الأمراض الجينية Genetic Diseases

Genetic Disease
Case 1
A 4-year-old boy is brought in with pain and swelling of the right thigh after a fall in the home. An x-ray film reveals an acute fracture of the right femur. Questioning of the mother reveals that the boy has had two other known fractures—left humerus and left tibia—both with minimal trauma. The family history is notable for a bone problem during childhood in the boy's father that got better as he grew into adulthood. A diagnosis of osteogenesis imperfecta is entertained.
Questions
A. What are the four types of osteogenesis imperfecta? How are they genetically transmitted?
B. Which two types are most likely in this patient? How might they be distinguished clinically?
C. Further workup results in a diagnosis of type I osteogenesis imperfecta. What clinical features may the boy expect in adult life?
D. What is the pathogenesis of this patient's disease?
Case 2
A young woman is referred for genetic counseling. She has a 3-year-old boy with developmental delay and small joint hyperextensibility. The pediatrician has diagnosed fragile X-associated mental retardation. She is currently pregnant with her second child at 14 weeks of gestation. The family history is unremarkable.
Questions
A. What is the genetic mutation responsible for fragile X-associated mental retardation? How does it cause the clinical syndrome of developmental delay, joint hyperextensibility, large testes, and facial abnormalities?
B. Which parent is the probable carrier of the genetic mutation? Explain why this parent and the grandparents are phenotypically unaffected.
C. What is the likelihood that the unborn child will be affected?
Case 3
A 40-year-old woman, recently married and pregnant for the first time, comes to clinic with a question about the chances of having "a Down syndrome baby."
Questions
A. What is the rate of occurrence of Down syndrome in the general population? What are some of the its common clinical features?
B. What major genetic abnormalities are associated with Down syndrome? How might these abnormalities lead to the clinical features of the syndrome?
C. How might this woman's age contribute to her risk of having a child with Down syndrome?
Case 4
A newborn girl of Yemenite Jewish descent presents in pediatric clinic. A screening test for phenylketonuria was suggestive of the disease.
Questions
A. What is the incidence of phenylketonuria in the general population? How does the risk differ among ethnic groups?
B. What is the primary defect in phenylketonuria?
C. What are the clinical manifestations of phenylketonuria? What is the pathophysiology underlying them?
D. How can phenylketonuria be treated?
E. When this child is of childbearing age, what should she be told about the risks to her baby should she become pregnant?
Osteogenesis Imperfecta[left]