Download Albinism genetics types and phenotypes appearance

The Spectrum of Albinism
Ophthalmological,
Ophthalmological, nystagmographic
nystagmographic and
and fMRI-Evaluation
fMRI-Evaluation
NOAH
Department
Departmentof
ofOphthalmology
Ophthalmology
Barbara
Barbara Käsmann
Käsmann*
*
Paediatric
Paediatric Ophthalmology
Ophthalmology and
and Paediatric
Paediatric Low
Low Vision
Vision
Head:
Head: PD
PD Dr.
Dr. Barbara
Barbara Käsmann
Käsmann MD
MD
Department
Department of
of Ophthalmology
Ophthalmology
Chairman:
Prof.
Dr.
Chairman: Prof. Dr. K.W.
K.W. Ruprecht
Ruprecht
University
University of
of Saarland
Saarland
DD 66421
66421 Homburg
Homburg (Saar)
(Saar)
*Ophthalmological
*Ophthalmological Consultant
Consultant for
for NOAH
NOAH Germany
Germany
National
National Organisation
Organisation for
for Albinism
Albinism and
and Hypopigmentation
Hypopigmentation
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
University Campus and Medical School,
University of Saarland
Germany
Saarland:
Saarland: Geographical
Geographical center
center of
of Europe
Europe
Adjacent
Adjacent to:
to:
-- France
France
-- Luxembourg
Luxembourg
-- Belgium
Belgium
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and genetics
genetics
•• Oculocutaneous
Oculocutaneous albinism
albinism
•• Ocular
Ocular albinism
albinism
•• Syndromes
Syndromes with
with oculocutaneous
oculocutaneous albinism
albinism
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and genetics
genetics
••Oculocutaneous
Oculocutaneous albinism
albinism
••Ocular
Ocular albinism
albinism
••Syndromes
Syndromes with
with oculocutaneous
oculocutaneous
albinism
albinism
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and genetics
genetics
•• Oculocutaneous
Oculocutaneous albinism
albinism
•• Ocular
Ocular albinism
albinism
•• Syndromes
Syndromes with
with oculocutaneous
oculocutaneous albinism
albinism
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and genetics
genetics
••Oculocutaneous
Oculocutaneous albinism
albinism
••Ocular
Ocular albinism
albinism
••Syndromes
Syndromes with
with oculocutaneous
oculocutaneous albinism
albinism
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Moleculargenetic Analysis
As far as known up to now (May 2003)
There are 11 genes whose alterations can be associated with albinism
Type
Type of
of Albinism
Albinism
Chromosome
Chromosome // Gene
Gene
Oculocutaneous
Oculocutaneous Albinism
Albinism
•• OCA1
11
OCA1
11 // TYR
TYR
•• OCA2
15
OCA2
15 // PP
•• OCA3
99 // TRP1
OCA3 (described
(described only
only in
in Africans)
Africans)
TRP1
•• OCA4
55 // MATP
OCA4 (Lit.:
(Lit.: one
one pt.,
pt., own
own study:
study: 44 patients)
patients)
MATP
•• Syndromes
Syndromes associated
associated with
with OCA
OCA
––
––
––
HPS
HPS (1
(1 –– 4)
4)
CHS
CHS
OCA
OCA not
not in
in all
all cases:
cases:
––
––
3,5,10,22
3,5,10,22
11 // CHS
CHS
15
15 // PP
Prader
Prader Willi
Willi Syndrom
Syndrom
Angelman
Angelman Syndrom
Syndrom
Okular
Okular Albinism
Albinism
•• OA1
OA1 (Nettleship-Falls)
(Nettleship-Falls)
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
XX (OA1)
(OA1)
Types of Albinism
N
N=
= 286
286 Persons
Persons with
with Albinism
Albinism
Type of Albinism
9,93%
n=28
3,19%
n=9
25,53%
n=72
OCA1
OCA2
OA
Syndrome
unclear
17,38%
n=49
Unclear,
Unclear, nn =
= 28
28
43,97%
n=124
** Phaenotypically
Phaenotypically not
not conclusive
conclusive
** Moleculargenetic
Moleculargenetic analysis
analysis
Syndromes:
not
not yet
yet finished
finished
-PWS
-HPS
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Age
Age Distribution
Distribution in
in our
our Albinism
Albinism Patients
Patients
Department
Department of
of Paediatric
Paediatric Ophthalmology!
Ophthalmology!
Age Distribution
N = 286 Patients with Albinism
70
Number of Patients
60
50
Number of Children
due to Author being
Medical Advisor
to NOAH Germany
NOAH
NOAH
40
National
National
Organisation
Organisation of
of
Albinism
Albinism and
and
Hypopigmentation
Hypopigmentation
30
20
10
0
5,00
15,00
25,00
35,00
45,00
55,00
65,00
75,00
10,00
20,00
30,00
40,00
50,00
60,00
70,00
Age (years)
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Significant
Significant Differences
Differences in
in Phaenotype
Phaenotype and
and
Ocular
Ocular Findings
Findings
•• All
All types
types of
of albinism
albinism show
show aa high
high variability
variability of:
of:
––
––
––
––
Iris
Iris transillumination
transillumination
Hypopigmentation
Hypopigmentation of
of the
the retinal
retinal pigment
pigment epithelium
epithelium
Foveal
Foveal hypoplasia
hypoplasia // dysplasia
dysplasia
Optic
Optic nerve
nerve head
head morphology
morphology
•• Variability
Variability depends
depends on:
on:
––
––
Genotype
Genotype
Ethnical
Ethnical background
background
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Joel
Joel Benton:
Benton: Visit
Visit and
and
Aquisitions
Aquisitions at
at the
the Zoo
Zoo
(Life
(Life of
of Hon.
