DEVELOPMENT OF LARYNX AND LARYNGEAL WEB

(RGUHS University - 20 Mark Answer)

PART A: DEVELOPMENT OF LARYNX

I. EMBRYOLOGICAL TIMELINE AT A GLANCE

WEEK 4:   Laryngotracheal groove forms in floor of primordial pharynx
           ↓
WEEK 4:   LT diverticulum evaginates; lung bud appears
           ↓
WEEK 5:   Tracheoesophageal septum divides foregut → LT tube (ventral) + esophagus (dorsal)
           ↓
WEEK 5-6: Arytenoid swellings appear → primordial glottis = T-shaped inlet
           ↓
WEEK 6-8: Epithelial proliferation → TEMPORARY OCCLUSION of laryngeal lumen
           ↓
WEEK 10:  RECANALIZATION → laryngeal ventricles form → vocal folds + vestibular folds
           ↓
BIRTH:    High larynx in neonate; descends over first 2 years of life

II. ORIGIN OF LARYNGEAL STRUCTURES

┌─────────────────────────────────────────────────────────────────────┐
│              SOURCES OF LARYNGEAL COMPONENTS                        │
├──────────────────────────────┬──────────────────────────────────────┤
│  Structure                   │  Embryological Origin               │
├──────────────────────────────┼──────────────────────────────────────┤
│  Epithelial lining           │  Endoderm of cranial LT tube        │
│  Glands of larynx            │  Endoderm                           │
│  Cartilages (thyroid,        │  Mesenchyme from 4th & 6th          │
│  cricoid, arytenoid,         │  pharyngeal arches (neural crest    │
│  cuneiform, corniculate)     │  derived)                           │
│  Epiglottis                  │  Hypopharyngeal eminence            │
│                              │  (3rd + 4th arch ventral ends)      │
│  Cricothyroid muscle         │  4th pharyngeal arch myoblasts      │
│  All other intrinsic         │  6th pharyngeal arch myoblasts      │
│  laryngeal muscles           │                                     │
│  Connective tissue,          │  Splanchnic mesoderm surrounding    │
│  smooth muscle               │  the foregut                       │
│  Vasculature                 │  Splanchnic mesenchyme              │
└──────────────────────────────┴──────────────────────────────────────┘

III. STEP-BY-STEP DEVELOPMENT (DETAILED)

STEP 1 - Respiratory Primordium (Week 4)

• The Developing Human, p. 565

STEP 2 - Laryngotracheal Diverticulum (End of Week 4)

STEP 3 - Tracheoesophageal Septum (Week 5)

• Ventral portion = laryngotracheal tube (larynx, trachea, bronchi, lungs)
• Dorsal portion = primordium of oropharynx and esophagus

• The Developing Human, p. 567-568

STEP 4 - Arytenoid Swellings (Weeks 5-6)

• Grow toward the tongue
• Convert the slit-like primordial glottis → T-shaped laryngeal inlet
• Reduce the developing laryngeal lumen to a narrow slit
• Elongate cranially, creating a cleft bounded laterally by aryepiglottic folds

STEP 5 - Temporary Occlusion (Weeks 6-10)

STEP 6 - Recanalization (Week 10)

• Laryngeal ventricles form (recesses of mucous membrane)
• True vocal folds (cords) emerge as folds of mucous membrane
• Vestibular folds (false cords) form similarly
• Cummings Otolaryngology, p. 3940; The Developing Human, p. 570

Epiglottis Development

STEP 7 - Innervation

• 4th arch (cricothyroid) → Superior laryngeal nerve (SLN) (branch of CN X)
• 6th arch (all other intrinsic muscles) → Recurrent laryngeal nerve (RLN) (branch of CN X)

Position of Larynx

• The Developing Human, p. 571

IV. DIAGRAM - DEVELOPMENT OF LARYNX (Successive stages)

PART B: LARYNGEAL WEB (DETAILED - 20 Marks)

I. DEFINITION

• Scott-Brown's Vol 2, p. 523
• Cummings Otolaryngology, p. 3895
• K.J. Lee's Essential Otolaryngology, p. 939

II. CLASSIFICATION

┌────────┬────────────────────────┬──────────────────────────────────┬─────────────────────────────────┐
│ Grade  │ Glottic Obstruction    │ Subglottic Involvement           │ Symptoms                        │
├────────┼────────────────────────┼──────────────────────────────────┼─────────────────────────────────┤
│ Type 1 │ < 35%                  │ None or little                   │ Mild hoarseness only            │
│ Type 2 │ 35% – 50%              │ Thin anterior web, little        │ Hoarse/weak cry, stridor on     │
│        │                        │ subglottic extension             │ exertion                        │
│ Type 3 │ 50% – 75%              │ Thin-thick web, extends to       │ Severe hoarseness, moderate     │
│        │                        │ lower border of cricoid          │ airway obstruction              │
│ Type 4 │ > 75%                  │ Thick web to below cricoid;      │ Aphonia, severe obstruction     │
│        │                        │ subglottic "sail" configuration  │ Neonatal emergency              │
└────────┴────────────────────────┴──────────────────────────────────┴─────────────────────────────────┘

