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Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.
[familial mediterranean fever]
To
evaluate
genetic
,
demographic
and
clinical
features
in
patients
with
cryopyrin-associated
periodic
syndrome
(
CAPS
)
from
the
Eurofever
Registry
,
with
a
focus
on
genotype-phenotype
correlations
and
predictive
disease
severity
markers
.
A
web-based
registry
retrospectively
collected
data
on
patients
with
CAPS
.
Experts
in
the
disease
independently
validated
all
cases
.
Patients
carrying
NLRP
3
variants
and
germline-
mutation
-negative
patients
were
included
.
136
patients
were
analysed
.
The
median
age
at
disease
onset
was
9
 
months
,
and
the
median
duration
of
follow-up
was
15
 
years
.
Skin
rash
,
musculoskeletal
involvement
and
fever
were
the
most
prevalent
features
.
Neurological
involvement
(
including
severe
complications
)
was
noted
in
40
%
and
12
%
of
the
patients
,
respectively
,
with
ophthalmological
involvement
in
71
%
,
and
neurosensory
hearing
loss
in
42
%
.
133
patients
carried
a
heterozygous
,
germline
mutation
,
and
3
patients
were
mutation
-negative
(
despite
complete
NLRP
3
gene
screening
)
.
Thirty
-
one
different
NLRP
3
mutations
were
recorded
;
7
accounted
for
78
%
of
the
patients
,
whereas
24
rare
variants
were
found
in
27
cases
.
The
latter
were
significantly
associated
with
early
disease
onset
,
neurological
complications
(
including
severe
complications
)
and
severe
musculoskeletal
involvement
.
The
T
348
M
variant
was
associated
with
early
disease
onset
,
chronic
course
and
hearing
loss
.
Neurological
involvement
was
less
strongly
associated
with
V
198
M
,
E
311
 
K
and
A
439
 
V
alleles
.
Early
onset
was
predictive
of
severe
neurological
complications
and
hearing
loss
.
Patients
carrying
rare
NLRP
3
variants
are
at
risk
of
severe
CAPS
;
onset
before
the
age
of
6
 
months
is
associated
with
more
severe
neurological
involvement
and
hearing
loss
.
These
findings
may
have
an
impact
on
treatment
decisions
.
Diseases
Validation
Diseases presenting
"musculoskeletal involvement and fever were the most prevalent features"
symptom
familial mediterranean fever
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