Which of the following is autosomal dominant?

Explanation

## Correct Answer: C. Achondroplasia Achondroplasia is the most common form of inherited dwarfism in humans and follows **autosomal dominant inheritance**. A single mutated allele on chromosome 4 (FGFR3 gene) is sufficient to cause the phenotype, meaning heterozygous individuals (Aa) manifest the disease while homozygous dominant (AA) is typically lethal in utero. The mutation results in abnormal endochondral ossification, leading to short stature with characteristic features: short limbs (rhizomelic shortening), normal trunk, frontal bossing, and midface hypoplasia. Approximately 80% of cases arise from de novo mutations, particularly in paternal gametes, explaining why advanced paternal age is a risk factor. In India, achondroplasia is seen across all populations and represents a significant proportion of dwarfism cases. Affected individuals have normal intelligence and can reproduce; if both parents are heterozygous, there is a 25% risk of homozygous offspring (usually lethal). The diagnosis is clinical and confirmed by genetic testing or imaging showing characteristic skeletal changes. ## Why the other options are wrong **A. Sickle cell anaemia** — Sickle cell anaemia is **autosomal recessive**, requiring two mutated alleles (HbS/HbS) for the full disease phenotype. Heterozygotes (HbA/HbS) show sickle cell trait with minimal symptoms. This is a common trap because both achondroplasia and sickle cell are monogenic disorders, but their inheritance patterns differ fundamentally. In India, sickle cell is prevalent in tribal populations of central India (Madhya Pradesh, Chhattisgarh). **B. Duchenne muscular dystrophy** — Duchenne muscular dystrophy (DMD) is **X-linked recessive**, caused by mutations in the dystrophin gene on the X chromosome. Males (XY) with one mutated allele are severely affected, while females (XX) are usually carriers. This is a classic NBE trap: both achondroplasia and DMD are severe genetic disorders presenting in childhood, but DMD's X-linked pattern makes it fundamentally different from autosomal dominant inheritance. **D. Cystic fibrosis** — Cystic fibrosis is **autosomal recessive**, caused by mutations in the CFTR gene on chromosome 7. Homozygous or compound heterozygous individuals develop the disease; heterozygotes are asymptomatic carriers. While both achondroplasia and CF are autosomal, CF requires two mutated alleles, making it recessive. In India, CF is less common than in Caucasian populations but is increasingly recognized in urban centers. ## High-Yield Facts - **Achondroplasia** is autosomal dominant; heterozygotes (Aa) are affected, homozygotes (AA) are usually lethal in utero. - **FGFR3 gene mutation** on chromosome 4 causes achondroplasia; ~80% are de novo mutations with paternal age effect. - **Rhizomelic shortening** (short limbs with normal trunk) is the hallmark skeletal feature of achondroplasia. - **Sickle cell** (autosomal recessive), **DMD** (X-linked recessive), and **CF** (autosomal recessive) are all recessive disorders. - **Advanced paternal age** increases risk of achondroplasia due to increased de novo mutations in spermatogenesis. ## Mnemonics **Autosomal Dominant Dwarfism = ACHONDROPLASIA** When you see 'dwarfism + dominant inheritance' → think ACHONDROPLASIA. The 'A' at the start reminds you it's Autosomal. Heterozygotes survive and show disease; homozygotes die in utero. **Recessive Traps in Genetics MCQs** SCD (Sickle Cell Disease) = Autosomal Recessive; DMD (Duchenne) = X-linked Recessive; CF (Cystic Fibrosis) = Autosomal Recessive. Only ACHONDROPLASIA is Dominant. ## NBE Trap NBE pairs achondroplasia with other monogenic disorders (SCD, DMD, CF) to test whether students confuse "single-gene disorder" with "dominant inheritance." The trap is that all four are monogenic, but only achondroplasia is dominant.</trap> <parameter name="textbookRef">Robbins Ch. 5 (Genetic Disorders); Harrison Ch. 417 (Genetic Counseling & Inheritance Patterns); KD Tripathi Ch. 2 (Genetics) ## Clinical Pearl In Indian clinical practice, achondroplasia is the most common cause of disproportionate dwarfism seen in outpatient clinics. Unlike recessive disorders (SCD, CF) that require carrier screening in families, achondroplasia often presents as a sporadic case with no family history due to de novo mutations—a key counseling point for Indian parents who may initially fear genetic burden in subsequent pregnancies.</clinicalPearl> </invoke>