Unexpected mental illnesses found in a spectrum of a rare genetic
disorder
Researchers recommend screening to better identify treatment options


Date:
June 25, 2020
Source:
University of California - Davis Health
Summary:
Researchers found an unexpected spectrum of mental illnesses in
patients with a rare gene mutation. These patients had a ''double
hit'' condition that combined features and symptoms of fragile
X syndrome and premutation disorder, in addition to a range of
psychiatric symptoms. The findings revealed the need for clinicians
to consider the complexities of the co- existing conditions of
patients with both psychological and fragile X associated disorders.



FULL STORY ==========================================================================
UC Davis MIND Institute researchers found an unexpected set of mental
illnesses in patients with a spectrum of a rare genetic disorder. Their
study revealed the need for clinicians to consider the complexities of co-existing conditions in patients with both psychological and fragile
X associated disorders.


========================================================================== Double-hit fragile X spectrum cases The patients had a "double-hit"
condition that combined features and symptoms of fragile X syndrome and premutation disorder.

Fragile X syndrome (FXS), a rare single-gene disorder, is the leading
inherited cause of intellectual disability. It is caused by a lack of
the fragile X mental retardation protein (FMRP) resulting from a change,
called mutation, in the FMR1 gene.

In most people, the CGG section of the FMR1 gene is repeated between 10
to 40 times. In some rare cases, individuals have premutation disorder
when their FMR1 gene has 55 to 200 CGG repeats. When this section expands
to over 200 repeats, there is a full mutation in the gene. This full
mutation causes an inability to produce FMRP and leads to FXS.

The study presented 14 cases of male patients with FMR1-gene mutations
and a variety of psychiatric disorders. These patients, ages ranging
between nine and 58 years, had features resembling FXS and symptoms
common among premutation carriers.



==========================================================================
FXS symptoms include hand flapping, hyperactivity, recurrent ear
infections, severe anxiety and tantrums. Individuals with FXS frequently
have speech and language delays, behavior challenges and symptoms of
autism spectrum disorder (ASD).

Premutation, on the other hand, is associated with the development
of neurological problems associated with aging. One example of such
age-related problems is Fragile X-associated tremor ataxia syndrome
(FXTAS). FXTAS is a disease characterized by progressively severe tremor
and difficulty with walking and balance. Premutation is also associated
with medical and psychiatric problems such as migraines, hypertension,
sleep apnea, restless legs syndrome, anxiety and depression.

Neurological and developmental problems The study found that patients
with premutation had a much earlier onset of neurological problems. Some
even had earlier symptoms of neurodegeneration, particularly if they
had developmental delay or ASD during their childhood.

They also showed trouble with their emotional processing.

"Lower levels of FMRP can cause a range of emotional processing issues,"
said Andrea Schneider, associate research scientist in the Department
of Pediatrics and at UC Davis MIND Institute and the lead author on the
study. "Some of the common emotion-related disorders we found are mood disorders, anxiety and psychotic features." The researchers called for
more studies on the association of psychosis and lower FMRP levels -- especially in patients with a double hit condition. The case series
also highlighted the need for clinicians to consider additional possible diagnosis for FMR1 mutations in psychiatric patients.

"Clinicians need to be aware of the physical and mental toll on patients
with a FMR1 mutation who also show symptoms of psychosis or early onset
of neurological problems," said Paul Hagerman, professor of biochemistry
and molecular medicine at UC Davis and co-author on the study. "This understanding helps develop treatment plans that address the multiple
needs of these patients."

========================================================================== Story Source: Materials provided by
University_of_California_-_Davis_Health. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Andrea Schneider, Tri Indah Winarni, Ana Mari'a Cabal-Herrera, Susan
Bacalman, Louise Gane, Paul Hagerman, Flora Tassone, Randi Hagerman.

Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for
psychiatric features in men with FMR1 premutations. Translational
Psychiatry, 2020; 10 (1) DOI: 10.1038/s41398-020-00863-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200625102538.htm

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