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During the last decade, our understanding of the molecular bases
for genetic disorders of the skin has expanded tremendously. Identifying
the gene mutations that lead to phenotypic manifestations facilitates
prenatal diagnosis using molecular techniques. For some disorders,
this information has translated into early trials of gene therapy
or the development of new pharmacologic therapy based on manipulation
of gene product levels. Several support groups that provide education
for patients and physicians are available and are listed for each
subgroup of genetic disorders of skin. The National Organization
for Rare Disorders (NORD) at http://www.rarediseases.org can
also help families for whom there is no specific support group. More
information about specific genetic disorders can be found at http://www.ncbi.nih.gov/sites/entrez?db=OMIM and
about the availability of genetic testing at http://www.genetests.org.
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Named for the Greek term meaning “fishlike scales,” this
heterogeneous group of disorders is characterized by the predominant
clinical feature of visible accumulation of scale. FIRST (Foundation
for Ichthyosis and Related Skin Types) is a national support group
for patients with the ichthyoses and other disorders with thickening
of epidermis (http://www.scalyskin.org).
During the past decade, the underlying molecular basis for many of
the ichthyotic disorders has been discovered, and many can be diagnosed
prenatally through molecular analysis of genomic DNA obtained by
chorionic villus sampling or amniocentesis. If possible, specific
diagnosis should be made as early as possible to aid in prognostication
and genetic counseling. In general, therapy for these disorders
is similar and is based on disease severity and tolerance rather
than the specific type. During the neonatal and early infantile
period, however, therapy should be limited to the frequent application
of bland emollients, since use of topical medications with keratolytic
agents during the first 6 months of life is usually unnecessary
and risks significant absorption of potentially toxic substances
(eg, absorption of lactic acid, salicylic acid).
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Scaling in the genetic forms is usually either present at birth
or has its onset within the first few years of life. Rarely, nongenetic
causes lead to ichthyosis in pediatric patients. Causes of acquired
ichthyosis include hypothyroidism, chronic renal insufficiency,
malignancy (particularly lymphoma), malabsorption syndromes, essential fatty
acid deficiency, sarcoidosis, and certain drugs (particularly hypocholesterolemic
agents).
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Ichthyosis vulgaris is the most common form
of the ichthyoses.1,2 It is now known to result from mutations
in the gene encoding filaggrin, a gene also recently implicated
in atopic dermatitis. Approximately 1 in 20 Northern European individuals
carry a mutation on 1 allele and have a mild form; homozygotes have
a much more severe form. Thus, the disorder is not autosomal dominant,
as was once thought, but is semidominant. Regardless of severity,
the onset of scaling in ichthyosis vulgaris tends to be after 3
months of age and may become more prominent later during childhood
or at puberty. Fine, white scales, often without much erythema,
predominate on the exterior surfaces of the extremities, especially
the legs (Fig. 360-1). There
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