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Ichthyosis, X-Linked: Differential Diagnoses & Workup

Author: Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: May 29, 2009

Differential Diagnoses

Asteatotic Eczema
Atopic Dermatitis
Ichthyosis Vulgaris, Hereditary and Acquired
Ichthyosis, Lamellar

Other Problems to Be Considered

Multiple sulfatase deficiency is a rare inborn autosomal recessive disorder that combines the clinical features of metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis (XLI).14

Workup

Laboratory Studies

  • Diagnosis of patients with X-linked ichthyosis and female carriers is based on biochemical and genetic analysis. Genetic analysis currently is the most accurate diagnostic method in most patients.
    • X-linked ichthyosis can be diagnosed by assaying STS activity in the placenta or in the skin fibroblasts, keratinocytes, or lymphocytes of patients after birth.
    • Patients show a deficiency of arylsulfatase C, which can be demonstrated by biochemical testing.
    • Polymerase chain reaction (PCR) and Southern blot testing are useful for the genetic diagnosis of X-linked ichthyosis, although a few patients with X-linked ichthyosis carrying point mutations rather than deletions may be missed. PCR is not applicable for carrier detection.
    • Both multiplex quantitative fluorescent PCR (QF-PCR) and fluorescence in situ hybridization (FISH) are effective to detect the complete deletion mutation of the STS gene and identify the female carrier.15 Multiplex QF-PCR appears to be more convenient and automatic compared with FISH.16
  • X-linked ichthyosis can be diagnosed prenatally using fluorescence in situ hybridization.17
    • Maternal peripheral blood metaphase spreads may display 2 hybridization signals on one of the X chromosomes (1 in the STS region [band Xp22.3] and 1 in the centromeric region), but only 1 hybridization signal (in the X centromeric region) on the other X chromosome; therefore, one of the X chromosomes has a deletion in the band Xp22.3 region, a result consistent with the carrier status for STS deficiency and X-linked ichthyosis.
    • In metaphase spreads from amniotic fluid samples, the X chromosome shows 1 hybridization signal in the control region, but no hybridization signal in the STS region. Therefore, the X chromosome of this male fetus has a deletion in the STS region, a result consistent with X-linked ichthyosis.
  • The deficit in placental STS blocks placental steroid synthesis, resulting in excretion of maternal urinary steroids in much lower amounts than normal.
    • Incorporating unconjugated estriol in maternal serum into the calculation of risk increases the yield of screenings performed during pregnancy for detection of fetal chromosomal and structural anomalies.
    • The differential diagnosis of low and undetectable levels of unconjugated estriol in maternal serum includes X-linked ichthyosis and serious fetal pathologies (eg, adrenal insufficiency, anencephaly, Down syndrome).
    • To diagnose X-linked ichthyosis, examine the urine of these pregnant women for low levels of nonhydrolyzed sulfated steroids.

Histologic Findings

Histologic changes of X-linked ichthyosis often are subtle. Biopsy specimens from ichthyotic skin with mild scaling may appear normal. Specimens obtained from regions of thick scaling (eg, anterior aspect of legs, extensor aspect of arms) show mild-to-moderate compact laminated eosinophilic orthokeratotic hyperkeratosis, with a normal or slightly thickened granular layer 3-4 cells thick, mild acanthosis, well-preserved rete ridges, and a sparse perivascular and periappendageal lymphohistiocytic infiltrate.

Ultrastructurally, keratohyaline granules are increased in size and number. Normal-appearing keratinocytes appear linked by desmosomal disks all the way up into the stratum corneum, where the anucleated cells have increased numbers of melanosomes, which may account for the dark coloration of scaling in X-linked ichthyosis.

More on Ichthyosis, X-Linked

Overview: Ichthyosis, X-Linked
Differential Diagnoses & Workup: Ichthyosis, X-Linked
Treatment & Medication: Ichthyosis, X-Linked
Follow-up: Ichthyosis, X-Linked
Multimedia: Ichthyosis, X-Linked
References
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References

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  13. 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. Dec 5 2008;147B(8):1531-5. [Medline].

  14. 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. Jan 2008;29(1):205. [Medline].

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  34. Zalel Y, Kedar I, Tepper R, et al. Differential diagnosis and management of very low second trimester maternal serum unconjugated estriol levels, with special emphasis on the diagnosis of X-linked ichthyosis. Obstet Gynecol Surv. Mar 1996;51(3):200-3. [Medline].

  35. Zettersten E, Man MQ, Sato J, et al. Recessive x-linked ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality. J Invest Dermatol. Nov 1998;111(5):784-90. [Medline].

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Further Reading

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Keywords

ichthyosis nigricans, X-linked ichthyosis, enzyme deficiency, XLI

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Contributor Information and Disclosures

Author

Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, 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, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Bernice R Krafchik, MBChB, FRCPC, Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto
Bernice R Krafchik, MBChB, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Royal College of Physicians and Surgeons of Canada, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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