Steriod Sulphatase Deficiency

Ichthyosis is a genetically heterogeneous disorder of the skin. Onset of the X-linked form of ichthyosis is generally at birth or within the first year of life. Scaling of the skin may occur over the scalp, ears, neck, trunk, extremities and some flexures. Most individuals demonstrate only dermatologic features. In a minority of cases, however, the ichthyosis occurs as part of a contiguous gene deletion disorder that can include developmental delay/mental retardation, Kallmann syndrome, ocular albinism, and/or chondrodysplasia punctata. It is not uncommon for male fetuses with X-linked ichthyosis to be detected prenatally as an incidental finding during maternal serum screening due to significantly decreased serum unconjugated estriol (uE3).

Approximately 85% of males with isolated X-linked ichthyosis have the condition due to a 1 – 2 Mb deletion that encompasses the STS gene; most of the remaining isolated cases harbor STS point mutations. Contiguous gene deletions of varying sizes involving surrounding genes have been described in approximately 8% of X-linked ichthyosis and invariably present with additional phenotypic features beyond that of ichthyosis.

1. Confirmation of diagnosis:
   1. Males suspected to have X-linked ichthyosis
2. Carrier testing: 
   1. This testing can only be ordered by Medical Geneticists after the patient has had genetic counselling. Pregnant women carrying a male fetus and presenting with significantly reduced unconjugated estriol (uE3) on maternal serum screening ONLY IF the decision regarding whether or not to pursue amniocentesis will be impacted by the results of the testing.

      NB: Carrier testing for any other indication should be performed by the Vancouver Hospital Cytogenetics Lab using fluorescent in situ hybridization (FISH).
       

3. Prenatal testing (prenatal diagnosis requests are not normally accepted from physicians other than Medical Geneticists):
   1. Pregnancies at risk of X-linked ichthyosis due to a significantly reduced unconjugated estriol (uE3) and where the fetus has been found to be male by ultrasound.
   2. Pregnancies of known STS deletion carriers. Prior to testing for STS, fetal sexing is performed; if the fetus is female, further testing is not indicated.

In males, multiplex PCR analysis is used to assess for the presence of deletion of the STS gene; if a deletion is identified, additional PCR testing is performed to estimate the extent of the deletion.

Carrier testing in females is typically performed by the Vancouver Hospital Cytogenetics laboratory using fluorescent in situ hybridization (FISH). In females where molecular analysis is indicated, multiplex ligation-dependent probe amplification (MLPA) analysis is carried out with the P160-A2 probe mix (MRC-Holland) to detect each of the 10 exons of STS, as well as the NLGN4X, HDHD1A, KAL1, and OA1 genes.

Pregnancy-related/Prenatal

If pregnancy management will be altered, 3 weeks; otherwise, routine TAT.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays).  

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used. This method will not detect all mutations (e.g., point mutations in the coding region, promoter mutations, and regulatory element mutations). In rare cases, a point mutation could be detected.

For carrier/predictive testing due to family history, it is generally important to first document the gene mutation in an affected or carrier family member. This information should be provided to the laboratory for assessment of whether the assay is appropriate for detection of the familial mutation, and to aid in the interpretation of data.

In some cases, DNA alterations of undetermined or unclear clinical significance may be identified.

Rare single nucleotide variants or polymorphisms could lead to false-negative results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.