INTRODUCTION — The ichthyoses, also called disorders of keratinization or disorders of cornification, are a heterogeneous group of disorders characterized by a generalized scaling of the skin of varying severity. The great majority of ichthyoses are inherited, but acquired forms can develop in the setting of malignancy, autoimmune or infectious disease, and nutritional deficiency.
The molecular basis and pathophysiology of most inherited ichthyoses has been clarified by the identification of causative mutations in over 50 genes encoding structural proteins or enzymes involved in a broad variety of cellular functions, from DNA repair to skin barrier homeostasis . Abnormalities in any of these components result in a rather stereotypic epidermal response with epidermal hyperplasia and the formation of excess stratum corneum accompanied by abnormal desquamation and visible accumulation of scales on the skin's surface .
This topic will review the major types of inherited ichthyoses, utilizing the consensus nomenclature adopted by the 2009 Ichthyosis Consensus Conference . Paraneoplastic ichthyosis is discussed separately. (See "Cutaneous manifestations of internal malignancy", section on 'Acquired ichthyosis'.)
EPIDEMIOLOGY — Ichthyosis vulgaris and X-linked ichthyosis are the most common types of ichthyosis, with an estimated incidence of 1 in 250 births and 1:6000 male births, respectively [3,4]. Autosomal recessive congenital ichthyoses, which include lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis, are rare; their overall incidence has been estimated at approximately 1 in 200,000 births .
STRUCTURE AND FUNCTION OF THE EPIDERMIS — The average adult skin surface area is 1.8 m2 and contains nearly 85 billion nucleated cells, requiring daily generation of three billion keratinocytes to achieve simple replacement [6,7]. This cellular demand is met by a population of keratinocyte stem cells that cycle slowly to generate the mitotically active cells of the basal layer of the epidermis, which enter into a pathway of terminal differentiation.
Regulated by precise temporal and spatial gene expression, keratinocyte differentiation results in a series of changes within an individual cell as it completes its approximately 28-day long course from the basal layer to stratum corneum. This cycle requires the synthesis of site-relevant proteins, including adhesion and structural proteins, and also of cholesterol and other components necessary for the generation of the lipid barrier.
In the basal layer, cells produce extracellular matrix proteins that ensure strong adhesion to the underlying dermis and also synthesize basal-layer specific keratins 5 and 14, which are members of a family of intermediate filaments responsible for keratinocyte structural integrity. With progression to the spinous layer, cells cease dividing and begin expressing a series of differentiation-specific proteins. These include new keratins 1 and 10, as well as the building blocks for a lipid-based barrier (ie, glucosylceramides, phospholipids, and free sterols) packaged into specialized organelles known as lamellar bodies . In the granular layer, additional protein components necessary for the generation of an extensively cross-linked cornified envelope are synthesized and packaged into keratohyalin granules.
In the transition from granular layer to stratum corneum, keratinocytes enter into the cornification pathway, in which the cell becomes anucleate and enzymatic crosslinks are formed between structural proteins (eg, involucrin, loricrin, envoplakin) and keratin intermediate filament network. At this stage, a lipid envelope is extruded into the intercellular space from lamellar bodies to form lipid sheets composed of ceramides, cholesterol, and free fatty acids . This process leads to the generation of a lipid-rich stratum corneum consisting primarily of corneocytes, which are flat, polyhedral, anucleate cells composed of crosslinked protein. Through incompletely understood pathways that involve the action of proteases, corneocyte adhesion is modified, permitting desquamation at the surface of the epidermis .
CLASSIFICATION — The 2009 consensus classification, based upon the clinical phenotype, mode of inheritance, and molecular defect, recognizes two main groups of ichthyoses: nonsyndromic forms, in which the phenotypic expression of the disorder is seen only in the skin; and syndromic forms, in which other organs or systems are involved (table 1A-B) . (See 'Nonsyndromic inherited ichthyoses' below and 'Syndromic ichthyoses' below.)
NONSYNDROMIC INHERITED ICHTHYOSES
Ichthyosis vulgaris — Ichthyosis vulgaris (MIM #146700) is the most common form of inherited ichthyosis. It is caused by loss of function mutations in the filaggrin gene (FLG) and is inherited in an autosomal semi-dominant fashion with incomplete penetrance [11,12]. Individuals with one mutated allele have a mild phenotype, whereas those with mutations in both manifest severe disease. Histologically, ichthyosis vulgaris is characterized by a reduction of keratohyalin granules or absence of the granular layer.
Clinical findings include fine white to gray scaling which is most prominent on the abdomen and extensor surfaces of the extremities, with sparing of the flexures and face (picture 1A-C). The palms and soles show increased skin markings or hyperlinearity (picture 2). Keratosis pilaris (keratotic elevations around the hair follicles), most prominent on the upper arms and legs, is present in many patients. There is a marked seasonal variation in severity, with improvement in warm and sunny weather with high degree of ambient humidity and worsening in dry and cold weather. Ichthyosis vulgaris is associated with an increased risk for atopy, including asthma, allergies, and atopic dermatitis [13,14].
Treatment with emollients, humectants, and/or keratolytics is typically sufficient to ameliorate symptoms.
Recessive X-linked ichthyosis — Recessive X-linked ichthyosis (XLI, MIM #308100) typically affects male offspring who inherit an X chromosome bearing a mutated gene from their asymptomatic carrier mother. Recessive XLI is caused by mutations in the STS gene on Xp22.3, encoding steroid sulfatase, which hydrolyzes sulfate esters, including cholesterol sulfate and sulfated steroid hormones. In most cases, mutations are complete gene deletions, whereas simple point mutations occur in approximately 10 percent of cases. Rarely, deletions extend to adjacent genes and lead to contiguous gene syndromes. (See 'Contiguous gene syndromes' below.)
Recessive XLI presents with generalized peeling in the neonatal period (picture 3A) and fine scaling on the trunk and extremities in infancy and childhood (picture 3B). Over time, scales become more platelike and adherent with a brownish hue. The popliteal and antecubital fossae and central face are spared, but the axillae and lateral neck are often involved (picture 3C). Frequently, recessive XLI is clinically indistinguishable from ichthyosis vulgaris.
Asymptomatic corneal opacities in Descemet's membrane occur in approximately 50 percent of adult patients and up to 25 percent of asymptomatic carriers . Children with recessive XLI may have an increased risk of cryptorchidism and an increased risk of testicular cancer unrelated to undescended testis [16-18].
The diagnosis, differential diagnosis, and management of recessive XLI are discussed in detail elsewhere. (See "Recessive X-linked ichthyosis".)
Autosomal recessive congenital ichthyosis — Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of nonsyndromic disorders of keratinization, which includes lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE), and harlequin ichthyosis (HI). Of these disorders, HI is the most clinically distinct and genetically homogeneous entity, resulting from loss of function mutations in ABCA12. In contrast, LI and CIE represent a spectrum of disorders due to mutations in TGM1 (MIM #190195), ALOX12B (MIM #603741), ALOXE3 (MIM #607206), NIPAL4 (MIM #609383), CYP4F22 (MIM #611495), ABCA12 (MIM #607800), PNPLA1 (MIM #612121), CERS3 (MIM #615276), SDR9C7 (MIM #609767), SULT2B1 (MIM #604125), and other yet unidentified genes. No clear genotype-phenotype correlation has been possible in these disorders, since mutation in the same genes may present with widely divergent phenotypes. (See "Autosomal recessive congenital ichthyosis".)
Lamellar ichthyosis and congenital ichthyosiform erythroderma — Although initially considered separate entities, lamellar ichthyosis (LI, MIM #242300) and congenital ichthyosiform erythroderma (CIE, MIM #242100) show clinical and genetic overlap . Most cases are caused by mutations in one of several genes, including TGM1, NIPAL4, ALOX12B, ALOXE3, ABCA12, PNPLA1, ASPRV1, and CYP4F22 [19-22].
LI and CIE typically present at birth with a collodion membrane (picture 4), a tight translucent membrane covering the newborn's body that sheds in the first few weeks of life with emollient application. In LI, the collodion membrane is replaced by thick hyperkeratosis with dark, plate-like adherent scales (picture 5). Ectropion is prominent and palmoplantar keratoderma (thickening of the palms and soles) of varying severity is usually present. The hyperkeratosis may impair the sweat gland function, resulting in hypohidrosis. In CIE, scaling tends to be milder than in LI, with variable erythroderma and ectropion.
Early management is centered on supportive care, including prevention of infection, management of hydration and nutrition, and ophthalmologic care . Emollients are the mainstay of treatment to control scaling and improve the skin barrier function. Topical retinoids can be useful in reducing scale in localized areas.
For severe scaling, oral retinoids, such as acitretin and isotretinoin, are an important therapeutic option. Oral retinoids are known teratogens. Appropriate counseling and contraception must be given to women of childbearing age. In addition, the consequences of long-term or lifelong therapy must also be weighed. Adverse effects of long-term retinoid therapy include premature closure of the epiphyses, calcification of tendons and ligaments, development of skeletal hyperostosis, and osteoporosis [24-26]. (See "Autosomal recessive congenital ichthyosis", section on 'Lamellar ichthyosis phenotype'.)
Harlequin ichthyosis — Harlequin ichthyosis (HI; MIM #242500) is a severe disorder of keratinization caused by loss of function mutations in ABCA12; less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation [27,28]. ABCA12 is an ATP binding cassette (ABC) transporter, and is a member of a large family of proteins that hydrolyze ATP to transport cargo across membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier .
Newborns with HI present with thick, fissured armor-plate hyperkeratosis, severe ectropion (eversion of the eyelids), eclabium (eversion of the lips), and malformation of the auricle (picture 6). Early complications result from infection due to fissuring of the hyperkeratotic plates and respiratory distress due to physical restriction of chest wall expansion.
Management includes supportive care and treatment of hyperkeratosis and skin barrier dysfunction. Intubation is often required until nares are patent. Nutritional support with tube feeds is essential until eclabium resolves and infants can begin nursing. Ophthalmology consultation can be helpful in the early management of ectropion, which is initially pronounced and resolves as scale is shed. Liberal application of petrolatum is performed multiple times daily. To avoid digital ischemia, careful debridement of constrictive bands of hyperkeratosis should be performed.
Prior reports suggest that the mortality rate in the neonatal period is approximately 50 percent, and many infants with HI die shortly after birth, but improved neonatal intensive care and early treatment with oral retinoids may improve survival . Children who survive the neonatal period usually evolve to a less severe phenotype, resembling a severe congenital ichthyosiform erythroderma. (See "Autosomal recessive congenital ichthyosis", section on 'Harlequin ichthyosis phenotype'.)
Minor variants — Minor variants of ARCI include self-healing (self-improving) collodion baby and bathing suit ichthyosis.
Self-healing collodion baby — Collodion baby is the presenting phenotype of several nonsyndromic and syndromic congenital disorders of keratinization such as lamellar ichthyosis, nonbullous congenital ichthyosiform erythroderma, Sjögren-Larsson syndrome, and trichothiodystrophy (table 2). The collodion membrane usually sheds in the first few weeks of life and the transition to the definitive phenotype occur. The terms "self-healing collodion baby" and "self-improving collodion baby" refer to children presenting with a collodion membrane at birth who subsequently show a normal or nearly normal skin upon shedding of the collodion membrane [31,32]. This condition appears to be caused by mutations in ALOX12B, ALOXE3, CYP4F22, and TGM1 genes [33-36]. A localized form called "acral self-healing collodion baby" also has been described .
Bathing suit ichthyosis — Bathing suit ichthyosis is a rare variant of lamellar ichthyosis characterized by scaling mainly limited to the trunk and warmer areas of the skin [37-40]. It is caused by an autosomal recessive missense mutation in TGM1, resulting in transglutaminase temperature sensitivity [38,40-43].
Keratinopathic ichthyoses — The keratinopathic ichthyoses are a group of rare cornification disorders caused by mutations in one of the keratin genes, resulting in abnormalities of the keratin intermediate filaments, a component of the keratinocyte cell cytoskeleton. They encompass a spectrum of clinical phenotypes of varying severity, including epidermolytic ichthyosis, superficial epidermolytic ichthyosis, annular epidermolytic ichthyosis, ichthyosis Curth-Macklin, and ichthyosis with confetti.
The keratinopathic ichthyoses are discussed separately. (See "Keratinopathic ichthyoses".)
SYNDROMIC ICHTHYOSES — Inherited ichthyoses may present as syndromic diseases with involvement of the skin and other organs or systems (table 1B) [1,44].
Contiguous gene syndromes — Deletions in the steroid sulfatase gene on Xp22.3 that extend to adjacent genes lead to contiguous gene syndromes, which may have an X-linked recessive or dominant mode of inheritance. One example is Kallmann syndrome (MIM #308700), a heterogeneous group of disorders characterized by hypogonadotropic hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency, anosmia, a variety of neurologic defects, and, in some cases, linked ichthyosis [45,46]. (See "Recessive X-linked ichthyosis", section on 'Contiguous gene syndromes' and "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)".)
