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GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone: 301-519-2100
Fax: 301-519-2892
E-mail: [email protected]
www.genedx.com
Test Information Sheet
Keratin Gene Analysis in Pachyonychia Congenita and
Steatocystoma multiplex
Also known as: Jadassohn-Lewandowsky Syndrome; Jackson-Lawler Syndrome
Related disorders: Steatocystoma multiplex
Mendelian Inheritance in Man Number: Jadassohn-Lewandowsky Syndrome (PC type 1): 167200; JacksonLawler Syndrome (PC type 2): 167210; Steatocystoma multiplex: 184500; KRT6A: 148041; KRT6B:
148042; KRT16: 148067; KRT17: 148069; KRT6C: 612315.
Clinical features:
Pachyonychia congenita (PC) is characterized by thickened and friable finger and toe nails often apparent at
birth or soon after. There are painful plaques of callus-like hyperkeratosis (keratoderma) on palms and soles
with underlying blisters, hyperhidrosis and some individuals may have spiny follicular hyperkeratosis
elsewhere on the body. Patients who also have natal teeth, alopecia and epidermoid cysts were previously
described as having PC type 2. Patients with oral leukoplakia (a finding absent in PC type 2) were previously
described as having PC type 1. However, recent genotype/phenotype correlation reports favor the more
general nomenclature of pachyonychia congenita (PC) due to high phenotypic overlap between the subtypes.
Heterozygous mutations in five keratin genes have been associated with PC: KRT16, KRT6A, KRT17,
KRT6B, and KRT6C. Patients with KRT6C mutations typically have callus-like palmoplantar keratoderma
with little or no nail dystrophy.
In steatocystoma multiplex, multiple round or oval sebaceous (epidermoid) cysts develop, widely distributed
over the back, anterior trunk, arms, scrotum, and thighs. Thickened nail plates, focal palmoplantar
keratoderma and natal teeth are variable features.
Inheritance pattern: Autosomal dominant
Reasons for referral:
1. Confirmation of clinical diagnosis
2. Differentiation from other ectodermal dysplasias
3. Prenatal diagnosis
Test method:
Using genomic DNA obtained from submitted biological material, bi-directional sequence analysis of select
exons (hotspot regions) is performed in the KRT16, KRT6A, KRT17, KRT6B, and KRT6C genes. In
steatocystoma multiplex, select exons in only KRT17 are screened. If no mutation is identified by hotspot
analysis, sequence analysis of the entire coding region of the gene(s) is available. If a mutation is identified,
the result will be confirmed by repeat analysis using sequencing, restriction fragment analysis, or another
appropriate method.
Information Sheet on Pachyonychia Congenita
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© GeneDx Revision Date: 5/12
Test sensitivity:
Analysis of the mutational hotspots in the KRT16, 6A, 17, 6B, and 6C genes (specifically the sequence
regions coding for the ends of the rod domains of the respective keratin proteins) is expected to identify the
vast majority of mutations in pachyonychia congenita (PC). Some patients with the clinical diagnosis of PC
have been found to have a mutation in the GJB6 gene (usually associated with Clouston syndrome). Analysis
of the GJB6 gene should be considered in those patients with PC in whom no keratin gene mutation has been
identified; testing is available as a separate test (see information material for GJB6 testing in ‘Clouston
syndrome’).
Mutation spectrum:
Most mutations in keratin genes associated with PC are missense mutations or small in-frame deletions that
affect the ends of the rod domains of the keratin proteins and affect stability of keratin intermediate filaments.
Specimen Requirements and Shipping/Handling:
• Blood: A single tube with 1-5 mL whole blood in EDTA. Ship overnight at ambient temperature, using a
cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.
• Buccal Brushes: As an alternative to blood, use a GeneDx buccal kit (others not accepted). Submit by
mail. Buccal brushes are not accepted on children less than 6 months of age.
• Prenatal Diagnosis: For prenatal testing for a known mutation in one of the genes above please refer to
the specimen requirements table on our website at: http://www.genedx.com/test-catalog/prenatal/
Required Form:
• Sample Submission (Requisition) Form – complete all pages, including payment options page
References Cited: Terrinoni et al. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and
K17 in 13 cases of pachyonychia congenita. J Invest Dermatol 117:1391-1396, 2001; Van Steensel et al. Clouston
syndrome can mimic pachyonychia congenita. J Invest Dermatol 121:1035-1038, 2003. Smith et al. Missense
mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma
multipolex. J Invest Dermatol 1108:220-223, 1997; Eliason et al. A review of the clinical phenotype of 254
patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol epub Jan 2012. Akasaka et al.
Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation. Br J Dermatol. 165:12901292, 2011. Wilson et al. Keratin K6c Mutations Cause Focal Palmoplantar Keratoderma. J Invest Dermatol
130:425-429, 2010.
Information Sheet on Pachyonychia Congenita
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© GeneDx Revision Date: 5/12