Pierre Robin sequence

**Definition:** A "sequence" is a cascade of anomalies that arise from a single initiating defect. In PRS, the initiating event is mandibular hypoplasia (micrognathia/retrognathia) before about 9-10 weeks of gestation.

**Pathophysiology (the sequence):** 1. Early mandibular hypoplasia (from intrinsic growth failure or intrauterine constraint) leaves the tongue positioned posteriorly (glossoptosis). 2. The posteriorly placed tongue sits between the palatal shelves and prevents their fusion. This produces a wide, U-shaped cleft of the posterior palate. A V-shaped cleft is more typical of isolated cleft palate. 3. The tongue and small mandible narrow the oropharynx, causing upper airway obstruction.

**Clinical features:** - Micrognathia with a receding chin - Glossoptosis - Cleft palate, present in about 80-90% of cases - Respiratory distress, stridor, and snoring, which are worse when the infant is supine or feeding - Feeding difficulty and failure to thrive - Possible complications: cor pulmonale, chronic hypoxia, and aspiration

**Associations:** - About 50% of cases are syndromic. The most common association is **Stickler syndrome** (COL2A1 mutation, a type II collagen defect). It causes myopia, retinal detachment, hearing loss, and joint hypermobility or early arthritis. - Other associations are 22q11.2 deletion (velocardiofacial/DiGeorge syndrome), Treacher Collins syndrome, fetal alcohol syndrome, and campomelic dysplasia (SOX9). - The isolated form is often linked to SOX9 regulatory-region variants. - Oligohydramnios or fetal crowding is a proposed mechanical cause. - Related first-arch syndromes (Treacher Collins, Goldenhar) can look similar, so know the distinguishing features.

**Diagnosis:** Clinical, based on the physical exam. Prenatal ultrasound may show micrognathia or polyhydramnios. Evaluate for associated syndromes with an ophthalmology exam, echocardiogram, hearing screen, and genetic testing as indicated.

**Management:** - Conservative first-line care is prone or lateral positioning, which lets the tongue fall forward. - Other options are a nasopharyngeal airway and specialized feeding techniques or nipples. A nasogastric tube may be needed. - Severe cases may need mandibular distraction osteogenesis, tongue-lip adhesion, or tracheostomy. - Cleft palate repair is done at about 6-12 months. - Mandibular catch-up growth often occurs in the first few years, and the airway usually improves with age.

**Board pearls:** - Classic vignette: a newborn with a small jaw, a tongue that falls back, and respiratory distress that improves when prone. - The cleft palate is U-shaped. - Think of Stickler syndrome as the most common associated syndrome. - It is a *sequence*, not a syndrome: a single primary defect (micrognathia) causes the downstream findings. - Do not confuse it with Treacher Collins (TCOF1, neural crest defect, with downslanting palpebral fissures and malar hypoplasia).