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At a glance

It is a polymalformative syndrome presenting characteristic hypoplasia of the mid-face, micrognathia, brachytelephalangism, calcifications of the cartilage, deafness, and tracheobronchial and peripheral pulmonary stenosis.

Synonyms

Keutel Syndrome I; Pulmonic Stenosis, Brachytelephalangism, and Calcification of Cartilages.

N.B.: Another Keutel Syndrome [termed Keutel Syndrome II] is characterized by humeroradial synostosis transmitted as an autosomal recessive trait.

History

It was first identified in 1972 by J. Keutel et al, as a novel rare genetic disorder sharing similar symptoms with chondrodysplasia punctata.

Incidence

Approximately 21 cases have been reported to date.

Genetic inheritance

Autosomal recessive inheritance. It is associated with abnormalities in the gene coding for matrix gla protein (MGP). Gene map locus is short arm of chromosome 12 (12p13.1-p12.3). Consanguineous parents are often associated as they may both carry the defect.

Pathophysiology

Phenotype related to faulty encoding of the human matrix Gla protein (MGP), which plays an important role in regulation of extracellular matrix calcification.

Diagnosis

The initial diagnosis relies upon the presence of hypoplasia of the midface, micrognathia, nasal bridge depression, and wide mouth with dental malocclusion. The use of electroencephalography, computed tomography (CT) scanning, and conventional x-ray will contribute to the diagnosis in demonstrating the diffuse cartilage calcification and brachytelephalangism. The presence of tracheobronchial and peripheral pulmonary arterial stenosis will rely on the same radiological and ultrasonographic techniques. Hearing loss, facial dysmorphism, and mental retardation are confirmed with clinical history and evaluation.

Clinical aspects

Macro-, normo-, and microcephaly have been described in these patients. A depressed nasal bridge, often combined with midface and maxillary hypoplasia, is characteristic of this medical condition. Sensorineural hearing loss, optic nerve atrophy, and mental delay may also be present. Electroencephalography may document a diffuse cerebral disturbance with epileptiform discharges, and scattered punctate foci of calcification in the subcortical white matter and cortex have been demonstrated. Calcification of cartilage may affect the ears, nose, epiglottis, larynx, trachea (see below), and ribs. Stippled epiphyses, which represent calcifications of the knees and elbows, may occur as early signs of the disease. Brachytelephalangism (short terminal phalanges) with short nails results in a drumstick-like shape of the fingers, which is often combined with mild-to-moderate distal interphalangeal stiffness. Most of these patients have cardiac issues, typically increased right ventricular pressures and pulmonary artery hypertension either due to pulmonary (valvular or supravalvular) stenosis or cor pulmonale as a consequence of calcification of tracheal, paratracheal, bronchial, and rib cartilages. These calcifications may lead to significant obstruction of the tracheobronchial tree down to the level of the lobular bronchi. Renal calcifications and bilateral hydronephrosis as a result of narrowing of the urethrovesicular junction or bladder outlet obstruction with vesicoureteral reflux have also been ...

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