Powell Venencie Gordon Syndrome

At a glance

A rare keratodermal syndrome where nail dystrophies are associated with axonal neuropathy and sometimes respiratory insufficiency.

Synonyms

Palmoplantar Keratoderma, Nail Dystrophy, Hereditary Motor-Sensory Neuropathy Syndrome; Axonal Neuropathy with Palmoplantar Keratoderma; Charcot-Marie-Tooth Disease, Palmoplantar Keratoderma, Nail Dystrophy Syndrome.

History

First described by J. L. Thonie in 1988.

Incidence

Very rare; fewer than 20 patients reported in three families.

Genetic inheritance

Autosomal dominant heterogeneous.

Pathophysiology

Mutations in two different genes KRT1 and MPZ on 12q.13 and 1q23 appear to be responsible for this particular association. The clinical condition is the consequence of a combination of two heterozygous mutations in different genes, and not in a common mutant one.

Diagnosis

Must be evoked by association of signs. Genetic testing is possible.

Clinical aspects

Nail dystrophy affects both toes and fingers; it can be present at birth or manifests during early childhood. Palmoplantar keratoderma becomes apparent in later childhood. Clinical (abnormal gait, hypertonia, spasticity, rigidity, paraparesis, quadriparesis) or electrophysiological evidence of axonal neuropathy with muscular atrophia are observed. Associated sensitive disturbances are hypoesthesia with stocking and glove distribution, loss of the sense of vibration and deep tendon reflexes, paresthesias, and pain. Muscle histological lesions can be present. Respiratory insufficiency can occur.

Precautions before anesthesia

Evaluate severity of the neurological and muscular lesions (clinical, electromyography, somatosensory, and motor evoked potentials). Evaluate respiratory function (chest radiograph, pulmonary function test, arterial blood gas analysis).

Anesthetic considerations

Intraoperative positioning must be careful. Pulse oximetry signal can be difficult to obtain because of nail dystrophy and its reliability has to be evaluated. Perioperative respiratory function survey if necessary.

Pharmacological implications

Muscles relaxants are not contraindicated but have to be used with caution and with a monitoring device. Succinylcholine must be avoided in case of acute exacerbation of the neurological signs (risk of hyperkaliemia). Opioids could be used with caution in spontaneously breathing patients. Regional anesthetic techniques, when applicable, might be preferable even though there are no data in this pathology.

Other conditions to be considered

• Venencie Powell Winkelmann Syndrome: In this syndrome, multiple orthopedic malformations are associated including scoliosis and brachydactyly. A particular face is observed (narrow nose, prematurely aged face).

• Fitzsimmons Syndrome: Mental retardation with spastic paraplegia and palmoplantar hyperkeratosis. The spasticity affects all four limbs (spastic paraplegia), pes cavus deformity with abnormal gait, and skin changes. Phenotype due to co-occurrence of multiple genetic mutations. No longer considered a syndrome.

References