title: Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3.
abstract: BACKGROUND
  Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear.
  
  
  METHODS
  Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation.
  
  
  CONCLUSIONS
  Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.
authors.affiliation: Department of Pediatric Neurosurgery, Takatsuki General Hospital, 1-3-13 Kosobecho, Takatsuki City, Osaka, 569-1192, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Harada
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Miya
authors.forename: Hidetsuna
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.forename: Yonehiro
authors.initials: Y
authors.lastname: Kanemura
authors.forename: Mami
authors.initials: M
authors.lastname: Yamasaki
mesh_terms: D002196:Capillaries / Q000002:abnormalities*; D003645:Death, Sudden; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D054079:Vascular Malformations / Q000150:complications / Q000235:genetics*
chemical_list: C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt