Which chromosome is involved in myotonic dystrophy?

Explanation

## Correct Answer: A. Chromosome 19 Myotonic dystrophy (MD) is caused by a trinucleotide repeat expansion (CTG repeats) in the DMPK gene located on **chromosome 19q13.3**. This is the most common form of muscular dystrophy in adults in India and worldwide. The pathophysiology involves expansion of CTG repeats (normal: 5–37 repeats; affected: >50 repeats) leading to toxic gain-of-function through sequestration of RNA-binding proteins (MBNL1 and CUG-BP1), which disrupts splicing of multiple genes including the chloride channel (CLCN1) and insulin receptor. This results in the characteristic clinical triad: myotonia (delayed muscle relaxation), progressive muscle weakness, and multisystem involvement (cardiac arrhythmias, cataracts, hypogonadism, cognitive decline). The repeat number shows **anticipation**—particularly paternal transmission shows dramatic expansion in successive generations. Diagnosis is confirmed by genetic testing showing CTG repeat expansion on chromosome 19. Understanding the chromosomal location is essential for genetic counseling and prenatal diagnosis in Indian families with MD. ## Why the other options are wrong **B. Chromosome 21** — Chromosome 21 is associated with Down syndrome (trisomy 21) and carries genes like APP (Alzheimer disease), not the DMPK gene. This is a common distractor because chromosome 21 is frequently tested in genetics; students may confuse it with other genetic disorders. MD is autosomal dominant, not a chromosomal aneuploidy. **C. Chromosome 20** — Chromosome 20 is not involved in myotonic dystrophy. This option may trap students who guess nearby chromosome numbers without recalling the specific locus. MD type 2 (a rarer form) involves chromosome 3, but the classic and most common form (MD1) is on chromosome 19. **D. Chromosome 22** — Chromosome 22 carries genes for DiGeorge syndrome (22q11 deletion) and neurofibromatosis type 2 (NF2), not DMPK. This is a distractor for students who confuse autosomal genetic disorders. The correct locus for myotonic dystrophy is 19q13.3, not 22q. ## High-Yield Facts - **Chromosome 19q13.3** harbors the DMPK gene; CTG repeat expansion (>50 repeats) causes myotonic dystrophy type 1 (MD1). - **Anticipation** is a hallmark of MD: repeat number expands in successive generations, especially with paternal transmission, causing earlier onset and severity. - **Myotonia** (delayed muscle relaxation after contraction) is the pathognomonic feature; caused by chloride channel dysfunction due to abnormal RNA splicing. - **Multisystem involvement** in MD includes cardiac (arrhythmias, conduction defects), ocular (cataracts, ptosis), endocrine (hypogonadism, insulin resistance), and CNS manifestations. - **Congenital myotonic dystrophy** occurs when mother is affected; presents with severe hypotonia, respiratory distress, and developmental delay in neonates. ## Mnemonics **MD Chromosome Memory** **19** = **M**yotonic **D**ystrophy (19 sounds like 'nineteen'—remember 'MD on 19'). Chromosome 19 = DMPK gene = CTG repeats. **Anticipation in MD** **PAT**ernal **ANT**icipation = Paternal transmission shows dramatic expansion; maternal transmission shows milder expansion. Congenital form occurs only with maternal transmission. ## NBE Trap NBE may pair chromosome 21 (Down syndrome) with genetic disorders to trap students who confuse aneuploidy syndromes with single-gene repeat expansion disorders. The key discriminator is that MD is autosomal dominant with trinucleotide repeat expansion, not a chromosomal aneuploidy. ## Clinical Pearl In Indian clinical practice, myotonic dystrophy often presents in adults with "stiff hand" complaints and cataracts; the diagnosis is often delayed because myotonia is mistaken for rigidity. Genetic testing for CTG repeats on chromosome 19 is now available in major Indian tertiary centers and is essential for family screening and prenatal counseling in affected families. _Reference: Robbins & Cotran Pathologic Basis of Disease, Ch. 5 (Genetic Disorders); Harrison's Principles of Internal Medicine, Ch. 452 (Muscle Diseases)_