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: saddichha@gmail.com

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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