III. EMBRYOLOGICAL BASIS (PATHOGENESIS)

FLOWCHART: PATHOGENESIS OF CONGENITAL LARYNGEAL WEB

Normal Development:
Laryngeal lumen occluded (Wk 6-8)
        ↓
Vacuolization & Recanalization (Wk 10)
        ↓
Complete recanalization → NORMAL LARYNX

Abnormal Development:
FAILURE / INCOMPLETE RECANALIZATION (Week 10)
        ↓
        ├──► Partial failure → LARYNGEAL WEB (connective tissue 
        │                      covered with mucous membrane)
        └──► Complete failure → LARYNGEAL ATRESIA (CHAOS Syndrome)

IV. INCIDENCE AND ASSOCIATIONS

• Rare - estimated 1:10,000 - 1:70,000 live births (Dhingra; Hazarika)
• More common in males
• 22q11.2 deletion syndrome is the most important association:
  • In one series of 17 patients with anterior glottic webs, 11 (65%) had chromosome 22q11.2 deletions (Cummings, p. 3895)
  • Phenotypes include: DiGeorge syndrome, Velocardiofacial (Shprintzen) syndrome, conotruncal heart malformations
• Richieri-Costa Pereira syndrome: laryngeal anomalies including microwebs, hypoplasia of epiglottis
• Cardiac anomalies are frequently associated - all patients require thorough cardiovascular evaluation including aortic arch assessment (vascular ring may mimic laryngeal web symptoms)
• Associated chromosomal and cardiac anomalies reported by multiple authors (Stell & Maran)

V. CLINICAL FEATURES

FLOWCHART: CLINICAL PRESENTATION BASED ON GRADE

                LARYNGEAL WEB
                     │
      ┌──────────────┼──────────────┐
      ▼              ▼              ▼
   GRADE I        GRADE II      GRADE III/IV
      │              │              │
  Mild hoarse    Weak/hoarse   Severe airway
   voice only    cry, exertional  obstruction +
  May be          stridor        aphonia +
  incidental                    neonatal
  finding                       emergency

1. Weak, hoarse cry from birth - pathognomonic
2. Inspiratory stridor - characteristically high-pitched
3. Squeaky, high-pitched voice - characteristic
4. Respiratory distress - degree depends on grade
5. Aphonia - in severe types (Grade IV)
6. Recurrent croup in infancy - combination of weak cry from birth + recurrent croup should always raise suspicion (Scott-Brown, p. 536)
7. Thin webs may be lysed unrecognized during intubation

VI. DIAGNOSIS

DIAGNOSTIC ALGORITHM FOR SUSPECTED LARYNGEAL WEB

Neonate/Child with:
Weak cry + Stridor + Hoarse voice
           │
           ▼
AWAKE FLEXIBLE NASOPHARYNGOSCOPY (First investigation)
           │
     ┌─────┴──────┐
     │            │
  Web seen    Inconclusive
     │            │
     ▼            ▼
MICROLARYNGOSCOPY    CT Neck/Chest
& BRONCHOSCOPY       (assess subglottic
(Gold standard)       extent, vascular ring)
     │
     ├── Confirm grade (Cohen classification)
     ├── Assess subglottic extension
     ├── Assess associated lesions
     └── Thickness of web (thin vs cartilaginous)
           │
           ▼
   GENETIC SCREENING (22q11.2 FISH/microarray)
   ECHOCARDIOGRAPHY (cardiovascular anomalies)

• Anterior grayish-white membrane across the anterior glottis
• Thin posteriorly near free edge, thicker anteriorly
• "Sail" configuration of subglottis in Grade 3/4 (Cummings)
• Grade determines extent and need for open vs. endoscopic surgery

VII. TREATMENT

TREATMENT FLOWCHART FOR LARYNGEAL WEB

                LARYNGEAL WEB DIAGNOSED
                          │
               ┌──────────┴───────────┐
               │                      │
         GRADE I/II              GRADE III/IV
         (< 50% obstruction)     (> 50% obstruction)
               │                      │
               ▼                      ▼
    Small, thin, asymptomatic?   TRACHEOSTOMY first
               │                (to secure airway)
        ┌──────┤                      │
        │      │                      ▼
     Yes       No            LARYNGOTRACHEAL RECONSTRUCTION (LTR)
        │      │              - Anterior cartilage graft
        ▼      ▼              - Laryngofissure + stent/keel
  CONSERVATIVE  ENDOSCOPIC     or
  (observe)    APPROACH:    OPEN APPROACH:
               - Cold knife    - Thyrotomy + keel
               division        placement (Montgomery
               - CO2 laser     keel)
               division       - LTR with cartilage
               - Keel          grafting
               placement      - Cricotracheal resection
               (endoscopic)    (in selected cases)

1. Conservative (Grade I, minimal symptoms)

• No intervention needed for very small, asymptomatic webs
• Regular follow-up

2. Endoscopic Lysis (Grade I and selected Grade II)

• Division with cold knife or CO2 laser along margin of one vocal cord
• Keel placement endoscopically after division to prevent re-web formation
• If web is very thin: subsequent endoscopic dilation may be sufficient
• In young children with small larynx: covering tracheostomy is required for 2 weeks while keel is in place
• Scott-Brown's Vol 2, p. 550-564

