SEARCH RESULTS FOR: Apert-Syndrome

Apert Syndrome

Apert Syndrome: Pathogenesis and clinical findings Gain of function mutation in fibroblast growth factor 2 receptor (FGFR2) on chromosome 10q Mutated FGFR2 protein has ↑ ligand binding & signalling activity Osteoblasts undergo early differentiation & maturation in response to ↑ FGFR2 ↑ Bone deposition & ossification Osteoblast progenitors proliferate at ↑ rate Abnormal mesenchymal differentiation in response to ↑ FGFR2 Authors: Merry Faye Graff, Taylor Krawec Reviewers: Emily J. Doucette, Ryan Frank* * Indicates MD at time of publication Apert Syndrome (Acrocephalosyndactyly Type I) A rare genetic disorder characterized by multisuture craniosynostosis, midface retrusion, & syndactyly of the hands & feet Craniofacial Abnormalities Premature differentiation of neural crest-derived mesenchyme in face Underdevelopment of midfacial bones (e.g. maxilla, zygoma) Orbit growth is rotated outward Extraocular muscles insert anomalously ↓ Control of eye movement Mesenchymal cells at palatal shelf undergo abnormal differentiation Palatal midline epithelial seam fails to undergo apoptosis Premature osteoblast maturation in suture mesenchyme Midface hypoplasia Hypertelorism (widely separated orbits) V-pattern exotropia (“V” shaped eye movement) ↓ Palatal shelf outgrowth & misalignment Bicoronal synostosis (premature fusion of coronal sutures) Shallow orbits displace globes forward Depressed nasal bridge ↓ Length of hard palate Abnormal eustachian tube development ↓ Anteroposterior growth of nasal cavity Cleft palate** Fusion of coronal sutures restricts anteroposterior skull growth Exorbitism (protruding eyes) Beaked nose ↓ Drainage of middle ear Choanal stenosis (narrowed nasal passages) Skull grows vertically as brain develops Cerebral spinal fluid accumulates in ventricles Incomplete eyelid closure ↑ corneal exposure & damage Class III malocclusion (underbite) V shaped dental arch High arched palate Recurrent ear effusions ↑ Nasal canal obstruction Breathing difficulty Turribrachycephaly (tower shaped skull) Ventriculomegaly (↑ ventricular size) Corneal scarring Exposure keratopathy Impaired ossicle function Conductive hearing loss Brain growth is restricted Developmental delay Limb & Skeletal Abnormalities Phalanges of fingers &/or toes undergo premature ossification ↑ Proliferation in apical ectodermal ridge at distal limb bud during embryonic development ↓ Regression of interdigital mesenchyme allow persistence of interdigital soft tissue bridges Other Abnormalities FGFR2 mutation leads to sebaceous gland hyperplasia & follicular keratinization Excess sebum production & follicular blockage Osseus syndactyly Legend: ↑ FGFR2 alters BMP & SHH signaling balance Pathophysiology Mechanism Sign/Symptom/Lab Finding Cutaneous syndactyly (may include nailbed) Severe acne Published Sept 16, 2025 on www.thecalgaryguide.com Complications