| Crouzon syndrome | |
|---|---|
| Other names | Branchial arch syndrome |
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| Baby with Crouzon syndrome | |
| Specialty | Medical genetics |
Crouzon syndrome is anautosomal dominant genetic disorder known as abranchial arch syndrome. Specifically, this syndrome affects thefirst branchial (or pharyngeal) arch, which is the precursor of themaxilla andmandible. Because the branchial arches are important developmental features in a growingembryo, disturbances in their development create lasting and widespread effects. The syndrome is caused by a mutation in agene onchromosome 10 that controls the body's production offibroblast growth factor receptor 2 (FGFR2).
Crouzon syndrome is named forOctave Crouzon,[1][2] aFrenchphysician who first described this disorder. First called "craniofacial dysostosis" ("craniofacial" refers to theskull andface, and "dysostosis" refers to malformation of bone), the disorder was characterized by a number of clinical features which can be described by the rudimentary meanings of its former name. The developing fetus's skull and facial bones fuse early or are unable to expand. Thus, normal bone growth cannot occur. Fusion of different sutures leads to abnormal patterns of growth of the skull.
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A defining characteristic of Crouzon syndrome iscraniosynostosis, which results in an abnormal head shape. This is present in combinations of:frontal bossing,trigonocephaly (fusion of themetopic suture),brachycephaly (fusion of the coronal suture),dolichocephaly (fusion of thesagittal suture),plagiocephaly (unilateral premature closure oflambdoid andcoronal sutures),oxycephaly (fusion ofcoronal andlambdoidal sutures), and complexcraniosynostosis (premature closure of some or all sutures).[citation needed]
Exophthalmos (bulgingeyes due to shallow eye sockets after early fusion of surrounding bones),hypertelorism (greater than normal distance between the eyes), andpsittichorhina (beak-like nose) are also very common features. Other facial characteristics that are present in many cases include externalstrabismus andhypoplastic maxilla (insufficient growth of the midface), which results in relativemandibular prognathism (protruding chin) and gives the effect of the patient having a concave face.[3]
Most symptoms are secondary to the abnormal skull structure. Approximately 30% of people with Crouzon syndrome develophydrocephalus.Sensorineural hearing loss is present in some cases. The abnormalities in the manner in which the eyes fit in the eye sockets can cause vision problems, the most common of which is corneal exposure that can lead to visual impairment.[4] Some people with the condition have a restricted airway and can experience severe problems breathing.[5]
Common features are a narrow/high-arched palate, posterior bilateral crossbite,hypodontia (missing some teeth), and crowding of teeth. Due to maxillary hypoplasia, people with Crouzon syndrome generally have a considerable permanentunderbite.[6]
The current research indicatesfibroblast growth factor receptors (FGFR)FGFR2 andFGFR3 as the leading factors in causing the autosomal dominant Crouzon syndrome.[7][8] These twotransmembrane proteins are two of four fibroblast growth factor receptors involved inosteoblastdifferentiation duringembryonic development; mutations amongst these receptors are involved in several genetic disorders.[7]
There are 40 known mutations, most of which are caused by amissense mutation.[9] FGFR2 is the most commonly mutated gene, a missense atcysteine 342 inexon 9, which creates a gain-of-function.[9] The FGFR2lllcisoform, created viaalternative splicing of exon 3 of the FGFR2 gene, uses exon 9 and is used inmesenchymal stem cells to controlossification. However, the mutationconstitutively activates the transmembrane protein via adisulfide bond formed incorrectly due to the loss of cysteine 342.[9] FGFR3 is expressed more in thefrontal bones during embryonic development, guiding cranial bone development. A point mutation causes constitutive activation oftyrosine in the activation loop, located in thecytosolic region of the protein, leading to accelerated differentiation of frontal osteoblasts,[10] resulting in premature fusion of frontal cranial bones.[10]
Diagnosis of Crouzon syndrome usually can occur at birth by assessing the physical appearance of the infant. Further analysis, including radiographs,magnetic resonance imaging (MRI) scans,genetic testing and CT scans can be used to confirm the diagnosis of Crouzon syndrome.[citation needed]
Surgery is typically used to prevent the closure of sutures of the skull from damaging the brain's development. Without surgery,blindness andintellectual disability are typical outcomes. Without treatment, Crouzon syndrome can cause hearing and vision loss, exposure keratitis or conjunctivitis, drying of the cornea, hydrocephalus, sleep apnea, and breathing problems.[medical citation needed] To move the orbits forward, surgeons expose the skull and orbits and reshape the bone. To treat the midface deficiency, surgeons can move the lower orbit and midface bones forward.[medical citation needed] Additionally, surgery can be performed to relieve pressure inside the skull, fix a cleft lip or palate, correct a malformed jaw, straighten crooked teeth, or correct eye problems.[medical citation needed]
People with Crouzon syndrome tend to have multiple sutures involved, most specifically bilateral coronalcraniosynostoses, and either open vault surgery or strip craniectomy (if the child is under 6 months) can be performed. In the latter scenario, a helmet is worn for several months following surgery.[citation needed]
Once treated for the cranial vault abnormalities, Crouzon patients generally go on to live a normal lifespan.[citation needed]
Incidence of Crouzon syndrome is currently estimated at 1.6 out of every 100,000 people.[11] It is the most common craniostenosis syndrome.[8]
Crouzon syndrome was first described byOctave Crouzon in 1912.[12] He noted the affected patients were a mother and her daughter, implying a genetic basis.[citation needed]
