Keutel syndrome

Overview

Keutel syndrome is a rare inherited disorder characterized by abnormal cartilage calcification, distinctive facial features, brachytelephalangy (shortened finger bones), and respiratory tract anomalies. First described in 1971, this autosomal recessive condition typically presents in early childhood. The syndrome primarily affects the skeletal and respiratory systems, and although it is non-progressive, it can cause significant morbidity due to airway complications and recurrent respiratory infections.

Causes

Keutel syndrome is caused by mutations in the MGP gene (matrix Gla protein), which plays a crucial role in preventing abnormal calcification in soft tissues, particularly cartilage and blood vessels. The MGP protein is vitamin K-dependent and normally inhibits inappropriate mineralization. Mutations in this gene result in loss of function, leading to abnormal calcification of cartilage and other soft tissues. The condition is inherited in an autosomal recessive pattern, meaning both copies of the gene must be mutated for the disorder to manifest.

Symptoms

Clinical features of Keutel syndrome vary in severity but often include:

• Abnormal cartilage calcification: Especially in the trachea, leading to airway stiffness and respiratory problems

• Brachytelephalangy: Shortening of the distal phalanges (fingertips)

• Facial dysmorphism: Midface hypoplasia, depressed nasal bridge, and small jaw

• Hearing loss: Often conductive, due to calcification of the auditory canal structures

• Recurrent respiratory infections: Due to narrowed and rigid airways

• Tracheobronchial calcifications visible on X-ray

• Possible mild intellectual disability in some cases

Symptoms usually develop in infancy or early childhood and tend to remain stable throughout life.

Diagnosis

Diagnosis of Keutel syndrome is based on clinical examination, imaging studies, and genetic testing. Key diagnostic steps include:

• Physical examination revealing characteristic facial features and shortened fingertips

• X-rays or CT scans showing calcification of cartilage in the trachea, ears, or ribs

• Hand radiographs confirming brachytelephalangy

• Audiometric tests to assess hearing loss

• Genetic testing to identify mutations in the MGP gene

Given the overlap of symptoms with other skeletal dysplasias, genetic confirmation is essential for accurate diagnosis.

Treatment

There is no cure for Keutel syndrome, and treatment is supportive and focused on managing symptoms and preventing complications. Management may include:

• Respiratory care: Monitoring and treating airway obstruction and infections; in severe cases, surgical intervention or tracheostomy may be required

• Hearing support: Use of hearing aids for conductive hearing loss

• Physical therapy: To improve mobility and function, particularly in the hands

• Speech therapy: If speech is affected due to hearing loss or facial structure

• Regular follow-up with a multidisciplinary team including pulmonologists, ENT specialists, and genetic counselors

Prognosis

The prognosis for individuals with Keutel syndrome is generally favorable, as the condition is non-progressive. While respiratory complications and hearing loss can affect quality of life, early diagnosis and appropriate supportive care can help manage these issues effectively. Most individuals can live into adulthood, although they may require ongoing medical support for respiratory and hearing-related problems. Lifespan is typically normal if serious complications are avoided.