X-Linked Lissencephaly with Absent Corpus Callosum and Ambiguous Genitalia: A Case Report

Document Type: Case Report

Authors

1 Assistant Professor, School of Medical Sciences, Alborz University of Medical Sciences, Karaj, Iran

2 Professor, School of Medical Sciences, Babol University of Medical Sciences, Babol, Iran

3 Associate Professor, School of Medical Sciences, Babol University of Medical Sciences, Babol, Iran

Abstract

Background: X-linked lissencephaly with ambiguous genitalia (XLAG) is a recently described genetic disorder, in which patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly, and male genotype with ambiguous genitalia. XLAG is responsible for a severe neurological disorder of neonatal onset in boys. A gyration defect consisting of anterior pachygyria and posterior agyria with a moderately thickened brain cortex, dysplastic basal ganglia, and complete agenesis of the corpus callosum are consistently found on magnetic resonance imaging (MRI). Females related to affected boys may have epilepsy and mental retardation or display agenesis of corpus collosum on MRI. These findings can indicate an X-linked semi-dominant inheritance.
Case presentation: The patient was a one-day-old term neonate admitted to our neonatal intensive care unit due to refractory seizure. He was the second child of the family, born to non-consanguineous and healthy parents. His midface was slightly hypoplastic with long and smooth philtrum; the neonate had ambiguous genitalia, as well. Hormonal investigation demonstrated elevated serum 17OH-progesterone, dehydroepiandrosterone sulfate, and testosterone levels. Chromosomal analysis showed a normal male karyotype (46, XY). Brain computed tomography scan showed a typical pattern of lissencephaly with a posterior-to-anterior gradient of severity consisting of frontal pachygyria, posterior agyria, and absence of corpus collosum

Keywords


  1. Dobyns WB, Truwit CL. Lissencephaly and other malformations of cortical development: 1995 update. Neuropediatrics. 1995; 26(3):132-47.
  2. Berry‐Kravis E, Israel J. X‐linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus. Ann Neurol. 1994; 36(2):229-33.
  3. Bonneau D, Toutain A, Laquerrière A, Marret S, Saugier‐Veber P, Barthez MA, et al. X‐linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol. 2002; 51(3):340-9.
  4. Pilz DT, Matsumoto N, Minnerath S, Mills P, Gleeson JG, Allen KM, et al. LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet. 1998; 7(13):2029-37.
  5. Dobyns WB, Berry‐Kravis E, Havernick NJ, Holden KR, Viskochil D. X‐linked lissencephaly with absent corpus callosum and ambiguous genitalia. Am J Med Genet. 1999; 86(4):331-7.
  6. Ogata T, Matsuo N, Hiraoka N, Hata JI. X‐linked lissencephaly with ambiguous genitalia: Delineation of further case. Am J Med Genet. 2000; 94(2):174-6.
  7. Uyanik G, Aigner L, Martin P, Groβ C, Neumann D, Marschner-Schäfer H, et al. ARX mutations in X-linked lissencephaly with abnormal genitalia. Neurology. 2003; 61(2):232-5.
  8. Spinosa MJ, Liberalesso PB, Vieira SC, Olmos AS, Löhr A Jr. Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG syndrome. Arq Neuropsiquiatr. 2006; 64(4):1023-6.
  9. Friede RL. Perinatal lesions of white matter. Berlin: Developmental Neuropathology Springer-Verlag; 1991. P. 69-81.
10. Berg MJ, Schifitto G, Powers JM, Martinez-Capolino C, Fong CT, Myers GJ, et al. X-linked female band heterotopia-male lissencephaly syndrome. Neurology. 1998; 50(4):1143-6.

  1. Dobyns WB, Truwit CL. Lissencephaly and other malformations of cortical development: 1995 update. Neuropediatrics. 1995; 26(3):132-47.
  2. Berry‐Kravis E, Israel J. X‐linked pachygyria and agenesis of the corpus callosum: evidence for an X chromosome lissencephaly locus. Ann Neurol. 1994; 36(2):229-33.
  3. Bonneau D, Toutain A, Laquerrière A, Marret S, Saugier‐Veber P, Barthez MA, et al. X‐linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol. 2002; 51(3):340-9.
  4. Pilz DT, Matsumoto N, Minnerath S, Mills P, Gleeson JG, Allen KM, et al. LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet. 1998; 7(13):2029-37.
  5. Dobyns WB, Berry‐Kravis E, Havernick NJ, Holden KR, Viskochil D. X‐linked lissencephaly with absent corpus callosum and ambiguous genitalia. Am J Med Genet. 1999; 86(4):331-7.
  6. Ogata T, Matsuo N, Hiraoka N, Hata JI. X‐linked lissencephaly with ambiguous genitalia: Delineation of further case. Am J Med Genet. 2000; 94(2):174-6.
  7. Uyanik G, Aigner L, Martin P, Groβ C, Neumann D, Marschner-Schäfer H, et al. ARX mutations in X-linked lissencephaly with abnormal genitalia. Neurology. 2003; 61(2):232-5.
  8. Spinosa MJ, Liberalesso PB, Vieira SC, Olmos AS, Löhr A Jr. Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG syndrome. Arq Neuropsiquiatr. 2006; 64(4):1023-6.
  9. Friede RL. Perinatal lesions of white matter. Berlin: Developmental Neuropathology Springer-Verlag; 1991. P. 69-81.
10. Berg MJ, Schifitto G, Powers JM, Martinez-Capolino C, Fong CT, Myers GJ, et al. X-linked female band heterotopia-male lissencephaly syndrome. Neurology. 1998; 50(4):1143-6.