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Crouzon Syndrome

Crouzon Disease

Crouzon disease is an autosomal dominant disorder characterized by craniosynostosis and facial hypoplasia.


Presentation

According to history findings [8]:

The physical findings show the following:

  • Fontanels stay unobliterated and pulsating for a long time while coronal and sagittal sutures are obliterated.
  • Anteroposterior and lateral flattening of the acrocranium is observed with growth only along the vertical axis.
  • The transverse diameter is bigger than the anteroposterior diameter.
  • The forehead is often high and wide.
  • There is the presence of hypoplastic maxilla producing pseudoprognathism and a wide face.
  • Narrowed or obliterated anterior nares and deviation of the nasal septum is present.
  • Hypertelorism, falling upper eyelid and divergent squint is also observed.
  • The upper lip is often shortened and cleaved in some cases.
  • Due to intracranial hypertension, vision impairment occurs due to progressive optic nerve atrophy.
  • Disorders of the middle ear brings about impaired hearing.
  • Dysphasia, rhinolalia, hypsistaphylia (narrow/high-arched palate), malposed teeth and malocclusion are noted in many cases.
  • Characteropathy is a common observation.
  • Koilosternia occurs rarely.
  • Skin of the individual is darker than normal.
  • In childhood, syndromic acanthosis nigricans appears in axillary fossa, on the lips and mouth angular.
Broad Thumb
  • We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome.[ncbi.nlm.nih.gov]
  • thumbs, thus giving the hands a mitten-like appearance, and short higher extremity.[whonamedit.com]
Severe Pain
  • The patient, an 11 year old boy with grossly carious teeth and in severe pain was referred for dental treatment. A review of literature on Crouzon Syndrome is presented.[ncbi.nlm.nih.gov]
Sepsis
  • Risk factors associated with the development of venous thromboembolic events in pediatric patients include the use of central venous catheters, hospitalization, cancer, sepsis, trauma, surgery, and congenital prothrombotic disorders.The authors present[ncbi.nlm.nih.gov]
Pseudotumor
  • A 25-year-old man with Crouzon syndrome complicated by pseudotumor cerebri and multiple shunt failures presented with progressive back and neck pain, intermittent headaches, and associated vomiting secondary to shunt infection.[ncbi.nlm.nih.gov]
Stridor
  • She needed intubation at age 1 month, and repeated trials of extubation failed because of marked respiratory distress, stridor, and severe expiratory obstruction and wheezing.[ncbi.nlm.nih.gov]
Cutaneous Manifestation
  • We report 6 cases and summarize the existing literature with regard to the cutaneous manifestations of this disorder. All patients have widespread, early-onset acanthosis nigricans.[ncbi.nlm.nih.gov]
Hearing Impairment
  • A 24-year-old woman visited our department for evaluation of persistent hearing impairment and absence of an external auditory canal from birth.[ncbi.nlm.nih.gov]
  • Hearing impairment may occur. The syndrome varies in severity from mild to very serious.[mun-h-center.se]
  • impairment Breathing problems Diagnosis Diagnosis of Crouzon syndrome requires a combination of measures.[ana-neurosurgery.com]
  • The condition may also affect internal structures, which causes varying degrees of hearing impairment. In 5 to 10 percent of the cases, children also have dark, roughened folds of skin located in the armpits or groin.[craniofacial.net]
  • Signs and symptoms of Crouzon syndrome may include wide-set, bulging eyes; strabismus (misalignment of the eyes); a small, "beak-shaped" nose; and an underdeveloped upper jaw. 0001321 Conductive hearing impairment Conductive deafness Conductive hearing[rarediseases.info.nih.gov]
Blue Sclera
  • Other associations are aniridia, blue sclera, cataract, coloboma, ectopia lentis and optic nerve hypoplasia. No medical treatment exists for craniosynostosis.[casereports.bmj.com]
  • There also have been rare occurances of nystagmus, iris coloboma, aniridia, anisocoria, microcornea, megalocornea, cataract, ectopia lentis, blue sclera, glaucoma and luxation of the eye ( Bowling and Burstein, 2006 ).[scialert.net]
  • There rarely may occur nystagmus, coloboma of the iris, anisocoria, microcornea or megalocornea, cataract, blue sclerae, glaucoma and globe luxation (6).[arquivosdeorl.org.br]
Skeletal Dysplasia
  • Dysplasia Society, Southeastern Regional Genetics Group Disclosure: Nothing to disclose.[emedicine.com]
Neck Pain
  • A 25-year-old man with Crouzon syndrome complicated by pseudotumor cerebri and multiple shunt failures presented with progressive back and neck pain, intermittent headaches, and associated vomiting secondary to shunt infection.[ncbi.nlm.nih.gov]
Headache
  • The authors present a patient with CS who underwent posterior cranial vault reconstruction with internal distraction after multiple episodes of headache and papilledema.[ncbi.nlm.nih.gov]
  • A 25-year-old man with Crouzon syndrome complicated by pseudotumor cerebri and multiple shunt failures presented with progressive back and neck pain, intermittent headaches, and associated vomiting secondary to shunt infection.[ncbi.nlm.nih.gov]
  • The authors report on the case of a 15-year-old boy with Crouzon syndrome (CS) who presented with headache and facial diplegia.[ncbi.nlm.nih.gov]
  • Symptoms of this pressure include headaches, vomiting, lack of appetite, and damage to the optic nerve. Hearing impairment may occur. The syndrome varies in severity from mild to very serious.[mun-h-center.se]
  • Occasionally, patients may experience frequent headaches or seizures.[chla.org]
Papilledema
  • We present a case of a 5-year-old girl with Crouzon syndrome displaying classic facial abnormalities along with proptosis and papilledema. The child's condition was improved dramatically after a monoblock advancement procedure.[ncbi.nlm.nih.gov]
  • The authors present a patient with CS who underwent posterior cranial vault reconstruction with internal distraction after multiple episodes of headache and papilledema.[ncbi.nlm.nih.gov]
  • The neuroophthalmological examination revealed neither papilledema nor oculomotor palsy. Electromyography confirmed incomplete peripheral facial diplegia.[ncbi.nlm.nih.gov]

Workup

Histopathologic examination of changes in the skin will often reveal acanthosis nigricans [9]. To confirm the diagnosis, hand, spine and skull radiography is often required. The skull radiography will reveal the following:

  • Underdeveloped lateral nasal sinuses
  • Shortened anterior cranial fossa
  • Presence of Turkish saddle which is deepened with osseous sternum which connects the anterior and posterior clinoid processes.
  • Shallow eye sockets (exophthalmous) and deep digitate impression.
  • Obliterated sutures (usually the sagittal and coronal) and Oxycephaly-Acrocranium

On radiography of the spine, lumbarization and the presence of bifid spinous process is seen. Some cases show signs of achondroplasia too. Achondroplasia is also established by looking through a radiographic examination of the metacarpal bones and fingers.

Other tests can also be carried out to further confirm diagnosis. These tests include:

  • Psychiatric examinations and psychological testing
  • Stomatologic examination
  • Laryngologic examinations with audiography
  • Ophthalmologic examination with ophthalmoscopy
  • Genetic testing
  • General physical examination with ECG
  • EEG - Low-voltage, increased convulsive excitability

Histologic findings

Papillomatosis, acanthosis and hyperkeratosis are all histologic features of acanthosis nigricans. The amount of pigment cells is also increased in the upper dermis of the basal layer. There is no difference between the histologic features of acanthosis nigricans in its symptomatic, benign or malignant forms.

Treatment

Surgical interventions are aimed to preventing complications and correcting the craniofacial dysmorphy which can be of great benefit.

Prognosis

Individuals with the crouzon syndrome can expect to live a normal life with any life expectancy reductions.

An ophthalmologist is expected to monitor the cornea of the eye to ensure it isn’t allowed to dry out. Any dental problems can be treated successfully [10].

Etiology

The Crouzon syndrome is often inherited in an autosomal pattern. Associations with mutations in the genes FGFR2 and FGFR3 have been identified in many cases [5].

Dental significance

This disorder is of interest to dentists because many of the abnormalities recorded physically are present in the head and mostly the oral cavity. The common features are crowding of teeth, hypodontia (missing some teeth), posterior lateral crossbite and narrow/high-arched palate.

Crouzon patients have permanent underbite and thus they will not be able to chew using their incisors. The permanent underbite is as a result of maxillary hypoplasia. It is for this reason that many Crouzon patients have to eat in a way that can be deemed as unusual. Breaking off pieces of sandwich instead of taking a bite into it and eating fried chicken with a fork are some of these unusual eating habits [6].

