996 and 2022 in our center. PL was diagnosed more commonly in female (58%), never smokers (75%) and younger patients (mean age 42 years). Main clinical symptoms comprised haem- and chyloptysis (58%) and dyspnea on exertion (83%). Pulmonary function was mostly restrictive (mean VC 59%) with impaired DLCO (mean 65%). Radiological assessment mainly showed mediastinal involvement (83%), and pleural effusion (67%), pleural thickening (67%) and bronchial wall thickening (67%) while interstitial changes were rare. Diagnosis was confirmed by surgical or transbronchial cryobiopsy. 8 patients were treated with sirolimus, 3 of these combined with a surgical intervention and in one case surgical intervention was necessary 9 months after initiation of sirolimus. Clinical and radiological improvement was demonstrated for all patients treated with sirolimus. 1 patient received a lung transplant due disease progression. Survival rates were 90% after a mean follow up of at least 3 months.

CONCLUSION: This case series illustrates the variability of the clinical presentation of PL. Among our patients, those treated with sirolimus showed significant clinical, functional and radiological improvement. However, further investigation is needed to understand the pathogenesis of lymphangiomatosis in order to establish therapeutic approaches.

PMID:39593123 | DOI:10.1186/s12931-024-03040-5

J Ayub Med Coll Abbottabad. 2024 Jan-Mar;36(1):229-231. doi: 10.55519/JAMC-01-12868.

ABSTRACT

Scleredema Diabeticorum (SD) is a rare condition characterized by diffuse, symmetrical induration along with non-pitted swelling mostly on the upper back as a result of mucin being deposited in the dermis. It can also involve posterior neck, shoulders, and scalp. We report a case of 48 years old female patient from Pakistan, with uncontrolled diabetes mellites type 2 for the last 15 years, presenting with thickened skin at the back of the neck resulting in difficulty in neck and shoulder movements. This led to decreased functional class from I to II causing her to develop insomnia and depression. Scleredema diabeticorum is a difficult disease to manage as it runs a long and debilitating course with little propensity of remission with available treatments.

PMID:39585292 | DOI:10.55519/JAMC-01-12868

Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241300137. doi: 10.1177/03946320241300137.

ABSTRACT

Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis characterized by recurrent, painful ulcers that commonly affect the lower extremities but can also involve other parts of the body. Over half of patients with PG have concomitant systemic immune diseases, with the association of PG with systemic sclerosis (SSc) being extremely rare. Treatment of PG primarily involves local therapy, steroids, and immunosuppressants, with an increasing emphasis on biologic agents. Among these, tumor necrosis factor-alpha (TNF-α) antagonists are considered effective. The patient in this report was an elderly female with a history of systemic sclerosis for many years and initially presented with gangrenous ulcers on the fingertips. After inconclusive conventional treatment, adalimumab was added for 5 weeks, resulting in disease suppression, a reduction in ulcer size, and re-epithelialization of the skin lesions after 6 months.

PMID:39584543 | DOI:10.1177/03946320241300137

Mol Biol Rep. 2024 Nov 22;52(1):7. doi: 10.1007/s11033-024-10085-8.

ABSTRACT

BACKGROUND: Spinocerebellar ataxia with axonal neuropathy type 1 (OMIM: 607250) is an extremely rare autosomal recessive disorder caused by a mutation in the tyrosyl-DNA phosphodiesterase 1 (TDP1) gene. Only a single missense variant (p.His493Arg) in this gene has been reported. This variant was found in three Arab families with a possible common founder effect.

METHODS AND RESULTS: We report a female patient born to a consanguineous Pakistani family segregating autosomal recessive spinocerebellar ataxia with axonal neuropathy type 1. The patient presents additional clinical features distinct from previously reported Arab families including congenital onset of the disease. We performed whole exome sequencing with the patient's DNA and identified a novel missense variant (NC_000014.9:g.89991982C > T; p.His478Tyr) in exon 13 of the TDP1 gene. Sanger sequencing was performed to verify the autosomal recessive segregation of the p.His478Tyr variant in the family.

