Polymalformative syndrome characterized by
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.
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.