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Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3

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Abstract

Introduction

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.

Case report

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.

Conclusion

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.

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Acknowledgments

We appreciate the support from the Health Sciences Research Grants for Research of Intractable Disease (2010-ID-131 to YM) and the Research on Applying Health Technology (H23-013 to FM, MK, KK, YK, and MY) from the Ministry of Health, Labor, and Welfare of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatric Neurosurgery, Takatsuki General Hospital, 1-3-13 Kosobecho, Takatsuki City, Osaka, 569-1192, Japan

    Atsuko Harada, Takumi Yamanaka & Mami Yamasaki

  2. Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Fuyuki Miya & Tatsuhiko Tsunoda

  3. Department of Radiological Science, International University of Health and Welfare, Graduate School, Fukuoka, Japan

    Hidetsuna Utsunomiya

  4. Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan

    Mitsuhiro Kato

  5. Center for Medical Genetics, School of Medicine, Keio University, Tokyo, Japan

    Kenjiro Kosaki

  6. Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan

    Yonehiro Kanemura & Mami Yamasaki

  7. Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan

    Yonehiro Kanemura

Authors
  1. Atsuko Harada
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  2. Fuyuki Miya
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Correspondence to Mami Yamasaki.

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Harada, A., Miya, F., Utsunomiya, H. et al. Sudden death in a case of megalencephaly capillary malformation associated with a de novo mutation in AKT3 . Childs Nerv Syst 31, 465–471 (2015). https://doi.org/10.1007/s00381-014-2589-y

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  • DOI: https://doi.org/10.1007/s00381-014-2589-y

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