3. Open Surgery (Grade III and IV)

• Laryngotracheal reconstruction (LTR) with anterior cartilage grafting
• Can be done as single-stage (infant, post-op ETT stenting 5-7 days) or double-stage (tracheostomy first, LTR at 1-2 years when larynx is larger)
• Laryngofissure with keel (Montgomery keel) placement
• Voice outcomes after repair are often less favorable, particularly with multiple/revision procedures
• Cummings, p. 3895-3896

4. EXIT Procedure (Grade IV, Laryngeal Atresia/CHAOS)

• Ex utero intrapartum treatment (EXIT): airway secured before delivery is complete
• Prenatal diagnosis via fetal MRI (enlarged echogenic lungs, inverted diaphragms, massive ascites, dilated airways)
• Cummings, p. 3896

VIII. SPECIAL ENTITY: LARYNGEAL ATRESIA AND CHAOS SYNDROME

CHAOS SYNDROME (Congenital High Airway Obstruction Syndrome)
                    │
          Complete failure of recanalization
                    │
          ┌─────────┼─────────────┐
          ▼         ▼             ▼
    Laryngeal   Subglottic    Tracheal
    atresia     atresia       atresia
          │
          ▼
  PRENATAL FEATURES (on USS/MRI):
  - Enlarged echogenic lungs
  - Inverted diaphragm
  - Dilated airways distal to obstruction
  - Fetal ascites/hydrops
          │
          ▼
  POSTNATAL: Aphonia + extreme respiratory
  distress + cyanosis at birth
          │
          ▼
  MANAGEMENT: EXIT procedure (ex utero 
  intrapartum treatment) + tracheostomy

IX. ACQUIRED LARYNGEAL WEB

• Post-intubation trauma (commonest acquired cause)
• Post-surgical (after laryngeal procedures, irradiation)
• Inflammatory (diphtheria, syphilis, lupus)
• Post-laryngeal injury

X. RECENT ADVANCES (2021-2026)

1. Prenatal diagnosis - fetal MRI for CHAOS/laryngeal atresia with EXIT procedure planning improving survival
2. Genetic testing - routine 22q11.2 microarray in all congenital laryngeal webs
3. KTP and CO2 laser techniques - office-based angiolytic laser (KTP 532nm) for thinner webs
4. Balloon dilation - as adjunct after endoscopic lysis
5. Mitomycin C application post-lysis to reduce re-web formation (some centers)
6. 3D endoscopic imaging and narrow-band imaging for better characterization
7. Tissue-engineered scaffolds - experimental, for LTR grafts

XI. PROGNOSIS

• Voice outcomes are often suboptimal even after successful airway reconstruction
• Grade I/II: Good prognosis for both airway and voice
• Grade III/IV: Airway patency is achievable; voice may remain permanently impaired
• Multiple/revision procedures worsen voice outcome
• Associated 22q11.2 deletion may affect overall prognosis due to cardiac/immune issues

SUMMARY TABLE (Quick Revision for RGUHS)

REFERENCES FOR RGUHS ANSWER

1. Cummings Otolaryngology Head and Neck Surgery - Chapter 206 (Congenital Laryngeal Anomalies) & Chapter 209 (Laryngeal Stenosis)
2. Scott-Brown's Otorhinolaryngology Head & Neck Surgery Vol 2 - Chapter 30 (Paediatric Laryngeal Conditions)
3. K.J. Lee's Essential Otolaryngology - Chapter: Developmental Anatomy / Laryngeal Web or Atresia
4. The Developing Human - Clinically Oriented Embryology (Moore & Persaud) - Chapter 10: Respiratory System (Development of Larynx, pp. 570-572)
5. Dhingra PL - Diseases of Ear, Nose and Throat - Chapter on Congenital Laryngeal Anomalies
6. Hazarika P - Textbook of Ear Nose Throat & Head Neck Surgery - Chapter on Larynx
7. Stell & Maran's Head and Neck Surgery - Relevant chapter on Laryngeal Anomalies
8. Cohen SR - Congenital glottic webs in children: a retrospective review of 51 patients. Ann Otol Rhinol Laryngol Suppl 121:2-16, 1985 (ORIGINAL CLASSIFICATION)
9. Moore AE, Walker A, Kanotra SP - Endoscopic Versus Open Surgical Intervention for Congenital Laryngeal Webs: A Systematic Review and Meta-Analysis. Otolaryngol Head Neck Surg 2023 Aug; PMID: 36939597 (Level 1 Evidence)

RGUHS Exam Tip: For a 20-mark question, structure your answer as: (1) Development of Larynx with flowchart of stages (6 marks), (2) Definition + Classification of Laryngeal Web with Cohen table (4 marks), (3) Etiology + Pathogenesis flowchart (2 marks), (4) Clinical features + Diagnosis flowchart (4 marks), (5) Treatment flowchart with management algorithm (4 marks). Always mention 22q11.2 association, Cohen classification, and EXIT procedure for full marks.