Mr. and Mrs. Annadurai have a 2 month old baby suffering with Down’s syndrome. Karyotype of Mrs Annadurai shows translocation variety of Down syndrome. Which of the following investigations will you advise to the parents before the next pregnancy ?

**Core Concept**
Down syndrome is a genetic disorder caused by an extra copy of chromosome 21, which occurs in 95% of cases due to nondisjunction during meiosis. In 3-4% of cases, it is caused by a translocation, where a part of chromosome 21 breaks off and attaches to another chromosome, usually chromosome 14, 21, or 22.

**Why the Correct Answer is Right**
In the case of translocation variety of Down syndrome, the parents are at a higher risk of having another child with Down syndrome. To assess the risk, karyotyping of both parents is essential. Specifically, a **Chromosome Analysis** or **Karyotyping** of the mother and father will help identify the translocation and determine the risk of recurrence in subsequent pregnancies. This is crucial for genetic counseling and family planning.

**Why Each Wrong Option is Incorrect**
**Option A:** **AFP (Alpha-Fetoprotein) levels** are used in prenatal screening to detect neural tube defects and Down syndrome, but they do not provide information on the genetic cause of Down syndrome.
**Option B:** **Ultrasound** is a diagnostic tool for fetal development, but it does not assess the genetic risk of Down syndrome.
**Option C:** **Non-invasive prenatal testing (NIPT)** is a screening test for Down syndrome, but it is not diagnostic and does not provide information on the genetic cause of Down syndrome.

**Clinical Pearl / High-Yield Fact**
In cases of translocation Down syndrome, the risk of recurrence is 10-20% if only one parent is a carrier, and 50% if both parents are carriers.

**Correct Answer:** C. Karyotyping of both parents.

✓ Correct Answer: C. Karyotyping