Secondary Schizophrenia (132 page)

brain and are good candidates theoretically for brain
PWS is associated with a much-increased rate of psy-dysfunction, but this is mostly evidenced by epilepsy,
chotic disorder, which presents as an intermittent
which is not associated with PWS and furthermore the
schizo-affective disorder. When all reports of psy-GABA genes are not imprinted.

chosis in PWS are considered, maternal uniparental
Of the many genes outside the critical region,
disomy appears to increase the risk of psychosis by
none is currently known to be maternally imprinted,
five to six times compared with the deletion form. The
and none has been conclusively linked to psychosis.

mechanism of such increased risk is as yet unknown.

It has been a suggestion that a gene is associated
However, studies to investigate this are indicated not
with growth on chromosome 15 outside the q(11–13)
just for their relevance to PWS, but because of their
region because patients with Angelman Syndrome due
potential to elucidate the pathogenesis of psychosis in
to UPD have enhanced growth compared to those with
general.

deletion; but here, the UPD is paternal. Another difficulty is that UPD may uncover the effect of an autoso-

Acknowledgments

mal recessive gene, as found in a child with Bloom Syndrome (BS), and PWS, where the mother was a carrier
The Australian Child to Adult Development Study
of BS (localized to 15(q25–26))
[25].

was supported by the National Health and Medical
The genetic component to the psychosis in PWS is
Research Council grant number 113844. Part of this
unclear and why maternal UPD of 15(q11–13) should
work was carried out while Stewart Einfeld and Sophie
predispose to psychosis is unresolved. Recent stud-Kavanagh were at the School of Psychiatry, University
ies suggest that epigenetic factors on chromosome 18

of New South Wales.

may play an etiopathological role in schizophrenia
Thanks to Siân Horstead for editing assistance.

330

Chapter 25 – Psychosis in Prader-Willi Syndrome

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331

Section 3

Organic syndromes of schizophrenia: genetic disorders related to SLP

26Friedreich’sAtaxiaandschizophrenia-like

psychosis

Perminder S. Sachdev

Facts box

Clinical features

r
Friedreich’s Ataxia (FRDA) is an autosomal
Age of onset

recessive neurodegenerative disorder that is

the most common cause of inherited ataxia.

The typical onset is in the first two decades of life.

It is caused by triplet GAA expansion on

The Quebec Cooperative Study criteria
[3]
suggested
chromosome 9q13.

that the onset must be before age 20 years. The Hard-r
ing
[2]
criteria extended the upper limit to 25 years.

It is characterized by onset at the age 5–25

In the large Dürr and colleagues
[4]
series, the mean
years, with neurological features (progressive
age of onset was 15.5
±
8 years, with 19/140 (13.6%)
gait and limb ataxia; dysarthria; areflexia,

having an age of onset after 25 years, which is gen-loss of vibration, and proprioceptive sense;
erally regarded as late-onset. The number of repeats
abnormal eye movements; pyramidal

on the abnormal gene relates to the age of onset (dis-weakness of feet and cognitive dysfunction);
cussed later), and late onset is associated with an atyp-cardiomyopathy; diabetes; scoliosis; and pes
ical presentation. The discovery of the FRDA gene has
cavus.

r

extended the range of ages of onset from 2 to 51 years
It is associated with cognitive dysfunction

[4].

and intellectual impairment in a minority,

personality disturbance, and depression.

r

Signs and symptoms

Cases of schizophrenia-like psychosis with

paranoid delusions and hallucinations have

Neurological features

been reported that respond to antipsychotic

FRDA primarily involves the ascending and descend-drugs. The reports are too few to determine
ing tracts of the spinal cord, in particular the
prevalence or establish a specific relationship
spinocerebellar tracts, the pyramidal tracts, and pos-between FRDA and schizophrenia.

terior columns. This, combined with involvement of
the cerebellum, peripheral nerves, dorsal roots of the
spinal cord and the tracts and nuclei of the lower brain
stem (including the optic nerve), explains the diverse
neurological features. The frequency of the clinical fea-FRDA is an autosomal recessive neurodegenerative
tures in two series is summarized in
Table 26.1.

disorder that is the most common cause of inher-In almost all cases, the initial symptom is gait
ited ataxia. Nicholaus Friedreich first described it in
ataxia, although in a few cases, scoliosis may be
a series of papers in 1863–1877
[1]
, but it is only
present before ataxia becomes manifest. Ataxia was
recently, since the discovery of the underlying genetic
present in all patients in the Dürr and colleagues
abnormality, that its full spectrum is becoming clear.

[4]
series. This may appear as clumsiness in the
Its symptoms relate to the central nervous system,
early stages, but the ataxia gradually worsens, with
heart, and pancreas. Its prevalence is estimated at
the development of a broad-based and lurching gait,
about 1 in 50,000 individuals in European populations
and spreads to the arms, leading to action tremor.

[2].

Cervical involvement leads to titubation and, in the
332

Chapter 26 – Friedreich’s Ataxia and schizophrenia-like psychosis

Table 26.1
Signs and symptoms of FRDA: data from two large
later stages, truncal involvement may make even sit-studies. Patients in the D ürr
et al.
study were all homozygous for
ting difficult.