X-linked dominant disorders — Mutations occurring on the X chromosome, which cause severe phenotypes in males, appear in a mosaic fashion in females due to patterns of X-chromosome inactivation. These include:
●CHILD syndrome – CHILD syndrome (MIM #308050) is a rare X-linked dominant disorder that is usually lethal in males during gestation and thus affects almost exclusively females. CHILD syndrome is characterized by congenital hemidysplasia, ichthyosiform erythroderma, and limb defects. It is caused by reduced-function mutations in either the NAD(P) dependent steroid dehydrogenase-like (NSDHL) gene or occasionally the EBP gene . The skin involvement is unilateral, with a sharp midline demarcation, and consists of circumscribed linear plaques covered by prominent wax-like scales (picture 7). The heart, lung, and kidneys can also be involved.
●Conradi-Hünermann-Happle syndrome – Congenital X-linked dominant chondrodysplasia punctata type 2 (MIM #302960), also called Conradi-Hünermann-Happle syndrome, is a disorder caused by mutations in the EBP gene, encoding the delta-8 delta-7 sterol isomerase emopamil-binding protein. It occurs in a mosaic pattern in females and presents at birth as a congenital ichthyosiform erythroderma that clears over months and is replaced by linear hyperkeratosis, follicular atrophoderma, and pigmentary abnormalities . Stippled calcifications are seen in radiographs of areas of endochondral bone formation during childhood and usually resolve by adulthood. Other clinical findings include short stature, rhizomelic shortening of the limbs, craniofacial defects, and cataracts.
Ichthyoses with hair abnormalities
Netherton syndrome — Netherton syndrome (NS; MIM #256500) is an autosomal recessive disorder caused by mutations in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI) . It presents at birth with a generalized erythroderma covered by fine scales, a specific hair shaft abnormality called trichorrhexis invaginata or "bamboo hair," and atopic manifestations (picture 8A-C). Elevated serum levels of IgE and failure to thrive in the first years of life are also common. (See "Netherton syndrome".)
Trichothiodystrophy — Trichothiodystrophy (MIM #601675), also called ichthyosiform erythroderma with hair abnormality, developmental delay, and growth retardation, is a heterogeneous group of disorders characterized by sulfur-deficient brittle hair with hair-shaft abnormalities (eg, trichoschisis (picture 9), trichorrhexis nodosa, ribboning) (picture 10). (See "Autosomal recessive congenital ichthyosis", section on 'Trichothiodystrophy' and "Evaluation and diagnosis of hair loss", section on 'Inherited and acquired structural hair disorders'.)
Most patients have mutations in the ERCC2/XPD gene on chromosome 19q13.2-q13.3, encoding the basal transcription/DNA repair factor IIH . Clinical features include photosensitivity, ichthyosis, intellectual impairment, short stature, cataracts, and dystrophic nails.
Ichthyoses with neurologic involvement
Multiple sulfatase deficiency — Multiple sulfatase deficiency (MIM #272200) is a rare autosomal recessive disorder caused by deficiency of all lysosomal and microsomal sulfatase enzymes . Infants present with features of recessive X-linked ichthyosis and a variable combination of features of mucopolysaccharidosis type II, IIIA, IIID, IVA, VI, or metachromatic leukodystrophy. (See "Mucopolysaccharidoses: Clinical features and diagnosis" and "Metachromatic leukodystrophy".)
Sjögren-Larsson syndrome — Sjögren-Larsson syndrome (MIM #270200) is a rare autosomal recessive condition caused by mutations in the ALDH3A2 gene that encodes the enzyme fatty aldehyde dehydrogenase. It presents with congenital ichthyosis, spastic diplegia, and mild to moderate developmental delay. (See "Sjögren-Larsson syndrome".)
Refsum disease — Refsum disease (MIM 266500) is a very rare autosomal recessive neurocutaneous disorder caused by mutations in the PHYX gene encoding phytanoyl-CoA hydroxylase, which result in plasma and tissue accumulation of phytanic acid . Clinical symptoms may develop from infancy to adulthood and include progressive retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, sensorineural deafness, ichthyosis, anosmia, and cardiac conduction defects. (See "Neuropathies associated with hereditary disorders", section on 'Refsum disease'.)
Gaucher disease type 2 — Gaucher disease is an inborn error of metabolism caused by mutations in the glucocerebrosidase gene GBA. Type 2, the infantile cerebral type, is characterized by a nearly complete loss of glucocerebrosidase activity, hepatosplenomegaly, and progressive neurologic signs, including opisthotonus, swallowing impairment, and seizures. Some but not all newborns present as collodion babies . (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Type 2 (GD2)'.)
