Information for clinicians
8 Genetic counselling
8a Mode of inheritance
Adult Refsum's disease is inherited in an autosomal recessive manner.
8b Risk to family members
8b(i) Parents of a proband
- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.
- Their recurrence risk for future children is 50%.
- Heterozygotes (carriers) are asymptomatic.
8b(ii) Sibs of a proband
- At conception, the sibs of an affected individual have a 25% chance of being affected, a 50% chance of being asymptomatic carriers, and a 25% chance of being unaffected and not carriers.
- Once an at-risk sib is known to be unaffected, the risk of his/her being carrier is 2/3.
8b(iii) Offspring of a proband
- The offspring of an individual with adult Refsum's disease are obligate heterozygotes (carriers) for a disease-causing mutation.
8b(iv) Other family members of a proband
- Sibs of the proband's parents are at 50% risk of being carriers.
8c Carrier detection
Carrier testing using molecular genetic techniques may be available on a clinical basis once the mutations have been identified in the proband.
Biochemical testing is not accurate for carrier testing, as the biochemical markers in obligate heterozygotes (carriers) are normal.
8d Related genetic counselling issues
8d(i) Family planning
The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
8d(ii) DNA banking
DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%.
8e Prenatal testing
8e(i) Molecular genetic testing
Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation* or chorionic villus sampling (CVS) at about 10-12 weeks' gestation. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.
8e(ii) Biochemical genetic testing
In principle, prenatal diagnosis for pregnancies at 25% risk is possible by measurement of phytanic acid oxidation in fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation* or chorionic villus sampling (CVS) at about 10-12 weeks' gestation.
Requests for prenatal testing for conditions such as adult Refsum's disease, which is usually diagnosed when individuals are in their twenties and their parents have typically completed their families, are uncommon occurrences.
*Gestational age is expressed as menstrual
weeks calculated either from the first day of the last normal menstrual period
or by ultrasound measurements.
Next: Molecular genetics
Page last updated 26 June 2006