Psychotic symptoms, epilepsy, mental retardation, and brain malformation in a patient with 45,XO/46,XX mosaicism: Detection of mutation of ARX molecule


Koji Fukuda, MD, PhD, Department of Psychiatry, Minamichita Hospital, 86 Toyooka-Magohazam Minamichita Chita, Aichi 470-4311, Japan. Email:

45,XO/46,XX mosaicism is associated with Turner syndrome and is rarely associated with serious abnormalities of brain structure or malformation of cortical development.1,2 In addition, individuals with Turner syndrome are reported to display less mental illness.3,4 We report herein a case of 45,XO/46′XX mosaicism without typical Turner syndrome symptoms but with psychotic symptoms, epilepsy, mental retardation, and brain malformation resembling lissencephaly.

Ms A is a 63-year-old woman with a history of intractable epilepsy, psychotic symptoms, and mental retardation. She had her first seizure at the age of 10. From the age of 14 years onwards, she had repeated complex partial seizures. At the age of 20, she experienced her first psychotic symptoms. She was hospitalized 11 times because of her refractory psychotic symptoms and repeated seizures, and responded poorly to antipsychotic and anticonvulsant medication. She had a normal reproductive lifespan and delivered a daughter. During the latest admission, magnetic resonance imaging of the brain revealed noticeable frontal and temporal lobe atrophy and an asymmetric irregular gyral pattern. An absence of gyri, which is suggestive of lissencephaly, was noted dominantly in the left frontal and temporal lobe. Several interictal electroencephalogram recordings showed spikes localized on the bilateral fronto-temporal region, especially F3 and T5. Peripheral blood cells were analyzed using standardized cytogenetic methods. Of 30 peripheral blood mononuclear cells examined, eight were of the karyotype 45,XO and 22 were 46XX.

We hypothesize that this chromosomal abnormality could explain the brain abnormality. Early this year, X chromosome-linked, aristaless-related, homeobox gene (ARX) was found to be associated with X-linked mental retardation, epilepsy and lissencephaly.5 We then investigated a mutation of ARX molecule in the present case. Mutation of ARX, however, was not detected in the present patient. For analysis of ARX, we obtained written informed consent. This study was approved by the Ethical Cornmittee of Shizuoka Prefectural Mental Care ard Rehabilitation Center.

There have been very few reports that mention the relationship between Turner syndrome and psychiatric symptoms.4 Two reports have mentioned a case resembling the present one.1,2 Both of those patients had epilepsy, mental retardation, and lissencephaly. Neither of those patients, however, was reported to present psychotic symptoms. Further cases resembling the present one should provide insight into these types of patients.