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Frontiers in Physiology 2021Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal... (Review)
Review
Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.
PubMed: 34938205
DOI: 10.3389/fphys.2021.788411 -
Indian Journal of Orthopaedics May 2011Congenital insensitivity to pain and anhidrosis (CIPA) is a rare reported entity characterised by disturbance in the pain and temperature perception due to involvement...
Congenital insensitivity to pain and anhidrosis (CIPA) is a rare reported entity characterised by disturbance in the pain and temperature perception due to involvement of the autonomic and sensory nervous system. It is an autosomal recessive trait with several defects of the gene NTRK1 coding for the neurotrophic tyrosine kinase - a nerve growth factor receptor on chromosome 1q21-q22. Traumatic fractures are common and, because of lack of pain, may go unrecognised for prolonged periods, resulting in nonunion or pseudoarthrosis. A Charcot joint may be the end result. Treatment complications are very common in these patients and range from infection to wound breakdown to failure of fixation. We report here a rare case of CIPA in a 9-year-old girl and her younger male sibling with generalised absence of pain, anhidrosis and its orthopaedic implications.
PubMed: 21559108
DOI: 10.4103/0019-5413.80047 -
Acta Dermato-venereologica Aug 2022
Topics: Alopecia; Humans; Hypohidrosis; Nail Diseases; Nails, Malformed; Propylthiouracil
PubMed: 35971830
DOI: 10.2340/actadv.v102.2690 -
Journal of Medical Genetics Nov 1987
Review
Topics: Ectodermal Dysplasia; Genetic Linkage; Humans; Hypohidrosis; Infant; Phenotype; Sex Chromosome Aberrations; X Chromosome
PubMed: 3323518
DOI: 10.1136/jmg.24.11.659 -
Archives of Plastic Surgery Jan 2016
PubMed: 26848454
DOI: 10.5999/aps.2016.43.1.95 -
Movement Disorders : Official Journal... Mar 2017The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to...
BACKGROUND
The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes.
METHODS
All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing.
RESULTS
The majority of the 232 patients were MSA-parkinsonism (145, 63%). Initial postganglionic sudomotor testing was abnormal in 59%, whereas thermoregulatory sweat test was abnormal in 95% of all patients. MSA-parkinsonism patients were more likely to have an abnormal thermoregulatory sweat test compared with MSA-cerebellar (98% versus 90%, P = 0.006) and had a higher mean percentage of anhidrosis (57%) compared with MSA-cerebellar (48%; P = 0.033). Common anhidrosis patterns were regional (38%) and global (35%). The site of the lesion was preganglionic in 47% and mixed (preganglionic and postganglionic) in 41%. The increase in anhidrosis per year was 6.2% based on 70 repeat thermoregulatory sweat tests performed on 29 patients. The frequency of postganglionic sudomotor abnormalities increased over time.
CONCLUSIONS
Our findings suggest: (1) sudomotor dysfunction is almost invariably present in MSA and even more common and severe in MSA-parkinsonism than MSA-cerebellar; (2) a preganglionic pattern of sweat loss is common in MSA; however, pre- and postganglionic abnormalities may coexist; and (3) the increasing frequency of postganglionic sudomotor dysfunction over time suggests involvement of postganglionic fibers or sweat glands later in the disease course. © 2016 International Parkinson and Movement Disorder Society.
Topics: Aged; Autonomic Nervous System Diseases; Cerebellar Diseases; Female; Humans; Hypohidrosis; Male; Middle Aged; Multiple System Atrophy; Parkinsonian Disorders
PubMed: 27859565
DOI: 10.1002/mds.26864 -
Cureus Oct 2023Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin,...
Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin, hair, tooth, nail, and sweat glands. ED has two types hypohidrotic or anhidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. We report this case of classical hypohidrotic ectodermal dysplasia (HED) with clubbing. The association of clubbing with HED is still rare. This case report aims to discuss the etiology, clinical manifestations, and management of ectodermal dysplasia. A multidisciplinary approach is required including dentists, nutritionists, dermatologists, and physicians to manage ectodermal dysplasia.
PubMed: 37927739
DOI: 10.7759/cureus.46530 -
The European Journal of Neuroscience Feb 2014Although nerve growth factor (NGF) is a well-known neurotrophic factor, it also acts as a mediator of pain, itch and inflammation. Congenital insensitivity to pain with... (Review)
Review
Although nerve growth factor (NGF) is a well-known neurotrophic factor, it also acts as a mediator of pain, itch and inflammation. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder caused by loss-of-function mutations in NTRK1, the gene encoding a receptor tyrosine kinase for NGF, TrkA. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons in otherwise intact systems. NGF-dependent primary afferents are thinly myelinated Aδ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF-dependent primary afferents and sympathetic postganglionic neurons, respectively. These peripheral neurons form an interface between the nervous system and the 'body-proper' and play essential roles in the interoception and sympathetic regulation of various tissues or organs. Patients with CIPA also show mental retardation and characteristic behaviors and are probably neuron-deficient within the brain. However, the functions of NGF-dependent neurons in the brain are controversial, both in animal and in human studies. This review focuses on various brain regions that express TrkA mRNA, based on data from the Allen Human Brain Atlas, and discusses putative neuronal networks related to these brain regions in humans. A better understanding the distribution of NGF-dependent neurons in the brain will provide a framework for further studies to investigate pain, interoception and emotional responses. Furthermore, strategies targeting the molecular mechanisms through which the NGF-TrkA system functions may provide hope for the development of novel analgesics.
Topics: Animals; Brain; Emotions; Hereditary Sensory and Autonomic Neuropathies; Humans; Nerve Growth Factor; Nerve Net; Neuralgia; Receptor, trkA; Sensory Receptor Cells
PubMed: 24494678
DOI: 10.1111/ejn.12448 -
Hand (New York, N.Y.) Jan 2022Congenital insensitivity to pain is a rare autosomal recessive condition characterized by insensitivity to painful stimuli due to absence of sensory and sympathetic...
Congenital insensitivity to pain is a rare autosomal recessive condition characterized by insensitivity to painful stimuli due to absence of sensory and sympathetic post ganglionic neurons in the skin and skeletal system leading to lack of protective sensation and altered joint propioception. This study was performed to assess hand and wrist manifestations of patients with congenital insensitivity to pain in the Maltese Islands. Records of public and private hospitals were reviewed to identify patients suffering from this condition. A review of notes, patients, and imaging was performed. A Disabilities of the Arm, Shoulder, and Hand score was obtained to assess level of function. Nine patients were identified. Mean age of diagnosis was 8.9 years. Interphalangeal joints were most commonly affected. Multiple spontaneous or posttraumatic fingertip ulceration occurred in 5 patients. Anhidrosis resulted in more protracted ulcers and infections, requiring amputation of distal and middle phalanges due to osteomyelitis. The wrist joint was less commonly involved and showed more complex joint involvement. The hand and wrist are involved in different ways, with fingertip ulceration leading to potential infection and osteomyelitis in the hand, whereas the wrist joint is involved in cases of increased axial loading and load transfer, such as following prolonged use of walking and mobility aids. The latter should be borne in mind during management of lower limb conditions. Hand care and hygiene is important in all patients, especially in cases of anhidrosis due to the increased rate of ulceration and osteomyelitis requiring surgical intervention. Despite the severity of the condition, patients report good overall function.
Topics: Child; Hereditary Sensory and Autonomic Neuropathies; Humans; Hypohidrosis; Pain Insensitivity, Congenital; Wrist; Wrist Joint
PubMed: 32141314
DOI: 10.1177/1558944720906556