Genomic coordinate (human 10:121,478,330 FGFR2) & (mouse 7:129,764,181 Fgfr2).
Cytoband (human 10q26.13 FGFR2) & (mouse 7qF3 Fgfr2).
Here I present: “Crouzon Syndrome“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (FGFR2) icd10=Q75.1
Crouzon syndrome is a genetic disorder characterized primarily by premature fusion of certain skull bones, a condition known as craniosynostosis. This early fusion affects the shape of the head and face. It is one of the more common craniosynostosis syndromes. Here’s a detailed overview:
Genetics:
Inheritance: Autosomal dominant (one copy of the mutated gene is sufficient).
Gene involved: FGFR2 (Fibroblast Growth Factor Receptor-2).
Mutation effect: Causes abnormal signaling in bone development, leading to early fusion of skull sutures.
Clinical Features:
Craniofacial Abnormalities:
Brachycephaly (short, wide head) or scaphocephaly (long, narrow head) depending on sutures fused.
Exophthalmos (bulging eyes) due to shallow eye sockets.
Hypertelorism (wide-set eyes).
Beaked nose or midface hypoplasia (underdeveloped midface).
Mandible often normal, so sometimes class III malocclusion (underbite).
Neurological:
Usually normal intelligence.
Rarely, hydrocephalus or increased intracranial pressure if multiple sutures fused early.
Other Features:
Hearing loss in some patients (due to middle ear abnormalities).
Sometimes dental crowding or cleft palate.
Normal extremities (unlike some other craniosynostosis syndromes, e.g., Apert syndrome).
Diagnosis.
Clinical examination: Characteristic facial features and head shape.
Imaging:
X-ray or CT scan of the skull showing premature suture fusion.
Genetic testing: Confirms FGFR2 mutation.
Management.
Surgical: Mainstay treatment to correct skull shape and prevent intracranial pressure.
Cranial vault remodeling in infancy.
Midface advancement later for facial function and aesthetics.
Supportive:
Eye care for exposure keratitis (if eyes protrude significantly).
Dental and orthodontic treatment.
Hearing evaluation and intervention if needed.
Prognosis.
With modern surgical interventions, most patients have a normal life expectancy and intelligence.
Early intervention helps prevent complications like vision loss or intracranial hypertension.
There is evidence that Crouzon syndrome is caused by mutation in the fibroblast growth factor receptor-2 (FGFR2) gene encoded on genomic coordinate 10:121,478,330 and cytoband 10q26.13 in humans.
