Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (455 page)

   Deletion/duplication or rearrangements analysis—recommended in patients in which sequencing did not identified any mutation.

   Both sequence analysis and deletion analysis may be required to detect complex BRCA1 or BRCA2 alleles.

   Next-generation sequencing (NGS) testing for hereditary breast and ovarian cancer syndrome is being developed for routine diagnostics to improve genetic testing for BRCA1 and BRCA2 diagnosis due to its huge sequencing capacity and cost-effectiveness.

   Other Considerations

Options for lowering the risk of breast cancer for women at high risk:

   Taking a risk-lowering drug (tamoxifen or raloxifene)

   Having a prophylactic mastectomy

   Having a prophylactic oophorectomy

Suggested Readings

National Cancer Institute Fact Sheet. Available from:
http://www.cancer.gov/cancertopics/ factsheet/Risk/BRCA

Susan G. 2013. Komen® at
http://ww5.komen.org/understandingbreastcancerguide.html

   
DUPLICATION/DELETION SYNDROMES

KLINEFELTER SYNDROME

Males with the 47,XXY karyotype have a fairly well-defined phenotype known as Klinefelter syndrome. They are tall and thin with long legs. Physical appearance is fairly normal until puberty, during which a characteristic eunuchoid habitus develops. Secondary sexual characteristics are underdeveloped, and testes remain small, with azoospermia and subsequent infertility. Gynecomastia can be a feature of this syndrome. IQ is reduced in this population of patients, and two thirds of patients have educational problems, particularly dyslexia.

TRISOMY 13 (PATAU SYNDROME)

   Definition

Trisomy 13 is the third most common viable autosomal trisomy. It has a clinically severe phenotype with severe mental retardation and CNS malformations, often including holoprosencephaly and arhinencephaly. Most trisomy 13 conceptions abort spontaneously; about half of trisomy 13 liveborns die in the 1st month of life. Trisomy 13 is usually caused by meiotic nondisjunction resulting in a karyotype of 47,XX (or XY), +13 with minimal recurrence risk. Risk, as for other autosomal trisomies, increases with advancing maternal age. Other causes may include the presence of a robertsonian translocation in combination with two free copies of chromosome 13; in such cases, one of the parents often is a balanced carrier of the robertsonian translocation. Recurrence risk is low, but significant, and depends on the specific robertsonian translocation and sex of the carrier parent. Prenatal diagnosis (chromosome analysis) should be offered to all Robertsonian translocation carriers.

   Relevant Tests and Diagnostic Value

   Prenatal screening: Maternal serum screening is not applicable for detection of trisomy 13. Fetal abnormalities are significant, however, and are almost always detected with a second-/third-trimester ultrasound scan.