Two individuals are considered consanguineous if they have at least one recent ancestor in common. Although uncommon in Western countries, more than 1 billion people are estimated to live in countries in which 20 to 50 percent of marriages are consanguineous (Romeo, 2014). In medical genetics, a union is consanguineous if between second cousins or closer relatives. First-degree relatives share half of their genes, second-degree relatives share a fourth, and third-degree relatives-first cousins-share one eighth. Because of the potential for shared deleterious genes, consanguinity confers an increased risk to have ofspring with otherwise rare autosomal recessive diseases or multifactorial disorders. In population-based series, first cousins are reported to have a twofold risk for congenital anomalies (Sheridan, 2013; Stoltenberg, 1997). Consang�inity also is associated with a greater rate of stillbirth (Kapurubandara, 2016). Because CMA performed using a single-nucleotide polymorphism platform may identiy consanguinity, it is important that preprocedural counseling include this possibility.
Incest is defined as a sexual relationship between first-degree relatives such as parent-child or brother-sister and is universally illegal. Progeny of such unions carry the highest risk of abnormal outcomes, and older studies reported that up to 40 percent of ofspring were abnormal as a result of recessive and multifactorial disorders (Baird, 1982; Freire-Maia, 1984).
Most X-linked diseases are recessive. Common examples include color blindness, hemophilia A and B, and Duchenne and Becker muscular dystrophy. Males with an X-linked recessive gene are usually afected by the disease it causes, because they lack a second X chromosome to express the normal dominant gene. A male with an X-linked disease cannot have afected sons because they cannot receive his X chromosome. When a woman carries a gene causing an X-linked recessive condition, each of her sons has a 50-percent risk of being afected, and each daughter has a 50-percent chance of being a carrier.
Women with an X-linked recessive gene are generally unaffected by the disease it causes. In some cases, however, the random inactivation of one X chromosome in each cell-termed lyonization-is skewed, and female carriers may have features of the condition. For example, approximately 10 percent of female carriers of hemophilia A will have factor VIII levels less than 30 percent of normal, and a similar proportion of female hemophilia B carriers have factor IX levels less than 30 percent. Levels below these thresholds confer a greater risk for abnormal bleeding when afected women give birth (Plug, 2006). Indeed, even with higher levels, carriers are reported to be at increased risk for bleeding complications (Olsson, 2014). Similarly, female carriers of Duchenne or Becker muscular dystrophy carry an elevated risk for cardiomyopathy, and periodic evaluation for cardiac dysfunction and neuromuscular disorders is recommended (American Academy of Pediatrics, 2008).
X-linked dominant disorders mainly afect females, because they tend to be lethal in males. Two examples are vitamin D-resistant rickets and incontinentia pigmenti. One exception is fragile X syndrome, which is discussed subsequently.
he prevalence of Y-linked chromosomal disorders is low.
This chromosome carries genes important for sex determination and various cellular functions related to spermatogenesis and bone development. Deletion of genes on the long arm of Y results in severe spermatogenic defects, whereas genes at the tip of the short arm are critical for chromosomal pairing during meiosis and for fertility.