Ichthyoses with other associated symptoms
KID syndrome — Keratitis-ichthyosis-deafness (KID) syndrome (MIM #148210) is a rare autosomal dominant disorder caused by heterozygous mutations in the GJB2 gene, encoding connexin 26, a beta-type gap junction protein [53,54]. It presents at birth with generalized erythroderma and variable degree of scaling and leathery skin (picture 11). Older children have thick, erythrodermic plaques that are dry and scaly anywhere on the body but especially around the flexures, elbows, and knees; keratotic, hyperplastic, and inflammatory nodules on the scalp, face, trunk, and lower legs; and palmoplantar keratoderma (picture 12A-B) (see "Palmoplantar keratoderma", section on 'Palmoplantar keratodermas with deafness'). In situ and invasive squamous cell carcinoma arising within these dysplastic lesions have been reported in several patients with KID syndrome during adolescence and adulthood . Other manifestations include hearing impairment, in most cases of sensorineural origin, and ocular involvement, including reduced visual acuity resulting from keratitis, corneal neovascularization, and corneal abrasion/ulceration .
Neutral lipid storage disease — Neutral lipid storage disease (MIM #275630), also called Chanarin-Dorfman syndrome is an autosomal recessive disorder characterized by accumulation of triglycerides in the cytoplasm of leukocytes, muscle, liver, fibroblasts, and other tissues. It is caused by mutations in the ABHD5, encoding abhydrolase domain containing 5, an enzyme involved in long-chain fatty acid oxidation. Affected newborns are either collodion babies or erythrodermic. The skin involvement evolves to a mild to moderate nonbullous ichthyosiform erythroderma with fine, white scale on an erythematous background and lamellar scaling on the trunk. (See "Autosomal recessive congenital ichthyosis", section on 'Neutral lipid storage disease' and "Metabolic myopathies caused by disorders of lipid and purine metabolism", section on 'Neutral lipid storage diseases'.)
Ichthyosis prematurity syndrome — Ichthyosis prematurity syndrome (MIM #608649) is caused by mutations in the FATP4 gene, encoding the fatty acid transporter protein 4, involved in the translocation of long-chain fatty acids across the plasma membrane. It presents at birth with erythrodermic skin covered by a greasy, thick vernix caseosa-like scale that resolves rapidly into a mild chronic pruritic ichthyosis .
DIAGNOSTIC APPROACH — The diagnosis of ichthyosis is based upon the integration of the following :
●Skin phenotype (eg, scale pattern, quality, and color; presence of a collodion membrane at birth; presence of erythroderma; erosions or blistering)
●Time of onset and evolution over time
●Family history and apparent inheritance mode
●Histopathologic findings on skin biopsy
●Associated cutaneous manifestations (eg, blisters, photosensitivity, hair abnormalities)
●Presence or absence of associated extracutaneous manifestations
Genetic testing may be helpful for confirmation of diagnosis and genetic counseling. The decision to test should be guided by the clinical impression and the likelihood that a given mutation causes a suspected disorder. As an example, mutations in TGM1 cause approximately one-third of cases of autosomal recessive congenital ichthyosis, whereas most cases of epidermolytic ichthyosis result from mutations in KRT10 or KRT1. However, many disorders of keratinization present with complex phenotypes and a genotype-phenotype correlation is not always possible. Genetic diagnosis is particularly difficult in mild, sporadic cases.
In the United States, Clinical Laboratory Improvement Amendments (CLIA)-certified genetic testing is available from multiple providers, such as GeneDx (www.genedx.com). Information on CLIA-certified and research-based laboratories performing disease-specific genetic testing worldwide is available through the Genetic Testing Registry.
CARE OF THE NEONATE WITH A KERATINIZATION DISORDER — Many types of ichthyosis are undetectable in utero and present at birth or within the first several weeks of life. Dramatic presentations include harlequin ichthyosis, epidermolytic ichthyosis, and a group of disorders presenting at birth with a collodion membrane, which appears as a glistening translucent cellophane-like membrane covering the entire body (picture 4). (See 'Autosomal recessive congenital ichthyosis' above.)
Advances in neonatal intensive care have been central to improve the outcome of severe congenital ichthyoses, including those with high mortality rates such as harlequin ichthyosis. Newborn with keratinization disorders have a compromised barrier function, which is associated with increased transepidermal water loss, hypernatremic dehydration, and increased heat loss . These neonates are often managed in neonatal intensive care units. They should be placed in isolettes with increased humidity in the range of 50 to 70 percent and closely monitored for body temperature, vital signs, and electrolytes.
