Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation

World Neurosurg. 2019 Jul:127:446-450. doi: 10.1016/j.wneu.2019.04.156. Epub 2019 Apr 25.


Background: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery.

Case description: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation.

Conclusions: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.

Keywords: COL4A1; Cerebral venous thrombosis; Malignant hyperthermia; Schizencephaly; Ventriculoperitoneal shunt.

Publication types

  • Case Reports

MeSH terms

  • Collagen Type IV / genetics*
  • Dantrolene / therapeutic use
  • Fluid Therapy / methods
  • Germ-Line Mutation / genetics*
  • Humans
  • Hydrocephalus / drug therapy
  • Hydrocephalus / surgery
  • Infant
  • Male
  • Malignant Hyperthermia / etiology*
  • Muscle Relaxants, Central / therapeutic use
  • Postoperative Complications / etiology
  • Schizencephaly / genetics*
  • Sinus Thrombosis, Intracranial / drug therapy
  • Sinus Thrombosis, Intracranial / etiology*
  • Ventriculoperitoneal Shunt / adverse effects*


  • COL4A1 protein, human
  • Collagen Type IV
  • Muscle Relaxants, Central
  • Dantrolene