CONCLUSION: The current study expands both the clinical and mutation spectrum of the TDP1 associated spinocerebellar ataxia with axonal neuropathy type 1 and increases the body of evidence that supports the pathogenic role of TDP1 in cerebellar ataxias with peripheral neuropathy.

PMID:39576382 | DOI:10.1007/s11033-024-10085-8

Mo Med. 2024 Jul-Aug;121(4):284-288.

ABSTRACT

The world of genetic testing continues to evolve as new technologies provide insight into previously unchartered territories. Access to genetic testing, especially for complex medical patients, could potentially improve the lives of thousands of individuals with undiagnosed conditions. Barriers to testing include financial and physical limitations, along with the emotional and social fortitude that is at times needed for vulnerable populations to agree to testing and participation in research. As healthcare providers, it is imperative that we adopt a wholistic approach to care so that we can arm our patients with the necessary resources to navigate their medical journey.

PMID:39575078 | PMC:PMC11578571

Mo Med. 2024 Jul-Aug;121(4):304-309.

ABSTRACT

DeSanto-Shinawi (DESSH) syndrome is a rare autosomal dominant condition caused by pathogenic variants in the WAC gene. DESSH syndrome was first identified in 2015 in six patients, but has since been diagnosed in more than 200 individuals worldwide. Patients exhibit a variable degree of developmental delay (DD), intellectual disability (ID), hypotonia, gastrointestinal and eye abnormalities, epilepsy, behavioral difficulties, and recognizable facial features. In order to educate families and address the complex medical needs of the increasing number of patients with DESSH syndrome, we established a new multidisciplinary clinic at Washington University in St. Louis. The first clinic was held in September 2022 and attended by 15 patients and their families. Herein, we report the structure of the clinic and present the main clinical findings of these patients. This pilot experience highlights the utility of a multidisciplinary approach to evaluating individuals with rare genetic diseases and the value of collaborating with family support groups to establish multidisciplinary clinics for these disorders, and provides guidance for future clinic planning.

PMID:39575070 | PMC:PMC11578572

Clin Chem. 2025 Jan 3;71(1):169-184. doi: 10.1093/clinchem/hvae183.

ABSTRACT

BACKGROUND: Exome- or genome-based panels-also known as slices or virtual panels-are now a popular approach that involves comprehensive genomic sequencing while restricting analysis to subsets of genes based on patients' phenotypes. This flexible strategy enables frequent gene updates based on novel disease associations as well as reflexing to analyzing other genes up to the whole exome or genome. With recent improvements addressing limitations associated with virtual panels, the advantages of this approach, relative to static custom-based panels, remain to be systematically characterized.

METHODS: Here we perform slice testing on 1014 patients (50.5% females; average age 17 years) referred from multiple pediatric clinics within a single center in the Middle East (83% Arab population).

RESULTS: Initial analysis uncovered molecular diagnoses for 235 patients for a diagnostic yield of 23% (235/1014). "On the fly" focused analysis in most negative cases (N = 779) identified clinically significant variants correlating with patients' presentations in genes outside the originally ordered panel for another 35 patients (3.5% or 35/1024) increasing the overall diagnostic yield to 27%. The pathogenic variants underlying the additional cases (13% of all positive cases) were excluded from the original "panel" gene list, mainly as result of issues related to panel selection, novel gene-disease associations, phenotype spectrum broadening, or gene lists variability. The additional findings led to changes in clinical management in most patients (94%).

CONCLUSIONS: Our findings support slice testing as an efficient and flexible platform that facilitates updates to gene lists to achieve high clinical sensitivity and utility.

PMID:39569808 | DOI:10.1093/clinchem/hvae183

J Pediatr Ophthalmol Strabismus. 2024 Nov-Dec;61(6):e59-e62. doi: 10.3928/01913913-20240911-01. Epub 2024 Nov 1.

ABSTRACT

The authors report a case of a 66-year-old man with sudden-onset diplopia and redness in the left eye. The examination revealed left hypotropia with exotropia and limited elevation. Contrast-enhanced computed tomography and histopathology suggested inferior rectus myositis with fibrosis. The patient was treated with steroid pulse therapy, followed by slow tapering. Later, the patient underwent surgical strabismus correction. He remained diplopia-free with an excellent cosmetic outcome and minimal elevation deficit 12 months postoperatively. [J Pediatr Ophthalmol Strabismus. 2024;61(6):e59-e62.].

