Keutel Syndrome

Keutel syndrome is characterised by diffuse cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenoses and facial dysmorphism.

Epidemiology

Less than 30 cases have been reported in the literature so far, with the majority of patients being diagnosed during childhood.

Clinical description

The abnormal calcification principally involves the cartilage of the ears, nose, larynx and the tracheobronchial tree. Epiphyseal stippling of the long bones and calcification of the spinal column vertebrae have also been reported. The dysmorphism is characterised by an elongated face with maxillary and midface hypoplasia (broad and depressed nasal bridge with small alae nasi). Other associated features may include hearing loss and recurrent otitis and/or sinusitis, mild intellectual deficit, frequent respiratory infections, nasal speech and, more rarely, seizures and short stature. Additional findings of white matter anomalies, encephalomalacia, optic nerve atrophy, and lax and doughy skin with prominent skin folds were reported in one affected family.

Etiology

The syndrome is caused by mutations in the gene encoding the matrix Gla protein (MGP, located at 12p13.1-p12.3).

Diagnostic methods

Diagnosis is usually suspected on the basis of the clinical presentation and radiographic examination, with abnormal cartilage calcification and brachytelephalangism being the cardinal signs of the syndrome. The diagnosis can be confirmed by mutation analysis.

Differential diagnosis

The principle differential diagnosis is X-linked recessive chondrodysplasia punctata, but abnormal calcification has also been observed in children with warfarin embryopathy (see this term) and in those with combined vitamin K-dependent coagulation factor deficiency.

Genetic counseling

The syndrome is transmitted as an autosomal recessive trait.

Management and treatment

Treatment is symptomatic and may involve angiographic dilatation for peripheral pulmonary artery stenosis and bronchodilating agents to relieve dyspnea and wheezing.

Prognosis

The prognosis for most patients is good, but life expectancy depends on the extent of the pulmonary involvement.