Download - Typical Aicardi syndrome in a male
Typical Aicardi syndrome in a male
Aicardi syndrome (AS), identified first by
Jean Aicardi in 1965 (1), is a rare genetic
disorder characterized by infantile spasm
(IS), corpus callosal agenesis and chorio-
retinal lacunae (CRL) (2). This is an X-
linked dominant condition and occurs
almost exclusively in females because of
early embryonic lethality in hemizygous
males (3). Because of its lethality, it has
been very rarely reported in boys (4–6),
with all patients having severe motor and
speech disabilities, intractable epilepsy and
a high mortality rate (3). Although mild
cases havebeen reported (7,8), this has been
exclusively in girls. We report the first case
of AS inmale withmildmental retardation
and normal speech development.
A 21-year-old male previously thought
to have infantile epilepsy was referred
because of increasing aggressive outbursts
and suspiciousness towards family
members. On evaluation of history, he
was found to have been born of non-
consanguineous marriage, of full term at
the hospital. The prenatal period was
eventful because of the presence of
eclampsia in the mother, diagnosed in the
second trimester (untreated), and he was
delivered by emergency lower segment
caesarean section because of prolonged
labour. His weight and head circumference
were normal. The Denver developmental
screening scale (9) revealed delayed devel-
opmental milestones. Around the age of
3–4 months, seizures manifested them-
selves for the first time, mainly of a focal
nature, characterised by clustering of both
shoulder shrugging and salaamattacks and
presence of status epilepticus.Till the ageof
20 years, these continued, although with
a decreased frequency, on treatment with
60 mg phenobarbitone. At the time of
evaluation, he was found to be mildly
intellectually impaired and with normal
speech. A complete medical examination
revealed right non-paralytic squint, spastic
left-sided hemiplegia and presence of
a wide forehead with thoracolumbar ky-
phoscoliosis.His facieswasnormal.Fundal
examination revealed choroidal calcifica-
tion, otherwise was entirely normal.
He was then investigated. Radiology
revealed no evidence of costovertebral
abnormality.
Interictal electroencephalography re-
vealed intermittent alpha and diffuse theta
activity in the background. Rhythmical
slowing (delta waves) with burst suppres-
sion was noted in the right side. Magnetic
resonance imaging revealed the presence
of complete callosal agenesis. An area of
dysplasia was noted in the right frontal
lobe with colpocephaly and convergence
of lateral ventricles. He was started on
800 mg carbamazepine along with 60 mg
phenobarbitone. Risperidone 3 mg was
added to manage his suspicion and
aggressive outbursts towards his family
members. On 1-year follow-up, patient
was maintaining well on the above med-
ications, with no recurrence of seizures or
aggressive outbursts.
Discussion
AS is a sporadic disorder that affects
primarily females and is hypothesised to
be caused byheterozygousmutations in an
X-linked gene. Its main features include
a triad of ISs, agenesis of the corpus
callosum and distinctive CRL. Additional
common findings include moderate to
profound mental retardation, grey matter
heterotopia, gyral anomalies and verte-
bral and rib defects. Most patients have
severe learning disability, intractable epi-
lepsy, agenesis of the corpus callosum and
reduced life expectancy (3).
Being a differential diagnosis of ISs, it
has been usually reported in infants and
children, with the exception of one case
(8). Our case is only the second such report
in adulthood and the first in a male,
showing that a milder form of AS exists
and that there may be a wide spectrum of
AS than has been described before (10–12).
He is only mildly mentally disabled, and
his epilepsy has been well controlled.
However, he does not have the typical
CRLpresent from childhood, but agenesis
of the corpus callosum along with other
biological markers of frontal dysplasia
and colpocephaly supports the diagnosis
of AS. The striking feature is that he has
adjusted well to his family till the age of
21 years, providing further evidence that
a mild form of the disease does exist. The
presenting complaint of increased aggres-
sion and suspicion in this patient could,
however, be linked to right hemispheric
dysfunction caused by epilepsy, hypothe-
sized to cause paranoid psychoses and
Capgras syndrome (13).
Even though complete agenesis has
been linked to severe mental retardation
(8), our case shows otherwise, suggesting
that there is no relation between the two.
His mental disability may be linked to
hormonal deficiency during neurogenesis,
also seen in mental retardation accompa-
nying hypopituitarism (14). Furthermore,
most of these cases have been described to
have intractable epilepsy; overall outlook
need not necessarily be gloomy keeping in
view several cases that have shown com-
plete remission (8,10) including ours. As
efforts to map a genetic locus have been
unsuccessful so far, an absolutely firm
diagnosis will have to await the discovery
of a genetic marker. Until such time,
biological markers may have to suffice,
with hope from functional magnetic reso-
nance imaging being able to further map
out dysfunctional cortical areas (15).
Sahoo Saddichha,Narayana Manjunatha,
Sayeed Akhtar
Central Institute of Psychiatry, Kanke, Ranchi,India, 834006.
326
Sahoo Saddichha,Central Institute of Psychiatry,
Kanke, Ranchi,834006, India.
Tel: 191 98353 69975;Fax: 191 65122 33668;
E-mail: [email protected]
Acta Neuropsychiatrica 2007: 19:326–327
� 2007 The Authors
Journal compilation � 2007 Blackwell
Munksgaard
DOI: 10.1111/j.1601-5215.2007.00237.x
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COMMENT & CRITIQUE
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