Advanced Paternal Age

Question 1

The mutation rate is higher in men than women, and increases with paternal age because _________________________________

Answer 1

Because of the large number of cell divisions during spermatogenesis

Question 2

The conditions most strongly associated with advanced paternal age are those caused by mutations in the form of single base substitutions (autosomal dominant) and include what? (7 conditions)

Answer 2

• Achondroplasia
• Pfeiffer Syndrome: Premature fusion of certain skull bones (craniosynostosis). Also affects bones in the hands and feet. More than half of all children with Pfieffer syndrome have hearing loss; dental problems are also common. (Genes: FGFR1 or FGFR2)
• Crouzon Syndrome: Premature fusion of certain skull bones (craniosynostosis), may have dental problems, hearing loss, occasionally cleft lip/palate. Usually of normal intelligence. Vision problems caused by shallow eye sockets, strabismus (Gene: FGFR2).
• Apert Syndrome: Form of acrocephalosyndactyly, characterized by malformations of skull, face, hands and feet. (Gene: FGFR2 causes ~2/3 of cases, other third not known)
• Thanatophoric Dysplasia: skeletal disorder characterized by extremely short limbs and folds of extra skin on arms and legs. Narrow chest, short ribs, underdeveloped lungs, and enlarged head with large forehead with prominent wide-spaced eyes. (Gene: FGFR3)
• MEN2A
• MEN2B

Question 3

Advanced Paternal Age is associated with an increased risk for complex disorders such as: (4 answers)

For most conditions, the relative risk is two or less though

Answer 3

• Some congenital anomalies (specifically VSD, ASD, Tracheoesophageal fistula)
• Schizophrenia
• Autism Spectrum disorders
• Some forms of cancer (childhood leukemia, childhood CNS tumor, breast cancer, prostate cancer)

Question 4

Are there currently screening or diagnostic test panels to specifically target conditions increasing with paternal age?

Answer 4

No

Question 5

Recommendations for prenatal counseling session for father of babe with advanced paternal age

Answer 5

The pregnancy should be treated as any other but include a discussion about a potentially increased risk of Down Syndrome attributable to increased paternal age. An ultrasound is recommended at 18-20 weeks to evaluate fetal growth and development (however, it is unlikely to detect many of the conditions of interest).

Question 6

Advanced paternal age defined as _________

Answer 6

40 and older