“…Olmstedt syndrome is a genetic disease [127,128] that presents with sharply confined hyperkeratotic plaques on the palms and soles. The plaques are also found around the mouth and on the eyelids [129]. Other clinical findings include flexion deformities of the fingers, localized alopecia and leukokeratosis of the tongue [129].…”
Section: Olmstedt Syndromementioning
confidence: 99%
“…The plaques are also found around the mouth and on the eyelids [129]. Other clinical findings include flexion deformities of the fingers, localized alopecia and leukokeratosis of the tongue [129]. The clinical symptoms are variable but typically severe and disabling [130].…”
Regular keratinocyte differentiation is crucial for the formation of an intact epidermal barrier and is triggered by extracellular calcium. Disturbances of epidermal barrier formation and aberrant keratinocyte differentiation are involved in the pathophysiology of several skin diseases, such as psoriasis, atopic dermatitis, basal and squamous skin cancer, and genetic skin diseases such as Darier's disease and Olmstedt syndrome. In this review, we summarize current knowledge about the underlying molecular mechanisms of calcium-induced differentiation in keratinocytes. We provide an overview of calcium's genomic and non-genomic mechanisms to induce differentiation and discuss the calcium gradient in the epidermis, giving rise to cornified skin and lipid envelope formation. We focus on the calcium-sensing receptor, transient receptor potential channels, and STIM/Orai as the major constituents of calcium sensing and calcium entry in the keratinocytes. Finally, skin diseases linked to impaired differentiation will be discussed, paying special attention to disturbed TRP channel expression and TRP channel mutations.
“…Olmstedt syndrome is a genetic disease [127,128] that presents with sharply confined hyperkeratotic plaques on the palms and soles. The plaques are also found around the mouth and on the eyelids [129]. Other clinical findings include flexion deformities of the fingers, localized alopecia and leukokeratosis of the tongue [129].…”
Section: Olmstedt Syndromementioning
confidence: 99%
“…The plaques are also found around the mouth and on the eyelids [129]. Other clinical findings include flexion deformities of the fingers, localized alopecia and leukokeratosis of the tongue [129]. The clinical symptoms are variable but typically severe and disabling [130].…”
Regular keratinocyte differentiation is crucial for the formation of an intact epidermal barrier and is triggered by extracellular calcium. Disturbances of epidermal barrier formation and aberrant keratinocyte differentiation are involved in the pathophysiology of several skin diseases, such as psoriasis, atopic dermatitis, basal and squamous skin cancer, and genetic skin diseases such as Darier's disease and Olmstedt syndrome. In this review, we summarize current knowledge about the underlying molecular mechanisms of calcium-induced differentiation in keratinocytes. We provide an overview of calcium's genomic and non-genomic mechanisms to induce differentiation and discuss the calcium gradient in the epidermis, giving rise to cornified skin and lipid envelope formation. We focus on the calcium-sensing receptor, transient receptor potential channels, and STIM/Orai as the major constituents of calcium sensing and calcium entry in the keratinocytes. Finally, skin diseases linked to impaired differentiation will be discussed, paying special attention to disturbed TRP channel expression and TRP channel mutations.
“…Other patients are reported with nonperiorificial keratotic lesions involving the thighs, arms, elbows, knees and intertriginous folds. Hyperkeratotic linear streaks [ 45 , 52 ], follicular keratosis [ 40 ], pachyderma, cheilitis [ 47 ], ichthyotic lesions or chronic blepharitis [ 14 , 23 , 40 ] may be also observed. Figure 1 Clinical features.…”
Section: Reviewmentioning
confidence: 99%
“…The diagnosis of Olmsted syndrome is supported by clinical criteria that require the exclusion of other diseases. OS has to be differentiated from other severe forms of PPK, such as Vohwinkel syndrome (MIM#124500 and 604117, ORPHA494 and ORPHA79395), Mal de Meleda (MIM#248300, ORPHA87503), Clouston syndrome (MIM#129500, ORPHA189), Papillon-Lefèvre syndrome (MIM#245000, ORPHA678), pachyonychia congenita (MIM#167200 and 167210, ORPHA2309), Tyrosinemia type II (MIM#276600, ORPHA28378) and Haim-Munk syndrome (MIM#245010, ORPHA2342) (Table 2 ) [ 52 ]. The periorificial involvement is the unique characteristic of OS that allows exclusion of the above syndromes.…”
Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. The disease starts usually at birth or in early childhood. About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent. The most suggestive symptoms associate PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe. Most of reported OS cases are sporadic, although familial cases with different mode of inheritance were also described. Mutations in TRPV3 (Transient receptor potential vanilloid-3) gene have recently been identified as a cause of autosomal dominant (gain-of-function mutations) or recessive OS. Mutations in MBTPS2 (membrane-bound transcription factor protease, site 2) gene were identified in a recessive X-linked form. The diagnosis relies mainly on clinical features associating severe PPK and periorificial keratotic plaques, but can be challenging in patients with incomplete phenotype or atypical features. OS has to be differentiated from other severe forms of PPK including Vohwinkel, Clouston, Papillon-Lefèvre or Haim-Munk syndromes, Mal de Meleda, pachyonychia congenita, Tyrosinemia type II and acrodermatitis enteropathica. When differential diagnoses are difficult to exclude, genetic studies are essential to search for a TRPV3 or MBTPS2 mutation. However, additional genes remain to be identified. No specific and satisfactory therapy is currently available for OS. Current treatments of hyperkeratosis (mainly emollients, keratolytics, retinoids or corticosteroids), either topical or systemic, are symptomatic and offer only temporary partial relief. Specific management of pain and itching is important to reduce the morbidity of the disease. The disease is debilitating and progressive keratoderma and auto-amputation of digits can prevent patients from grasping and walking, and confine them to a wheelchair. New therapeutic options are therefore crucial and are expected from a better understanding of the disease mechanisms. The use of TRPV3 antagonists would represent such a targeted and potentially powerful strategy.
“…Other reported features include leukokeratosis of the tongue, icthyotic lesions, pain, itching, absent premolar teeth, hearing loss for high frequencies, sclerosing cholangitis, short stature, and laxity of the large joints, linear hyperkeratotic follicular streaks, and acral hyperhidrosis. [ 1 2 ] Hypotrichosis has rarely been reported in Olmsted syndrome.…”
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