Epidemiology

The prevalence of this condition is very low as Crouzon syndrome is very rare across the world. It is currently estimated that it occurs in 1 out of 25,000 individuals in the general population across the world [4].

Mortality/morbidity

When there is high intracranial pressure, death may occur. High intracranial pressure is brought about by disproportion between brain growth and craniostenosis.

Race

There is no difference recorded between races.

Sex

Sex does not play any role in the distribution of this condition.

Age

The deformation of bony face is readily visible just at birth and other factors linked to this syndrome become visible with time.

Sex distribution
Age distribution

Pathophysiology

All dysplasias of the skeleton which includes craniofacial dysostosis are caused by the malformations of the ectoderm and mesenchyme. This is also taking into account the unknown teratogenic factors.

Dyspalsias are inherited in an autosomal dominant pattern. The condition is believed to stem from the mutation of the gene for fibroblast growth factor receptor 2 (FGFR2) [7]. However, mutation in the transmembrane region of the FGFR3 has been detected as a possible cause of this syndrome. It has been observed in cases where acanthosis nigricans was exisiting alongside the condition.

Prevention

There are no guidelines for prevention of Crouzon syndrome.

Summary

Also known as branchial arch syndrome, Crouzon syndrome is a genetic disorder which specifically targets the first pharyngeal (branchial) arch [1]. This arch is the precursor of the maxilla and mandible.

Disturbances in the development of the arch often have lasting and widespread effect because the branchial arches are very important developmental features in a growing embryo.

Crouzon syndrome was first discovered in 1912 as one of the types of craniofacial dysotosis. The dysostosis is brought about by premature obliteration and subsequent ossification of two sutures or more. The sutures mostly affected are the sagittal and coronal. The term craniostenosis was introduced by Virchow [2]. The type of craniostenosis is determined by the type of obliterated sutures. The differentiations are, oblique head, wedge skull, scaphocephaly, and oxycephaly. The most common occurences of dysostosis involve Crouzon syndrome with Oxycephaly and Apert Syndrome with oxycephaly.

The syndrome is named after a French physician Octave Crouzon who was the first to describe this disorder. According to him, there affected patients were a mother and daughter and this implied genetic bias. It was first called craniofocal dysostosis and it is a disorder that was characterised by numerous clinical features. The syndrome occurs where there is a mutation in the fibroblast growth factor receptor II which is located on chromosome 10 [3].

To further break down the name, “dysostosis” refers to malformation of the bone while “craniofocal” refers to the skull and face.

Patient Information

Patients with Crouzon syndrome are expected to have regular appointments with an Ophthalmologist and a neurologist.

References

Article

  1. Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S (September 1994). "Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome". Nat. Genet. 8 (1): 98–103.
  2. Rutland P, Pulleyn LJ, Reardon W, et al. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet 1995; 9:173.
  3. Reardon W, Winter RM, Rutland P, et al. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 1994; 8:98.
  4. Park WJ, Meyers GA, Li X, et al. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet 1995; 4:1229.
  5. Vajo Z, Francomano CA, Wilkin DJ. (February 2000). "The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans". Endocrine Reviews 21 (1): 23–39.
  6. L. E. O. Crouzon. Dysostose cranio-faciale héréditaire. Bulletin de la Société des Médecins des Hôpitaux de Paris, 1912, 33: 545-555.
  7. Ignatowicz R, Gdakowicz B. Craniofacial dysostosis of the Crouzon type. Wiad Lek. Feb 15 1971;24(4):363-6.
  8. Maeda T, Hatakenaka M, Muta H, Nakayama M, Nakazaki Y, Hiroyama T, et al. Clinically mild, atypical, and aged craniofacial syndrome is diagnosed as Crouzon syndrome by identification of a point mutation in the fibroblast growth factor receptor 2 gene (FGFR2). Intern Med. May 2004;43(5):432-5.
  9. Miklaszewska M. Dysostosis cranio-facialis hederitaria. In: Miklaszewska M, Wasik F, eds. Dermatologia Pediatryczna. Vol 2. Wrocaw, Poland: Volumed; 2000:650-4.
  10. Miklaszewska M, Racawska A, Ziarkiewicz M. Syndroma Crouzon and syndromal acanthosis nigricans. Demonstration of case on the meeting of Polish Dermatological Society; February 1990.

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Last updated: 2019-07-11 21:44