A 33-year-old woman, gravida 2 para 1, comes to the office for a prenatal visit at 20 weeks gestation. She feels well and reports experiencing fetal movements. The patient has no medical problems other than a history of cleft lip, which was repaired in childhood. Her husband is healthy, but her previous child was born with spina bifida. She takes a daily prenatal vitamin. Physical examination is unremarkable and uterine size is in accordance with ultrasound dates. The patient is worried that the fetus may develop the same birth defect as her previous child. Which of the following is the most likely mode of inheritance of this disorder?

Question

A 33-year-old woman, gravida 2 para 1, comes to the office for a prenatal visit at 20 weeks gestation.  She feels well and reports experiencing fetal movements.  The patient has no medical problems other than a history of cleft lip, which was repaired in childhood.  Her husband is healthy, but her previous child was born with spina bifida.  She takes a daily prenatal vitamin.  Physical examination is unremarkable and uterine size is in accordance with ultrasound dates.  The patient is worried that the fetus may develop the same birth defect as her previous child.  Which of the following is the most likely mode of inheritance of this disorder?

Quizplus · Accepted Answer

Multifactorial inheritance is a term used to describe a complex process by which numerous genetic and environmental factors interact to determine phenotypic expression. Unlike single-gene disorders, diseases displaying multifactorial inheritance make precise genetic analysis and counseling extremely challenging due to their intricate development process. What is understood about these diseases is that the closer a relative is to the affected person, the more likely the relative is to develop the trait. Spina bifida is an example of a multifactorial condition. There are a multitude of different genes that play a role in neurulation, the process responsible for formation of the neural tube. In addition to genetic factors, a number of environmental factors have profound effects on neural tube development; the most well known is dietary folate deficiency. Neural tube defects are more common in first-degree relatives of those affected, with a recurrence risk of 2%-5%. In general, most multifactorial conditions have a lower recurrence risk than autosomal dominant and autosomal recessive diseases, which convey a 50% and 25% risk to first-degree family members, respectively. Other examples of multifactorial diseases include cleft lip and palate, diabetes mellitus, coronary artery disease, and hypertension. (Choice A) A condition inherited in an autosomal dominant pattern will be expressed in 50% of offspring when 1 parent is affected. Classic examples include Huntington disease, Marfan syndrome, multiple endocrine neoplasias, and the neurofibromatoses. (Choice B) A condition inherited in an autosomal recessive fashion will be expressed in 25% of offspring when both parents are carriers. Cystic fibrosis, hemochromatosis, and sickle cell anemia are examples of autosomal recessive diseases. (Choice C) Humans inherit mitochondrial DNA only from their mothers; therefore, mitochondrial inheritance is purely maternal. Disorders transmitted via mitochondrial inheritance display variable expressivity, meaning that severity of phenotypic expression can differ greatly even among close relatives. Examples of mitochondrial diseases are myoclonic epilepsy and Leber hereditary optic neuropathy. (Choice E) X-linked recessive inheritance refers to a trait that is passed via the X chromosome in a recessive manner. Phenotypic expression in offspring is dependent on the sex of the child; all males who inherit the X chromosome will display the phenotype whereas only homozygous females will display the phenotype. Examples include Duchenne and Becker muscular dystrophy, hemophilia, and G6PD deficiency. Educational objective: Many frequently encountered diseases (eg, hypertension, spinal bifida) display multifactorial inheritance, which involves the complex interaction of numerous genetic and environmental factors to determine phenotypic expression. Although the exact inheritance risk cannot be determined, the closer a relative is to the affected person, the more likely the relative is to develop the trait. __________ References: Mouse as a model for multifactorial inheritance of neural tube defects. (http://www.ncbi.nlm.nih.gov/pubmed/22692891)

A 33-Year-Old Woman, Gravida 2 Para 1, Comes to the Office