Sunday, March 26, 2023

Genetics of Crouzon Syndrome

Practice Essentials

Severe cases of craniosynostosis syndromes, such as Crouzon syndrome, do not present diagnostic problems. More diagnostically challenging, however, are patients with Crouzon syndrome who demonstrate mild or no dysmorphology in infancy, especially when Crouzon syndrome is absent in parents and other relatives. Therefore, abnormal head shape in infants and even slight facial dysmorphology need to be followed up.

When diagnosed, an infant needs to be referred to a craniofacial center with a track record for treating syndromic craniosynostoses. Multidisciplinary management is critical, especially because surgeries and other procedures are time sensitive. A medical geneticist should be involved through the duration of all treatments.

Crouzon syndrome is named after the French neurologist Louis Edouard Octave Crouzon (1874-1938), who had a deep interest in hereditary neurologic diseases. He described the syndrome as hereditary dysostosis craniofacialis, detailing its presence in a mother and her son, both of whom had a triad of craniofacial deformities, facial anomalies, and exophthalmos.

Crouzon syndrome belongs to a large and heterogeneous group of conditions presenting with craniosynostosis, a common symptom of which is early fusion of one or more cranial sutures. Craniosynostoses have an estimated prevalence of 1 in 2100 to 2500 live births.
The major division among craniosynostoses is between the nonsyndromic and syndromic forms. The syndromic forms, which are hereditary, make up 15-30% of all cases.
Crouzon syndrome accounts approximately for 4.8% of all cases of craniosynostosis, with the estimated birth prevalence ranging widely, from 1 in 25,000 in early studies
to 1 in 60,000 in later studies.

Inheritance of Crouzon syndrome is autosomal dominant, with complete penetrance and variable expressivity.
In about 25% of cases, a negative family history of Crouzon syndrome is observed, with the condition in these instances presumably arising from a fresh mutation.

Crouzon syndrome involves premature synostosis of coronal and sagittal sutures, starting in the first postnatal year. Once closed, the sutures have restricted growth potential. Premature fusion of skull base sutures is often seen in cases of multiple sutural synostoses, with the resulting occurrence of midfacial hypoplasia, shallow orbits, a foreshortened nasal dorsum, exophthalmos, maxillary hypoplasia, and occasional upper airway obstruction.

Unlike some other forms of autosomal dominant craniosynostosis, no digital abnormalities are present in Crouzon syndrome. See the image below.

Child with Crouzon syndrome. Note midfacial hypopl

Child with Crouzon syndrome. Note midfacial hypoplasia, proptosis secondary to shallow orbits, and ocular hypertelorism.

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