History

X-linked ichthyosis (XLI) is seen at birth or in the immediate neonatal period. Most typically, X-linked ichthyosis appears in infancy with scaling on the posterior neck, upper trunk, and extensor surfaces of the extremities.^[3]The scalp is often involved. In childhood, the boy who is affected has a "dirty-face" appearance, with an increase in involvement with age.

Atypical X-linked ichthyosis may be associated with a large deletion involving the steroid sulfatase (STS) gene.^[23]One patient has been described with scaling limited to the lower extremities as the sole manifestation. Men with X-linked ichthyosis disease-causing deletions appear to be at increased risk of cardiac arrhythmias and self-reported mood problems, the latter attributed to an altered basal ganglia structure.^[24]

Physical Examination

Adherent brown scaling is evident in a widespread distribution that often produces a dirty-face appearance, as shown in the images below.

Man with preauricular brownish scaling typical of X-linked ichthyosis.

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Dirty scale in X-linked ichthyosis.

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In early childhood, scaling of the scalp, preauricular skin, and posterior neck may be prominent. Flexures may be involved, but palms and soles are usually spared. Polygonal or "dirty" scaling is typically noted. However, a 2015 study documented children in whom the diagnosis was made incidentally by chromosomal microassay that showed mild phenotypes, sometimes strongly resembling simple mild dermatitis.^[25]

As the child ages, the mild scaling evident in the first few days of life becomes more evident and assumes a dirty yellow or brown color with dark, polygonal, firmly adherent scales.^[26]This generalized eruption tends to fade on the head but becomes more prominent on the trunk and extremities, particularly on the extensor surfaces of the legs. Scaling has a tendency to be more noticeable in cold and dry weather, improving in the summer months. It may rarely be first evident as erythroderma.^[27]

Hair and nails are normal in X-linked ichthyosis.

Corneal opacities may be evident with slit-lamp examination both of adult males who are affected and of women who are carriers.^[28]Biomicroscopy may show Meibomian gland dysfunction and stromal corneal opacities.^[29]The coma-shaped opacities in the posterior stroma are common findings.^[30]Ingordo and associates^[22]2003 assessment of the frequency of X-linked ichthyosis in a large representative sample of the Italian male population revealed that 4 (26.6%) of 15 patients had corneal opacities. No other significant associated changes were noted. Approximately 10% of males who are affected and female carriers have diffuse deposits in the posterior capsule or corneal stroma that does not affect vision. Subepithelial stromal keratopathies or epithelial irregularities are seen uncommonly in X-linked ichthyosis. Unique superficial corneal changes have been seen in one patient.

Cryptorchidism occurs in 20% of patients. A few cases of testicular cancer have developed in patients with X-linked ichthyosis and cryptorchidism.

Central nervous system electroencephalographic changes have been noted in a few patients.

STS deficiency slows the delivery of an infant because of insufficient cervical dilation. A relative failure occurs in the response to intravenous oxytocin. Since both are indications for cesarean delivery or forceps delivery, an increased perinatal morbidity and mortality may occur.

Syndromes of genetic contiguity have been described. As a result of broader chromosomal deletions, they may have X-linked ichthyosis and additional phenotypical abnormalities, which include short stature, chondrodysplasia punctata, mental retardation, and Kallmann syndrome (hypogonadotrophic hypogonadism).

The enzyme steroid sulfatase is normally expressed in the brain, a deficiency of which perhaps accounting for personality differences and an increased risk of psychopathology in affected individuals and female carriers.^[31]There is reportedly an association between X-linked ichthyosis and attention deficit hyperactivity disorder and motor disabilities.^{[11, 32]}

Differential Diagnoses

Wells RS, Kerr CB. Genetic classification of ichthyosis. Arch Dermatol. 1965 Jul. 92(1):1-6. [QxMD MEDLINE Link].
Brcic L, Wren GH, Underwood JFG, et al. Comorbid Medical Issues in X-Linked Ichthyosis. JID Innov. 2022 May. 2 (3):100109. [QxMD MEDLINE Link]. [Full Text].
Fernandes NF, Janniger CK, Schwartz RA. X-linked ichthyosis: an oculocutaneous genodermatosis. J Am Acad Dermatol. 2010 Mar. 62(3):480-5. [QxMD MEDLINE Link].
Süßmuth K, Traupe H, Metze D, Oji V. Ichthyoses in everyday practice: management of a rare group of diseases. J Dtsch Dermatol Ges. 2020 Mar. 18 (3):225-243. [QxMD MEDLINE Link].
Elias PM, Crumrine D, Rassner U, et al. Basis for abnormal desquamation and permeability barrier dysfunction in RXLI. J Invest Dermatol. 2004 Feb. 122(2):314-9. [QxMD MEDLINE Link].
Ramesh R, Bouloux P, Dorkins HR, Ellis R, Buch M, Batta K. Oral 4, X-linked ichthyosis with a contiguous gene defect in three successive generations. Br J Dermatol. 2007 Jun. 156(6):1404.
Elias PM, Williams ML, Choi EH, Feingold KR. Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis. Biochim Biophys Acta. 2014 Mar. 1841(3):353-61. [QxMD MEDLINE Link]. [Full Text].
Goodwin G, Hawley PP, Miller DT. A Case of HDR Syndrome and Ichthyosis: Dual Diagnosis by Whole-Genome Sequencing of Novel Mutations in GATA3 and STS Genes. J Clin Endocrinol Metab. 2016 Mar. 101 (3):837-40. [QxMD MEDLINE Link].
Zhang Q, Si N, Liu Y, Zhang D, Wang R, Zhang Y, et al. Steroid sulfatase and filaggrin mutations in a boy with severe ichthyosis, elevated serum IgE level and moyamoya syndrome. Gene. 2017 Jul 11. [QxMD MEDLINE Link].
Süßmuth K, Gruber R, Rodriguez E, Traupe H, Amler S, Sánchez-Guijo A, et al. Increased Prevalence of Filaggrin Deficiency in 51 Patients with Recessive X-Linked Ichthyosis Presenting for Dermatological Examination. J Invest Dermatol. 2018 Mar. 138 (3):709-711. [QxMD MEDLINE Link].
Diociaiuti A, Angioni A, Pisaneschi E, Alesi V, Zambruno G, Novelli A, et al. X-linked ichthyosis: clinical and molecular findings in 35 Italian patients. Exp Dermatol. 2018 Apr 19. [QxMD MEDLINE Link].
Huang Y, Luo S, Zhao P, Tan L, Fu G, Zhou A, et al. A novel STS mutation and an Xp22.31 microdeletion in a Chinese family with X-linked ichthyosis. Clin Exp Dermatol. 2021 Apr. 46 (3):614-617. [QxMD MEDLINE Link].
Sugawara T, Shimizu H, Hoshi N, Fujimoto Y, Nakajima A, Fujimoto S. PCR diagnosis of X-linked ichthyosis: identification of a novel mutation (E560P) of the steroid sulfatase gene. Hum Mutat. 2000 Mar. 15(3):296. [QxMD MEDLINE Link].
Ghosh D. Mutations in X-linked ichthyosis disrupt the active site structure of estrone/DHEA sulfatase. Biochim Biophys Acta. 2004 Dec 24. 1739(1):1-4. [QxMD MEDLINE Link].
Ghosh D. Three-dimensional structures of sulfatases. Methods Enzymol. 2005. 400:273-93. [QxMD MEDLINE Link].
Hosomi N, Oiso N, Fukai K, Hanada K, Fujita H, Ishii M. Deletion of distal promoter of VCXA in a patient with X-linked ichthyosis associated with borderline mental retardation. J Dermatol Sci. 2007 Jan. 45(1):31-6. [QxMD MEDLINE Link].
Canueto J, Ciria S, Hernandez-Martin A, Unamuno P, Gonzalez-Sarmiento R. Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. J Eur Acad Dermatol Venereol. 2010 Mar 4. [QxMD MEDLINE Link].
Canueto J, Ciria S, Hernandez-Martin A, et al. Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. J Eur Acad Dermatol Venereol. 2010 Oct. 24(10):1226-9. [QxMD MEDLINE Link].
Winge MC, Hoppe T, Lieden A, et al. Novel point mutation in the STS gene in a patient with X-linked recessive ichthyosis. J Dermatol Sci. 2011 Apr 7. [QxMD MEDLINE Link].
Toral-Lopez J, Gonzalez-Huerta LM, Cuevas-Covarrubias SA. Segregation analysis in X-linked ichthyosis: paternal transmission of the affected X-chromosome. Br J Dermatol. 2008 Apr. 158(4):818-20. [QxMD MEDLINE Link].
Craig WY, Roberson M, Palomaki GE, Shackleton CH, Marcos J, Haddow JE. Prevalence of steroid sulfatase deficiency in California according to race and ethnicity. Prenat Diagn. 2010 Sep. 30(9):893-8. [QxMD MEDLINE Link].
Ingordo V, D'Andria G, Gentile C, Decuzzi M, Mascia E, Naldi L. Frequency of X-linked ichthyosis in coastal southern Italy: a study on a representative sample of a young male population. Dermatology. 2003. 207(2):148-50. [QxMD MEDLINE Link].
Gonzalez-Huerta L, Mendiola-Jimenez J, Del Moral-Stevenel M, Rivera-Vega M, Cuevas-Covarrubias S. Atypical X-linked ichthyosis in a patient with a large deletion involving the steroid sulfatase (STS) gene. Int J Dermatol. 2009 Feb. 48(2):142-4. [QxMD MEDLINE Link].
