Crouzonodermoskeletal syndrome

Overview

Crouzonodermoskeletal syndrome is a rare genetic condition that combines features of Crouzon syndrome with additional skin and skeletal abnormalities. It is also referred to as Crouzon syndrome with acanthosis nigricans. The condition is characterized by craniosynostosis (premature fusion of skull bones), distinct facial deformities, thickened and hyperpigmented skin (especially around body folds), and skeletal anomalies. It differs from classical Crouzon syndrome in both severity and the involvement of other organ systems, particularly the skin.

Causes

Crouzonodermoskeletal syndrome is caused by a specific mutation in the FGFR3 gene (fibroblast growth factor receptor 3), most commonly the Ala391Glu (A391E) substitution. This gene plays a crucial role in bone growth and skin development. The condition is inherited in an autosomal dominant pattern, meaning one copy of the mutated gene is sufficient to cause the disorder. However, most cases result from new (de novo) mutations with no prior family history.

Symptoms

The syndrome includes features of Crouzon syndrome along with additional dermatologic and skeletal manifestations. Common symptoms include:

• Craniosynostosis: Premature fusion of skull sutures leading to abnormal head shape

• Midface hypoplasia: Underdeveloped midfacial region causing breathing difficulties and dental issues

• Proptosis: Bulging eyes due to shallow orbits

• Acanthosis nigricans: Thickened, darkened, velvety skin in body folds such as the neck, armpits, and groin

• Skin papillomas: Wart-like skin growths

• Skeletal anomalies: Including vertebral abnormalities and short stature in some cases

• Dental crowding and malocclusion

• Normal limbs: Unlike in some other craniosynostosis syndromes, the hands and feet are usually not affected

Diagnosis

Diagnosis is based on clinical findings, imaging studies, and genetic testing. The distinguishing combination of craniosynostosis with skin changes often points toward this specific subtype. Diagnostic steps include:

• Physical examination: Identification of craniofacial deformities and skin abnormalities

• CT or MRI scans: To assess skull fusion and brain structures

• Genetic testing: To confirm a mutation in the FGFR3 gene (specifically A391E)

• Dermatologic evaluation: To characterize skin thickening and pigmentation

• Ophthalmologic and audiologic tests: To check for vision and hearing complications

Treatment

Treatment for Crouzonodermoskeletal syndrome is multidisciplinary and focuses on managing craniofacial abnormalities, skin lesions, and potential complications. Common treatments include:

• Cranial surgery: To relieve intracranial pressure and allow normal brain development

• Midface advancement: For improving breathing, dental alignment, and facial symmetry

• Dermatologic care: Topical or systemic treatments for acanthosis nigricans, such as retinoids or keratolytic agents

• Orthodontic intervention: To correct dental malalignment

• Monitoring and managing complications: Such as hydrocephalus, hearing loss, or vision problems

• Supportive therapies: Speech therapy, occupational therapy, and developmental assessments

Prognosis

The prognosis for individuals with Crouzonodermoskeletal syndrome depends on the severity of the cranial and facial abnormalities and how early interventions are provided. With timely craniofacial surgery and supportive care, many children can achieve improved appearance, function, and quality of life. Intellectual development is typically normal, although complications from raised intracranial pressure or visual/hearing impairments can affect learning. Lifelong dermatologic and medical follow-up is recommended.