Pena-Shokeir Syndrome Type I

At a glance

Early lethal syndrome involving multiple joint contractures, camptodactyly, facial anomalies, and pulmonary hypoplasia.

Synonyms

Fetal Akinesia/Hypokinesia Sequence; Fetal Akinesia Deformation Syndrome (FADS).

History

First described by S. D. J. Pena and W. H. K. Shokeir in 1974.

Incidence

Rare; approximately 100 cases reported. First identified in 1974. F = M.

Genetic inheritance

Autosomal recessive in more than half the cases. Etiology heterogeneous. Risk of recurrence has been estimated between 10 and 15% unless there is maternal myasthenia gravis (several cases), in which case recurrence is high. Thought to represent a lesser degree of clinical expressivity of the same mutation.

Pathophysiology

The lethal congenital contracture syndrome is caused by mutations in GLE located at 9q34, ERBB3 located at 12q13, and PIP5K1C located at 19p13. The clinical phenotype is probably caused by decreased in utero movement, whatever the cause (muscular, spinal, or cerebral). This results in ankylosis of multiple joints, absence of breathing in association with pulmonary hypoplasia, absence of swallowing resulting in polyhydramnios, and absence of facial muscle movements leading to craniofacial anomalies.

Diagnosis

Clinical based on the multiple features of disease. Approximately 30% are stillborn and those that reach term are small for dates. Antenatal ultrasonography shows lack of fetal movement and polyhydramnios. Confirmation is with muscle histology or at postmortem examination.

Clinical aspects

Neurological: muscle atrophy, generalized hypotonia, and hyporeflexia/areflexia. Musculoskeletal: arthrogryposis of multiple joints, multiple ankyloses, camptodactyly, rocker-bottom feet, short neck. Craniofacial: expressionless faces, hypertelorism, micrognathia, cleft palate. Pulmonary: hypoplasia. Cardiac: cardiac hypoplasia, arrhythmias, congenital defects. Endocrine: adrenal hypoplasia, failure to thrive. Death usually occurs in the neonatal period as a consequence of lung hypoplasia.

Precautions before anesthesia

It is unlikely that anesthesia will be required in these babies. Full assessment of the severity of the syndrome is needed. It is likely that the babies will be ventilated initially.

Anesthetic considerations

Micrognathia may make direct laryngoscopy difficult. May have significant pulmonary hypoplasia. Inhalational anesthesia and muscle relaxants appear suitable although one case with possible but poorly documented malignant hyperthermia has been published.

Pharmacological implications

Adrenal hypoplasia may require steroid supplementation.

References