Brcic L, Underwood JF, Kendall KM, Caseras X, Kirov G, Davies W. Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank. J Med Genet. 2020 Mar 5. [QxMD MEDLINE Link].
Hand JL, Runke CK, Hodge JC. The phenotype spectrum of X-linked ichthyosis identified by chromosomal microarray. J Am Acad Dermatol. 2015 Apr. 72 (4):617-27. [QxMD MEDLINE Link].
Xie W, Zhou H, Zhou L, Gong Y, Lin J, Chen Y. Clinical features and genetic analysis of two Chinese families with X-linked ichthyosis. J Int Med Res. 2020 Oct. 48 (10):300060520962292. [QxMD MEDLINE Link].
Das A, Mishra V, Shome K, Sen A. X-linked Ichthyosis Presenting as Erythroderma: A Rare Case. Indian J Dermatol. 2015 Sep-Oct. 60 (5):491-3. [QxMD MEDLINE Link].
Kempster RC, Hirst LW, de la Cruz Z, Green WR. Clinicopathologic study of the cornea in X-linked ichthyosis. Arch Ophthalmol. 1997 Mar. 115(3):409-15. [QxMD MEDLINE Link].
Domínguez-Serrano FB, Caro-Magdaleno M, Mataix-Albert B, Molina-Solana P, Montero-Iruzubieta J, Rodríguez-de-la-Rúa E. Ocular surface analysis in patients diagnosed with X-linked ichthyosis. Arch Soc Esp Oftalmol. 2020 Nov. 95 (11):565-568. [QxMD MEDLINE Link].
Haritoglou C, Ugele B, Kenyon KR, Kampik A. Corneal manifestations of X-linked ichthyosis in two brothers. Cornea. 2000 Nov. 19(6):861-3. [QxMD MEDLINE Link].
Cavenagh A, Chatterjee S, Davies W. Behavioural and psychiatric phenotypes in female carriers of genetic mutations associated with X-linked ichthyosis. PLoS One. 2019. 14 (2):e0212330. [QxMD MEDLINE Link].
Brookes KJ, Hawi Z, Kirley A, Barry E, Gill M, Kent L. Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5. 147B(8):1531-5. [QxMD MEDLINE Link].
Schlotawa L, Steinfeld R, von Figura K, Dierks T, Gartner J. Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency. Hum Mutat. 2008 Jan. 29(1):205. [QxMD MEDLINE Link].
Artigalas OA, da Silva LR, Burin M, Pastores GM, et al. Multiple sulfatase deficiency: clinical report and description of two novel mutations in a Brazilian patient. Metab Brain Dis. 2009 Sep. 24(3):493-500. [QxMD MEDLINE Link].
Aviram-Goldring A, Goldman B, Netanelov-Shapira I, et al. Deletion patterns of the STS gene and flanking sequences in Israeli X-linked ichthyosis patients and carriers: analysis by polymerase chain reaction and fluorescence in situ hybridization techniques. Int J Dermatol. 2000 Mar. 39(3):182-7. [QxMD MEDLINE Link].
Zhu HY, Li HB, Wu LQ, et al. [Multiplex quantitative PCR detection for female carrier in an X-linked ichthyosis family]. Zhonghua Yi Xue Za Zhi. 2008 Dec 16. 88(46):3246-9. [QxMD MEDLINE Link].
Santolaya-Forgas J, Cohen L, Vengalil S, et al. Prenatal diagnosis of X-linked ichthyosis using molecular cytogenetics. Fetal Diagn Ther. 1997 Jan-Feb. 12(1):36-9. [QxMD MEDLINE Link].
Hung C, Ayabe RI, Wang C, Frausto RF, Aldave AJ. Pre-Descemet Corneal Dystrophy and X-Linked Ichthyosis Associated With Deletion of Xp22.31 Containing the STS Gene. Cornea. 2013 Sep. 32(9):1283-7. [QxMD MEDLINE Link]. [Full Text].
Baleviciene G, Schwartz RA. Epidermolytic hyperkeratosis with ichthyosis hystrix. Cutis. 2000 Nov. 66(5):319-22. [QxMD MEDLINE Link].
Paller AS, Browning J, Parish LC, et al. Safety, tolerability, and efficacy of a novel topical isotretinoin formulation for the treatment of X-linked or lamellar congenital ichthyosis: Results from a phase 2a proof-of-concept study. J Am Acad Dermatol. 2022 Mar 7. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Man with preauricular brownish scaling typical of X-linked ichthyosis.
Dirty scale in X-linked ichthyosis.

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Author

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Joshua A Zeichner, MD Assistant Professor, Director of Cosmetic and Clinical Research, Mount Sinai School of Medicine; Chief of Dermatology, Institute for Family Health at North General

Joshua A Zeichner, MD is a member of the following medical societies: American Academy of Dermatology, National Psoriasis Foundation

Disclosure: Received consulting fee from Valeant for consulting; Received grant/research funds from Medicis for other; Received consulting fee from Galderma for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Pharmaderm for consulting; Received consulting fee from Onset for consulting.

X-Linked Ichthyosis Clinical Presentation

History

Physical Examination

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