PMID:39569718 | DOI:10.3928/01913913-20240911-01

Nature. 2024 Dec;636(8042):404-411. doi: 10.1038/s41586-024-08217-y. Epub 2024 Nov 20.

ABSTRACT

Although rare neurodevelopmental conditions have a large Mendelian component1, common genetic variants also contribute to risk2,3. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family environment4 also play a role. Here we addressed these questions using genetic data from 11,573 patients with rare neurodevelopmental conditions, 9,128 of their parents and 26,869 controls. Common variants explained around 10% of variance in risk. Patients with a monogenic diagnosis had significantly less polygenic risk than those without, supporting a liability threshold model5. A polygenic score for neurodevelopmental conditions showed only a direct genetic effect. By contrast, polygenic scores for educational attainment and cognitive performance showed no direct genetic effect, but the non-transmitted alleles in the parents were correlated with the child's risk, potentially due to indirect genetic effects and/or parental assortment for these traits4. Indeed, as expected under parental assortment, we show that common variant predisposition for neurodevelopmental conditions is correlated with the rare variant component of risk. These findings indicate that future studies should investigate the possible role and nature of indirect genetic effects on rare neurodevelopmental conditions, and consider the contribution of common and rare variants simultaneously when studying cognition-related phenotypes.

PMID:39567701 | DOI:10.1038/s41586-024-08217-y

Sci Rep. 2024 Nov 20;14(1):28780. doi: 10.1038/s41598-024-79872-4.

ABSTRACT

In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two. Singleton WES facilitated the diagnostic process in the Czech undiagnosed pediatric population. We believe it is an effective approach to enable appropriate counseling, surveillance, and personalized clinical management.

PMID:39567597 | DOI:10.1038/s41598-024-79872-4

Soc Sci Med. 2024 Dec;363:117380. doi: 10.1016/j.socscimed.2024.117380. Epub 2024 Nov 18.

ABSTRACT

This article sets out to explore the dilemmas present in the reproductive practices of people affected by rare hereditary diseases, focusing on the use of diagnostic tests and the practice of genetic counselling in Brazil. The development of technologies capable of mapping 'genetic flaws' prior to conception or in prenatal consultations has led researchers to consider how these technologies may be shaping contemporary subjectivities related to kinship and guiding reproductive decisions based on knowledge of our 'genetic heritage.' Genetic counselling has emerged in this setting as a modality of health knowledge and information capable of assisting people, especially women, in their reproductive choices. In Brazil, access to these technologies and their use has proven to be unequal and heterogeneous. I argue that the idea of 'choice' that permeates genetic counselling needs to be problematized by considering the social, cultural, economic, affective and moral frameworks in which women are inserted and that inform and/or determine their reproductive decisions. Based on this premise, I analyse how families 'at risk' of rare hereditary diseases deal with the idea of 'genetic inheritance' in relation to the 'wish to have children', and the impasses surrounding the idea of 'informed choice' when we evaluate this rhetoric in the context of the shortfalls in access to healthcare and the limits to reproductive justice in Brazil.

PMID:39561432 | DOI:10.1016/j.socscimed.2024.117380

Neurology. 2024 Dec 24;103(12):e210070. doi: 10.1212/WNL.0000000000210070. Epub 2024 Nov 19.

ABSTRACT

Macroglossia can be seen in multiple conditions, but its evaluation becomes more challenging when approached as an isolated presenting symptom. This is a case of a 65-year-old patient with isolated progressive tongue hypertrophy of unclear etiology for 5 years. We navigate the causes of macroglossia and discuss the clinical and diagnostic procedures that helped us narrow the differential diagnoses for our patient. We emphasize searching for evidence of more systemic involvement and the use of appropriate genetic testing to change the course of the disease and avoid therapeutic delay.

PMID:39561306 | DOI:10.1212/WNL.0000000000210070