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Molecular Genetics & Genomic Medicine Apr 2024Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene,... (Review)
Review
BACKGROUND
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability.
METHODS
Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.
RESULTS
CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3-8 years). Two patients exhibited self-mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851-33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574-156_850+1113del (exons 5-7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851-33T>A (p.?) mutations and compound heterozygous for c.851-33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574-156_850+1113del (exons 5-7 del) displayed a late onset and milder clinical manifestation.
CONCLUSION
All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Channelopathies; Hereditary Sensory and Autonomic Neuropathies; Hypohidrosis; Indoles; Intellectual Disability; Pain; Pain Insensitivity, Congenital; Propionates
PubMed: 38581121
DOI: 10.1002/mgg3.2430 -
Cureus Feb 2024Horner's syndrome is a rare condition that results when there is an interruption of the sympathetic fibers that run from the stellate ganglion to the eye. The classic...
Horner's syndrome is a rare condition that results when there is an interruption of the sympathetic fibers that run from the stellate ganglion to the eye. The classic triad of Horner's syndrome includes unilateral ptosis, miosis, and anhidrosis. Spontaneous pneumothorax is a rare condition that occurs when there is a sudden collapsed lung without any direct cause. A few cases have been reported of spontaneous pneumothorax associated with iatrogenic Horner's syndrome. A chest thoracostomy is a procedure that can lead to iatrogenic Horner's syndrome. Here, we present the case of a 25-year-old male with a left-sided spontaneous pneumothorax complicated by iatrogenic Horner's syndrome secondary to chest thoracostomy.
PubMed: 38550474
DOI: 10.7759/cureus.55033 -
JAMA Dermatology May 2024Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features....
IMPORTANCE
Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias.
OBJECTIVE
To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023.
RESULTS
The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants.
CONCLUSIONS AND RELEVANCE
The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.
Topics: Humans; Denmark; Ectodermal Dysplasia; Prevalence; Female; Male; Child; Registries; Adolescent; Adult; Young Adult; Cohort Studies; Child, Preschool; Middle Aged
PubMed: 38477886
DOI: 10.1001/jamadermatol.2024.0036 -
Practical Neurology Mar 2024
PubMed: 38471756
DOI: 10.1136/pn-2023-004038 -
Kyobu Geka. the Japanese Journal of... Feb 2024A ganglioneuroma is a rare, benign, neurogenic tumor originating from the sympathetic ganglion. Mediastinal ganglioneuroma are mostly detected in children, typically...
A ganglioneuroma is a rare, benign, neurogenic tumor originating from the sympathetic ganglion. Mediastinal ganglioneuroma are mostly detected in children, typically around 10 years of age, and are rarely identified in adults. Herein, we report two surgically resected cases of mediastinal ganglioneuroma in adults. In Case 1, a 53-year-old man, without any symptom, underwent a computed tomography, revealing a 3.2 cm well-defined paravertebral superior mediastinal tumor with long craniocaudal axis. In case 2, a 29-year-old woman presented with newly-developed ptosis and a history of left-sided facial hypohidrosis since the age of 10. Chest computed tomography (CT) revealed a 7.8 cm well-defined paravertebral superior mediastinal tumor with long craniocaudal axis. Both patients were initially suspected to have neurogenic tumors, particularly schwannomas. They underwent mediastinal tumor resections, requiring sympathetic nerve trunk dissection. Pathological examination confirmed the diagnosis of ganglioneuromas in both cases. Mediastinal ganglioneuroma must be differentiated from schwannoma, the most common neurogenic tumor in adults. Unlike schwannoma, ganglioneuroma cannot be enucleated, therefore attention should be focused on complications associated with sympathetic nerve trunk dissection, such as Horner's syndrome, hyperhidrosis, and arrhythmia. Identifying this rare entity and its characteristic imaging aids in preoperative differentiation, strategizing surgical approaches, and predicting complications.
Topics: Adult; Male; Female; Child; Humans; Middle Aged; Mediastinal Neoplasms; Ganglioneuroma; Tomography, X-Ray Computed; Neurilemmoma; Mediastinum
PubMed: 38459861
DOI: No ID Found -
Journal of Critical Care Jun 2024The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO...
PURPOSE
The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different pCO-levels. The purpose of this study was to compare two variants of pCO-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination.
MATERIALS AND METHODS
Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in pCO-levels were analysed for both variants.
RESULTS
At the start of AT, median pCO-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median pCO-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, pCO-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, pCO-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002).
CONCLUSIONS
Simultaneous pCO-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.
Topics: Humans; Male; Middle Aged; Female; Brain Death; Extracorporeal Membrane Oxygenation; Carbon Dioxide; Autonomic Nervous System Diseases; Flushing; Hypohidrosis
PubMed: 38395004
DOI: 10.1016/j.jcrc.2024.154545 -
Brain : a Journal of Neurology Feb 2024We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for...
We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.
PubMed: 38366572
DOI: 10.1093/brain/awae033 -
Clinical Medicine (London, England) Jan 2024
Topics: Humans; Hypohidrosis
PubMed: 38350407
DOI: 10.1016/j.clinme.2023.100009 -
Journal of the European Academy of... Jan 2024Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow-up of the temperature changes are rarely done in dermatology. The recent... (Review)
Review
Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow-up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost-effective thermography devices has made the implementation of thermography in clinical settings feasible. The aim of this scoping review is to summarize the evidence around the value and pitfalls of infrared thermography (IRT) when used in the dermatology clinic. A systematic literature search was done for original articles using IRT in skin disorders. The results concerning the potential of IRT for diagnosis, severity staging and monitoring of skin diseases were collected. The data on the sensitivity and specificity of IRT were extracted. Numerous studies have investigated IRT in various skin diseases, revealing its significant value in wound management, skin infections (e.g. cellulitis), vascular abnormalities and deep skin inflammation (e.g. hidradenitis suppurativa). For other dermatological applications such as the interpretation of intradermal and patch allergy testing, hyper-/anhidrosis, erythromelalgia, cold urticaria and lymph node metastases more complex calculations, provocation tests or active cooling procedures are required. Dermatologists should be aware of a learning curve of IRT and recognize factors contributing to false positive and false negative results. Nonetheless, enough evidence is available to recommend IRT as a supplement to the clinical evaluation for the diagnosis, severity and follow-up of several skin diseases.
PubMed: 38251780
DOI: 10.1111/jdv.19796