Increased metabolic demand due to more rapid epidermal turnover in hyperproliferative conditions requires caloric supplementation. Close monitoring for infection is mandatory. Bland emollients such as petrolatum should be applied regularly. They replace in part the barrier function, permit shedding of accumulated scale, and provide a proper environment for healing of fissures or erosions.
Early consultation with a multidisciplinary team is required in the most severe cases. The team should include a dermatologist, clinical geneticist, nutritionist, physical/occupational therapist, and social worker. A national patient support organization, the Foundation for Ichthyosis and Related Skin Types (FIRST, firstskinfoundation.org) enables medical consultations via a teledermatology program, facilitates contact between families with a newly diagnosed disorder of keratinization and other individuals/families with a similar disorder, and provides information for patients about such conditions.
SUMMARY AND RECOMMENDATIONS
●The inherited ichthyoses are a heterogeneous group of disorders characterized by generalized scaling of the skin of varying severity. Their molecular basis and pathophysiology has been clarified by the identification of causative mutations in over 50 genes encoding structural proteins or enzymes involved in the skin barrier homeostasis. (See 'Introduction' above.)
●The 2009 revised nomenclature and classification of inherited ichthyoses, based upon the clinical phenotype, mode of inheritance, and molecular defect, recognizes two main groups of ichthyoses: nonsyndromic (manifesting only in the skin) and syndromic (involving other organs or systems) forms (table 1A-B). (See 'Classification' above.)
●Nonsyndromic ichthyoses (table 1A) include common ichthyoses, such as ichthyosis vulgaris (picture 1A-C) and X-linked recessive ichthyosis (picture 3A-C). Rare and more severe types are lamellar ichthyosis (picture 5), congenital ichthyosiform erythroderma, harlequin ichthyosis, and epidermolytic ichthyosis (picture 13). (See 'Nonsyndromic inherited ichthyoses' above.)
●Syndromic ichthyoses (table 1B) may present with a wide range of extracutaneous manifestations, such as hypogonadotropic hypogonadism (eg, Kallmann syndrome), chondrodysplasia punctata (eg, Conradi-Hünermann-Happle syndrome), hair abnormalities (eg, Netherton syndrome), or neurologic involvement (eg, Sjögren-Larsson syndrome, Refsum disease). (See 'Syndromic ichthyoses' above.)
●The diagnosis of ichthyosis is based upon the integration of cutaneous findings, personal and family history, histopathologic findings, and presence of extracutaneous manifestations. Genetic testing may be helpful for confirmation of diagnosis and genetic counseling. (See 'Diagnostic approach' above.)
1 : Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009.
2 : Ichthyosis update: towards a function-driven model of pathogenesis of the disorders of cornification and the role of corneocyte proteins in these disorders.
13 : Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.
16 : Clinical spectrum of steroid sulfatase deficiency: X-linked recessive ichthyosis, birth complications and cryptorchidism.
21 : PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans.
26 : Retinoid hyperostosis. Skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis.
28 : ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.
29 : ABCA12 dysfunction causes a disorder in glucosylceramide accumulation during keratinocyte differentiation.
32 : Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation.
33 : Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients.
34 : Genotype-phenotype correlations with TGM1: clustering of mutations in the bathing suit ichthyosis and self-healing collodion baby variants of lamellar ichthyosis.
35 : Acral self-healing collodion baby: report of a new clinical phenotype caused by a novel TGM1 mutation.
36 : Two Cases of Autosomal Recessive Congenital Ichthyosis due to CYP4F22 Mutations: Expanding the Genotype of Self-Healing Collodion Baby.
38 : Specific TGM1 mutation profiles in bathing suit and self-improving collodion ichthyoses: phenotypic and genotypic data from 9 patients with dynamic phenotypes of autosomal recessive congenital ichthyosis.
40 : The South African "bathing suit ichthyosis" is a form of lamellar ichthyosis caused by a homozygous missense mutation, p.R315L, in transglutaminase 1.
41 : Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype.
45 : A new syndrome of anosmia, ichthyosis, hypogonadism, and various neurological manifestations with deficiency of steroid sulfatase and arylsulfatase C.
48 : Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.
51 : Natural disease history and characterisation of SUMF1 molecular defects in ten unrelated patients with multiple sulfatase deficiency.
53 : Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome.
54 : Keratitis-ichthyosis-deafness syndrome: A comprehensive review of cutaneous and systemic manifestations.
56 : Ichthyosis prematurity syndrome: clinical evaluation of 17 families with a rare disorder of lipid metabolism.
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