---

8-Year-Old: Ptosis + Grip Myotonia — Clinical Analysis

Most Likely Diagnosis: Myotonic Dystrophy Type 1 (DM1 / Steinert's Disease)

---

Pathophysiology

• Gene: DMPK gene on chromosome 19q13
• Mutation: CTG trinucleotide repeat expansion (normal: 5–37 repeats; affected: 50 to several thousand)
• Mechanism: "Toxic RNA gain-of-function" — expanded CUG RNA sequesters RNA-binding proteins (MBNL1), disrupting splicing of multiple genes including chloride channel (CLCN1), causing chloride channelopathy → myotonia
• Inheritance: Autosomal dominant; anticipation occurs (earlier/more severe presentation with each generation due to increasing CTG repeats)

---

Clinical Features in Children (Juvenile/Childhood-Onset DM1)

Neuromuscular

Multisystem Involvement (Childhood DM1)

In childhood-onset DM1, cognitive and fine motor difficulties dominate the clinical picture more than in adults — Robbins & Kumar Basic Pathology; Goldman-Cecil Medicine

---

Key Clinical Signs to Elicit

1. Percussion myotonia — tap thenar eminence/tongue with tendon hammer → sustained contraction
2. Warm-up phenomenon — myotonia decreases with repeated movements (distinguishes from paramyotonia)
3. Handshake myotonia — patient cannot release handshake quickly
4. Eye closure myotonia — after forced eye closure, eyes open slowly
5. Hatchet face — temporalis/masseter wasting, elongated face
6. Ptosis — bilateral, partial; differs from MG (no fatigability)
7. Frontal balding (more pronounced in adults)
8. Percussion dimple on tongue

---

Differential Diagnosis

---

Investigations

First-Line

Second-Line / Systemic Evaluation

---

Management

Myotonia Treatment

• Mexiletine (sodium channel blocker) — first-line for symptomatic myotonia
• Alternatives: phenytoin, carbamazepine, acetazolamide
• Avoid depolarizing agents (succinylcholine) — triggers myotonic crisis
• Avoid cold exposure — worsens myotonia

Multidisciplinary Approach

---

Classic Teaching Points for Exams

• "Warm-up phenomenon" = myotonia that improves with repeated activity → DM1 (contrast: paramyotonia worsens with activity)
• "Dive-bomber" EMG = pathognomonic for myotonia
• Anticipation: each generation gets more severe/earlier onset due to expanding CTG repeats
• Maternal transmission → more likely to produce congenital DM1 (severe form)
• Ptosis in DM1 is due to levator palpebrae myotonia + weakness, not fatigable (unlike MG)
• DM1 is the most common adult-onset muscular dystrophy, but childhood/juvenile onset is well-recognized

---

---

Recurrent Proximal Weakness — Viva-Style Deep Dive

---

Q1. What are the major categories causing recurrent (episodic) proximal weakness?

---

SECTION 1: CHANNELOPATHIES

Q2. Classify the skeletal muscle channelopathies

CHANNELOPATHIES
├── CALCIUM CHANNEL (CACNA1S)
│   └── Hypokalemic Periodic Paralysis Type 1 (HypoPP-1) — most common
├── SODIUM CHANNEL (SCN4A)
│   ├── Hyperkalemic Periodic Paralysis (HyperKPP)
│   ├── Hypokalemic Periodic Paralysis Type 2 (HypoPP-2)
│   ├── Paramyotonia Congenita (PMC)
│   └── Potassium-Aggravated Myotonia (PAM)
├── CHLORIDE CHANNEL (CLCN1)
│   ├── Myotonia Congenita — Thomsen (AD)
│   └── Myotonia Congenita — Becker (AR)
└── POTASSIUM CHANNEL (KCNJ2)
    └── Andersen-Tawil Syndrome (ATS)

---

Q3. Differentiate HypoPP vs HyperKPP clinically

"In hypoPP, total body K⁺ is not depleted — it has shifted intracellularly; so K⁺ replacement must be cautious to avoid rebound hyperkalemia." — Rosen's Emergency Medicine

---

Q4. What is Paramyotonia Congenita (PMC) — how does it differ?

• Mutation: SCN4A (Na⁺ channel gain-of-function)
• Myotonia that WORSENS with activity and cold — opposite of warm-up phenomenon
• Episodic paralysis can follow prolonged cold exposure
• Key exam distinction: Myotonia congenita → warm-up ✅ | Paramyotonia → warm-up ❌ (worsens)
• Exercise test: Short exercise → no drop in CMAP amplitude; Long exercise + cold → CMAP drops

---

Q5. Andersen-Tawil Syndrome (ATS) — "TRIAD"?

1. Periodic paralysis (hypo, hyper or normokalemic)
2. Cardiac arrhythmias — prolonged QT, U waves, bidirectional VT → sudden cardiac death
3. Dysmorphic features — low-set ears, hypertelorism, micrognathia, short stature, clinodactyly

KCNJ2 mutation (Kir2.1 potassium channel). Many patients need ICD implantation.

---

SECTION 2: METABOLIC MYOPATHIES

Q6. How do metabolic myopathies present with recurrent proximal weakness?

---

Q7. Ischemic Forearm Exercise Test — what does it show?

Note: Non-ischemic version (without BP cuff) now preferred to avoid rhabdomyolysis.

---

SECTION 3: NMJ DISORDERS

Q8. Differentiate Myasthenia Gravis vs Lambert-Eaton Myasthenic Syndrome (LEMS)

---

Q9. Describe the RNS (Repetitive Nerve Stimulation) pattern

                    MG                          LEMS
Low Hz (3Hz):   DECREMENTAL ↓↓↓↓↓          DECREMENTAL ↓↓↓↓↓
High Hz (50Hz): No increment               INCREMENTAL ↑↑↑↑ (>100%)
Post-exercise:  Repair of decrement        Marked increment (facilitation)
               (brief) then post-activation 
               exhaustion after 3-4 min

---

SECTION 4: CLINICAL DIFFERENTIATION TABLE (MASTER)

---

SECTION 5: INVESTIGATION ALGORITHM

Q10. How do you investigate recurrent proximal weakness?

• Serum K⁺ (critical — determines channelopathy subtype)
• ECG (hypoK → U waves; hyperK → peaked T)
• Serum CK (markedly elevated → metabolic; mildly elevated → inflammatory/dystrophic)
• Urine for myoglobin (rhabdomyolysis → McArdle, CPT II)
• Thyroid function (TSH, T₃, T₄) — if first episode of HypoKPP

---

SECTION 6: HIGH-YIELD VIVA QUICK-FIRES

• Succinylcholine → triggers myotonia/myotonic crisis in all myotonias; prolonged muscle rigidity
• Volatile agents (halothane, isoflurane) → can trigger hyperKPP attacks (membrane depolarization)
• NMBDs: both depolarizing and non-depolarizing should be used cautiously in LEMS (profound sensitivity)

---