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Orthokeratosis

MedGen UID:
375169
Concept ID:
C1843359
Finding
SNOMED CT: Orthokeratosis (708474007)
 
HPO: HP:0040162

Definition

Formation of an anuclear keratin layer [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOrthokeratosis

Conditions with this feature

Pityriasis rubra pilaris
MedGen UID:
45939
Concept ID:
C0032027
Disease or Syndrome
Pityriasis rubra pilaris is an uncommon skin disorder characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic, although up to 6.5% of PRP-affected individuals report a positive family history. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression: the disorder is usually present at birth or appears during the first years of life and is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema, with only a modest response to treatment (summary by Fuchs-Telem et al., 2012).
Child syndrome
MedGen UID:
82697
Concept ID:
C0265267
Disease or Syndrome
The NSDHL-related disorders include: CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males. CHILD syndrome is characterized by unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Nail changes are also common. The heart, lung, and kidneys can also be involved. CK syndrome (named for the initials of the original proband) is characterized by mild to severe cognitive impairment and behavior problems (aggression, attention deficit hyperactivity disorder, and irritability). All affected males reported have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis. Strabismus is common. Optic atrophy is also reported.
Odonto-onycho-dermal dysplasia
MedGen UID:
208666
Concept ID:
C0796093
Disease or Syndrome
Odontoonychodermal dysplasia (OODD) is an autosomal recessive disorder characterized by dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, hyperkeratosis of the palms and soles, hypo- and hyperhidrosis of the skin, and atrophic patches on the face (summary by Adaimy et al., 2007; Yu et al., 2019).
Punctate palmoplantar keratoderma type 1
MedGen UID:
372099
Concept ID:
C1835662
Disease or Syndrome
A very rare hereditary skin disease with manifestation of irregularly distributed epidermal hyperkeratosis of the palms and soles. Reported in 35 families worldwide to date. The lesions usually start to develop in early adolescence but can also present later in life. Mutations in the AAGAB gene (15q22.33-q23) have recently been identified as one of the causes. Mutations in the COL14A1 gene (8q23) have also been identified as causal in some cases in Asia that seem to have a similar phenotype
Neonatal ichthyosis-sclerosing cholangitis syndrome
MedGen UID:
334382
Concept ID:
C1843355
Disease or Syndrome
A very rare complex ichthyosis syndrome with characteristics of scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. The ichthyosis presents with diffuse white scales sparing the skin folds and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly and biochemical cholestasis. Caused by a mutation in the CLDN1 gene on chromosome 3q28 coding for the tight junction protein claudin-1. Autosomal recessive pattern of inheritance.
Annular epidermolytic ichthyosis
MedGen UID:
334410
Concept ID:
C1843463
Disease or Syndrome
A rare clinical variant of epidermolytic ichthyosis, with manifestations of blistering phenotype at birth and the development from early infancy of annular polycyclic erythematous scales on the trunk and extremities. It has been reported in less than 10 families. The disease is caused by mutations in the KRT1 (12q11-q13) and KRT10 (17q21-q23) genes, encoding keratins 1 and 10 respectively. These mutations impair keratin filament formation and weaken the structural stability of the keratinocyte cytoskeleton. Transmission is autosomal dominant.
Autosomal recessive congenital ichthyosis 5
MedGen UID:
347628
Concept ID:
C1858133
Disease or Syndrome
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
Loricrin keratoderma
MedGen UID:
395099
Concept ID:
C1858805
Disease or Syndrome
Variant Vohwinkel syndrome is a rare genodermatosis characterized by hyperkeratosis of the palms and soles, with a honeycomb appearance; constricting bands encircling the digits of the hands and feet, which frequently lead to autoamputation of the fifth digits; starfish-shaped, salmon-colored hyperkeratotic lesions, or knuckle pads, on the dorsal surface of the hands; and ichthyosiform dermatosis. The pathognomonic histologic finding is markedly thickened stratum corneum, hypergranulosis, and particularly, hyperkeratosis with round nuclei retained in the stratum corneum. Unlike classic Vohwinkel syndrome, hearing loss is not a feature (summary by Maestrini et al., 1996).
Autosomal recessive congenital ichthyosis 6
MedGen UID:
436851
Concept ID:
C2677065
Disease or Syndrome
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
Autosomal recessive congenital ichthyosis 8
MedGen UID:
765943
Concept ID:
C3553029
Disease or Syndrome
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
Autosomal recessive congenital ichthyosis 9
MedGen UID:
767263
Concept ID:
C3554349
Disease or Syndrome
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
Severe dermatitis-multiple allergies-metabolic wasting syndrome
MedGen UID:
816049
Concept ID:
C3809719
Disease or Syndrome
A rare genetic epidermal disorder with characteristics of congenital erythroderma with severe psoriasiform dermatitis, ichthyosis, severe palmoplantar keratoderma, yellow keratosis on the hands and feet, elevated immunoglobulin E, multiple food allergies, and metabolic wasting. Other variable features may include hypotrichosis, nail dystrophy, recurrent infections, mild global developmental delay, eosinophilia, nystagmus, growth impairment and cardiac defects.
Hypopigmentation-punctate palmoplantar keratoderma syndrome
MedGen UID:
816111
Concept ID:
C3809781
Disease or Syndrome
Cole disease (COLED) is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013).
Peeling skin syndrome 4
MedGen UID:
895692
Concept ID:
C4225407
Disease or Syndrome
Any peeling skin syndrome in which the cause of the disease is a mutation in the CSTA gene.
Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type
MedGen UID:
934583
Concept ID:
C4310616
Disease or Syndrome
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).
Erythrokeratodermia variabilis et progressiva 3
MedGen UID:
1380593
Concept ID:
C4479619
Disease or Syndrome
Erythrokeratodermia variabilis et progressiva is a rare skin disease. Patients with EKVP3 have normal skin at birth but develop hyperpigmentation and scaling at sites of friction in childhood, with progression to near-confluent corrugated hyperkeratosis, palmoplantar keratoderma, and transient figurate erythema (summary by Boyden et al., 2015). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200).
Peeling skin syndrome 6
MedGen UID:
1648406
Concept ID:
C4748093
Disease or Syndrome
Peeling skin syndrome-6 (PSS6) is characterized by generalized ichthyotic dry skin and bullous peeling lesions on the trunk and limbs at sites of minor trauma. There is residual hyperpigmentation in areas of healing, but no scarring. Skin symptoms are exacerbated by warmth and humidity; however, the disorder improves markedly with age (Bolling et al., 2018; Mohamad et al., 2018). For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).
Olmsted syndrome 1
MedGen UID:
1778121
Concept ID:
C5542829
Disease or Syndrome
Olmsted syndrome-1 (OLMS1) is a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques with severe pruritus of lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas (summary by Lin et al., 2012). The digital constriction ('pseudoainhum') may progress to autoamputation of fingers and toes (Olmsted, 1927). Genetic Heterogeneity of Olmsted Syndrome Olmsted syndrome-2 (OLMS2; 619208) is caused by mutation in the PERP gene (609301) on chromosome 6q23. An X-linked form of Olmsted syndrome (OLMSX; 300918) is caused by mutation in the MBTPS2 gene (300294) on chromosome Xp22.
Ichthyosis, annular epidermolytic, 2
MedGen UID:
1824037
Concept ID:
C5774264
Disease or Syndrome
Annular epidermolytic ichthyosis-2 (AEI2) is characterized by erythema and blistering of skin at birth that improves without scarring, as well as palmoplantar keratoderma. Some patients experience intermittent severe flares of generalized annular and polycyclic erythematous scaling plaques (Sybert et al., 1999; Zaki et al., 2018). For a discussion of genetic heterogeneity of AEI, see AEI1 (607602).

Professional guidelines

PubMed

Joshi TP, Duvic M
Am J Clin Dermatol 2024 Mar;25(2):243-259. Epub 2023 Dec 30 doi: 10.1007/s40257-023-00836-x. PMID: 38159213
Abu Hashim II, Abo El-Magd NF, El-Sheakh AR, Hamed MF, Abd El-Gawad AEH
Int J Nanomedicine 2018;13:1059-1079. Epub 2018 Feb 20 doi: 10.2147/IJN.S156412. PMID: 29503541Free PMC Article
Klein A, Landthaler M, Karrer S
Am J Clin Dermatol 2010;11(3):157-70. doi: 10.2165/11530070-000000000-00000. PMID: 20184391

Recent clinical studies

Etiology

Joshi TP, Duvic M
Am J Clin Dermatol 2024 Mar;25(2):243-259. Epub 2023 Dec 30 doi: 10.1007/s40257-023-00836-x. PMID: 38159213
López Hurtado D, Delgado ME, Ortega Díaz J, Solís Avaca M, Carmona AIvarado H, Cabello Durán C
Rev Chil Pediatr 2020 Feb;91(1):94-98. Epub 2019 Dec 3 doi: 10.32641/rchped.v91i1.1168. PMID: 32730418
Ring NG, Craiglow BG, Panse G, Antaya RJ, Ashack K, Ashack R, Faith EF, Paller AS, McNiff JM, Choate KA, Ko CJ
J Cutan Pathol 2020 May;47(5):425-430. Epub 2019 Dec 26 doi: 10.1111/cup.13633. PMID: 31849081
Lallas A, Sgouros D, Zalaudek I, Tanaka M, Saida T, Thomas L, Kittler H, Kobayashi K, Koga H, Phan A, Longo C, Moscarella E, Katoulis A, Argenziano G
Melanoma Res 2014 Feb;24(1):83-7. doi: 10.1097/CMR.0000000000000037. PMID: 24276365
Abanmi AA, Al Zouman AY, Al Hussaini H, Al-Asmari A
Int J Dermatol 2002 Jul;41(7):411-4. doi: 10.1046/j.1365-4362.2002.01398.x. PMID: 12121556

Diagnosis

Balaban A, Al-Rohil RN
Am J Dermatopathol 2022 May 1;44(5):372-375. doi: 10.1097/DAD.0000000000002055. PMID: 35120035
Erdem O, Leblebici C, Koku Aksu AE, Erdil D, Kara Polat A, Gürel MS
J Cutan Pathol 2022 Jan;49(1):42-48. Epub 2021 Aug 8 doi: 10.1111/cup.14105. PMID: 34289144
López Hurtado D, Delgado ME, Ortega Díaz J, Solís Avaca M, Carmona AIvarado H, Cabello Durán C
Rev Chil Pediatr 2020 Feb;91(1):94-98. Epub 2019 Dec 3 doi: 10.32641/rchped.v91i1.1168. PMID: 32730418
Mu EW, Mir A, Meehan SA, Nguyen N
Dermatol Online J 2015 Dec 16;21(12) PMID: 26990327
Rizzo C, Bragg J, Soldano AC, Cohen D, Soter NA
Dermatol Online J 2008 May 15;14(5):3. PMID: 18627739

Therapy

Joshi TP, Duvic M
Am J Clin Dermatol 2024 Mar;25(2):243-259. Epub 2023 Dec 30 doi: 10.1007/s40257-023-00836-x. PMID: 38159213
Liu YA, Dai J, Nagarajan P, Torres-Cabala CA, Aung PP, Prieto VG, Cho WC
Am J Dermatopathol 2023 Mar 1;45(3):185-188. Epub 2023 Jan 10 doi: 10.1097/DAD.0000000000002369. PMID: 36626570
Erdem O, Leblebici C, Koku Aksu AE, Erdil D, Kara Polat A, Gürel MS
J Cutan Pathol 2022 Jan;49(1):42-48. Epub 2021 Aug 8 doi: 10.1111/cup.14105. PMID: 34289144
Ayhan E, Baykara SN, Ozekinci S, Aytekin S
Skinmed 2013 May-Jun;11(3):185-7. PMID: 23930362
Klein A, Landthaler M, Karrer S
Am J Clin Dermatol 2010;11(3):157-70. doi: 10.2165/11530070-000000000-00000. PMID: 20184391

Prognosis

Erdem O, Leblebici C, Koku Aksu AE, Erdil D, Kara Polat A, Gürel MS
J Cutan Pathol 2022 Jan;49(1):42-48. Epub 2021 Aug 8 doi: 10.1111/cup.14105. PMID: 34289144
López Hurtado D, Delgado ME, Ortega Díaz J, Solís Avaca M, Carmona AIvarado H, Cabello Durán C
Rev Chil Pediatr 2020 Feb;91(1):94-98. Epub 2019 Dec 3 doi: 10.32641/rchped.v91i1.1168. PMID: 32730418
Rivarola de Gutierrez E, Innocenti AC, Cippitelli MJ, Salomón S, Vargas-Roig LM
Med Oral Patol Oral Cir Bucal 2014 Jul 1;19(4):e359-65. doi: 10.4317/medoral.19289. PMID: 24608215Free PMC Article
Klein A, Landthaler M, Karrer S
Am J Clin Dermatol 2010;11(3):157-70. doi: 10.2165/11530070-000000000-00000. PMID: 20184391
Soeprono FF
Am J Dermatopathol 1986 Aug;8(4):277-83. doi: 10.1097/00000372-198608000-00001. PMID: 3766917

Clinical prediction guides

Balić A, Garces Rene J, Radoš J
Acta Dermatovenerol Croat 2022 Nov;30(3):191-193. PMID: 36812281
Chanprapaph K, Pomsoong C, Tankunakorn J, Eden C, Suchonwanit P, Rutnin S
Dermatology 2022;238(3):464-475. Epub 2021 Aug 11 doi: 10.1159/000517971. PMID: 34515092
Erdem O, Leblebici C, Koku Aksu AE, Erdil D, Kara Polat A, Gürel MS
J Cutan Pathol 2022 Jan;49(1):42-48. Epub 2021 Aug 8 doi: 10.1111/cup.14105. PMID: 34289144
López Hurtado D, Delgado ME, Ortega Díaz J, Solís Avaca M, Carmona AIvarado H, Cabello Durán C
Rev Chil Pediatr 2020 Feb;91(1):94-98. Epub 2019 Dec 3 doi: 10.32641/rchped.v91i1.1168. PMID: 32730418
Cunningham SR, Walsh M, Matthews R, Fulton R, Burrows D
J Am Acad Dermatol 1987 Jan;16(1 Pt 1):117-23. doi: 10.1016/s0190-9622(87)70011-5. PMID: 3805380

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