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Olmsted syndrome: clinical, molecular and therapeutic aspects.

Duchatelet S, Hovnanian A - Orphanet J Rare Dis (2015)

Bottom Line: Specific management of pain and itching is important to reduce the morbidity of the disease.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.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR 1163, Laboratory of Genetic skin diseases, Imagine Institute, 2nd floor, 24 bld du Montparnasse, 75015, Paris, France. sabine.duchatelet@inserm.fr.

ABSTRACT
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.

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Related in: MedlinePlus

Clinical features. A. Diffuse and transgredient, inflammatory plantar keratosis in a 2 year of age child. B. Periauricular keratosis in a 2 year of age child.
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Fig1: Clinical features. A. Diffuse and transgredient, inflammatory plantar keratosis in a 2 year of age child. B. Periauricular keratosis in a 2 year of age child.

Mentions: Initially, the hallmarks for the diagnosis of OS are bilateral mutilating palmoplantar keratoderma (Figure 1A) associated with periorificial keratotic plaques (mouth, nose, eyes, genital, anal, ears, navel) (Figure 1B) [1]. Indeed, progression of the keratoderma may lead to flexion deformities, constrictions of digital bands and even spontaneous digit amputations. However, this pseudoainhum feature is in fact inconsistently reported in OS patient [45]. In addition, in rare cases, periorificial keratotic plaques are absent [55,56]. Keratoderma is initially focal and distributed on the pressure points, gradually extends to most of the surface and becomes diffuse, massive and thicker with time with painful deep fissures. The keratotic lesions are pruritic and can be painful with pressure. Some cases present with focal or punctuate keratoderma [45,57]. A clear improvement of the keratoderma during febrile diseases may occur [19]. 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


Olmsted syndrome: clinical, molecular and therapeutic aspects.

Duchatelet S, Hovnanian A - Orphanet J Rare Dis (2015)

Clinical features. A. Diffuse and transgredient, inflammatory plantar keratosis in a 2 year of age child. B. Periauricular keratosis in a 2 year of age child.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4373112&req=5

Fig1: Clinical features. A. Diffuse and transgredient, inflammatory plantar keratosis in a 2 year of age child. B. Periauricular keratosis in a 2 year of age child.
Mentions: Initially, the hallmarks for the diagnosis of OS are bilateral mutilating palmoplantar keratoderma (Figure 1A) associated with periorificial keratotic plaques (mouth, nose, eyes, genital, anal, ears, navel) (Figure 1B) [1]. Indeed, progression of the keratoderma may lead to flexion deformities, constrictions of digital bands and even spontaneous digit amputations. However, this pseudoainhum feature is in fact inconsistently reported in OS patient [45]. In addition, in rare cases, periorificial keratotic plaques are absent [55,56]. Keratoderma is initially focal and distributed on the pressure points, gradually extends to most of the surface and becomes diffuse, massive and thicker with time with painful deep fissures. The keratotic lesions are pruritic and can be painful with pressure. Some cases present with focal or punctuate keratoderma [45,57]. A clear improvement of the keratoderma during febrile diseases may occur [19]. 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

Bottom Line: Specific management of pain and itching is important to reduce the morbidity of the disease.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.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR 1163, Laboratory of Genetic skin diseases, Imagine Institute, 2nd floor, 24 bld du Montparnasse, 75015, Paris, France. sabine.duchatelet@inserm.fr.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus