Keutel Syndrome

Polymalformative syndrome characterized by characteristic facies, brachytelephalangism, calcification of the cartilage, deafness, and pulmonary stenosis.

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

(NB: Another Keutel syndrome (termed Keutel syndrome II) is characterized by humeroradial synostosis transmitted as an autosomal recessive trait.)

Approximately 21 cases have been reported to date.

Autosomal recessive inheritance. Gene map locus is short arm of chromosome 12 (12p13.1-p12.3). Consanguineous parents are common.

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

Clinical diagnosis.

Macro-, normo-, and microcephaly have been described in these patients. A depressed nasal bridge, often combined with midface and maxillary hypoplasia are typical. Sensorineural hearing loss, optic nerve atrophy, and mental delay may 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 reported.

Identify which sites or organs are affected by abnormal calcifications. Evaluate for pulmonary hypertension and/or cor pulmonale caused by chronic airway obstruction and/or pulmonary artery stenosis. Electrocardiogram and echocardiogram should be considered prior to anesthesia. Right heart and pulmonary angiograms may be required to diagnose peripheral pulmonary artery stenosis. Voice changes or stridor may indicate calcification of laryngeal cartilage and/or epiglottis. Theoretically, calcification of the costochondral joints could lead to a restrictive-type pulmonary disease if chest expansion is limited. Arterial blood gases, chest radiography, and pulmonary function tests are indicated if sufficient suspicion exists. Check renal function because of possible calcifications and hydronephrosis. Type of seizure activity, current management, and degree of control should be evaluated. Deaf patients may be more anxious and difficult to communicate with. Sedative premedication and/or the presence of the primary caregiver (sign language) for induction of anesthesia may be helpful.

Midfacial hypoplasia may render airway management, especially placement of a nasal endotracheal tube, difficult. These patients may require airway support postoperatively if prone to obstruction. A smaller endotracheal tube than expected may be required if the glottis or trachea is stenotic. May be more prone to postoperative laryngeal edema. If laryngeal function is compromised, patients should be extubated awake so that protective airway reflexes are intact. If pulmonary hypertension is present, avoid increased pulmonary vascular resistance (aim for mild alkalosis and hypocapnia and avoid hypoxia and high airway pressures) or depressed right ventricular function. If respiratory function is compromised because of restricted chest wall expansion, postoperative respiratory support in an intensive care unit may be required.

Some antiseizure medications, such as phenytoin, can inhibit nondepolarizing muscle relaxant function. Phenobarbital up-regulates liver enzymes and may cause increased hepatic clearance of anesthetic agents. Doses should be titrated to desired effect.

Binder Syndrome (Maxillonasal Dysplasia Syndrome): Mild form of chondrodysplasia punctata with maxillonasal dysplasia and teeth malocclusion that may be an allelic variant of Keutel syndrome.