A newborn boy has multiple congenital anomalies and the mother has a history of recurrent miscarriages. What is the most likely genetic mechanism?

A newborn boy has multiple congenital anomalies and the mother has a history of recurrent miscarriages. What is the most likely genetic mechanism?

• A. Balanced translocation
• B. Unbalanced chromosomal rearrangement
• C. Nondisjunction
• D. De Novo mutation

Answer: (B)

The scenario points to a parent who carries a balanced chromosomal rearrangement. When someone has a balanced translocation, all genetic material is present and the person is typically phenotypically normal. However, during meiosis, the rearranged chromosomes can segregate so that the resulting gametes contain extra or missing chromosome segments. If such a gamete is fertilized, the fetus ends up with unbalanced chromosomal content, leading to multiple congenital anomalies and often miscarriage. This explains both the affected newborn and the mother’s history of recurrent pregnancy loss. Nondisjunction would create random whole-chromosome aneuploidies, which can cause syndromes like Down syndrome but don’t typically account for a pattern of recurrent miscarriages with an affected child due to a parental rearrangement. A de novo mutation affects the child anew and wouldn’t explain a maternal history of repeated losses.

The scenario points to a parent who carries a balanced chromosomal rearrangement. When someone has a balanced translocation, all genetic material is present and the person is typically phenotypically normal. However, during meiosis, the rearranged chromosomes can segregate so that the resulting gametes contain extra or missing chromosome segments. If such a gamete is fertilized, the fetus ends up with unbalanced chromosomal content, leading to multiple congenital anomalies and often miscarriage. This explains both the affected newborn and the mother’s history of recurrent pregnancy loss.

Nondisjunction would create random whole-chromosome aneuploidies, which can cause syndromes like Down syndrome but don’t typically account for a pattern of recurrent miscarriages with an affected child due to a parental rearrangement. A de novo mutation affects the child anew and wouldn’t explain a maternal history of repeated losses.