Hon. Phineas
Phineas T.
T. Barnum,
Barnum,
Edgewood
Edgewood Publishing
Publishing Company,
Company,
Philadelphia
Philadelphia 1891)
1891)
"I
"I went
went through
through scores
scores of
of
booths,
booths, where
where curiosities
curiosities and
and
monstrosities
monstrosities of
of all
all kinds
kinds were
were
exhibited,
exhibited, and
and was
was able
able to
to
make
make some
some purchases
purchases and
and
engagements
engagements for
for the
the American
American
Museum.
Museum.
Among
Among these
these was
was the
the Albino
Albino
family,
family, consisting
consisting of
of aa man,
man, his
his
wife,
wife, and
and son,
son, who
who were
were by
by far
far
the
the most
most interesting
interesting and
and
attractive
attractive specimens
specimens of
of their
their
class
class II had
had ever
ever seen."
seen."
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Lucassie
Lucassie Family
Family
Milestones of Research
•• Garrod
Garrod AE:
AE: Inborn
Inborn errors
errors of
of metabolism,
metabolism, Lecture
Lecture II
II
Lancet
Lancet 2,
2, 73-79,
73-79, 1908
1908
–– Albinism
Albinism was
was first
first described
described as
as aa disorder
disorder of
of metabolism
metabolism
•• Trevor-Roper
Trevor-Roper PD:
PD: Marriage
Marriage of
of two
two complete
complete albinos
albinos with
with
normally
normally pigmented
pigmented children
children
Br
Br JJ Ophthalmol
Ophthalmol 36,
36, 107-109,
107-109, 1952
1952
–– First
First clues
clues for
for genetic
genetic heterogeneity:
heterogeneity: normally
normally pigmented
pigmented
children
children from
from aa pair
pair of
of parents
parents who
who both
both had
had albinism
albinism
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Main
Main Types
Types of
of Albinism,
Albinism,
Chromosome
Chromosome and
and Gene
Gene
Subtypes
Subtypes (11
(11 Genes,
Genes, 17
17 Types)
Types)
OCA
OCA 3:
3:
OCA
OCA33(up
(upto
tonow
nowonly
onlydescribed
describedininAfrican
Africanpersons)
persons)
(Red
(rufous)
Albinism)
(Red (rufous) Albinism)
OCA
OCA 4:
4:Mutations
Mutationsim
imMATP-Gen,
MATP-Gen,Chromosome
Chromosome55
OCA
OCA44(Lit.:
(Lit.:Murray
Murray2002:
2002:one
oneTurkish
Turkishperson
personliving
livinginin
Germany;
Germany;own
ownstudy:
study:44persons
persons(3
(3Germans,
Germans,11Belgium)
Belgium)
Mutations
MutationsininTyrosinase-Gene,
Tyrosinase-Gene,Chromosome
Chromosome11
11
OCA2:
OCA2:
Mutations
Mutationsininthe
theTRP1-Gene,
TRP1-Gene,Chromosome
Chromosome99
Syndromes
Syndromeswith
with oculocutaneous
oculocutaneousAlbinism
Albinism
HPS1
HPS1::Chromosome
Chromosome10
10
HPS2
:
Chromosome
HPS2 : Chromosome 55
HPS3
HPS3::Chromosome
Chromosome 33
HPS4
HPS4::Chromosome
Chromosome22
22
(HPS1-Gene)
(HPS1-Gene)
(Adaptin,
(Adaptin,AP3B1-Gene)
AP3B1-Gene)
(HPS3-Gene)
(HPS3-Gene)
(HPS4-Gene)
(HPS4-Gene)
CHS:
CHS:Chromosome
Chromosome11(CHS-Gene)
(CHS-Gene)
Ocular
OcularAlbinism
Albinism
X-Chromosome
X-Chromosome(OA1-Gene)
(OA1-Gene)
Hermansky-Pudlack-Syndrome
Hermansky-Pudlack-Syndrome(HPS)
(HPS)
Typen
HPS
1,2,3,4
Typen HPS 1,2,3,4
Chediak-Higashi-Syndrome
Chediak-Higashi-Syndrome(CHS)
(CHS)
OA1:
OA1:Type
TypeNettleship-Falls
Nettleship-Falls
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
May 2003
2003
of research:
research: May
quo of
Status quo
Status
Mutations
Mutationsininthe
theP-Gene,
P-Gene,Chromosome
Chromosome15
15
OCA1A
OCA1A
OCA1B
OCA1B
OCA1B
OCA1BTS
TS(Temperature
(Temperaturesensitive)
sensitive)
OCA1B
MP
(Minimal
Pigment)
OCA1B MP (Minimal Pigment)
OCA1B
OCA1BYA
YA(Yellow
(YellowMutant,
Mutant,Yellow
YellowAlbinism)
Albinism)
OCA2
OCA2
Prader-Willi-Syndrome
Prader-Willi-Syndrome(PWS)
(PWS)
Angelman-Syndrome
(AS)
Angelman-Syndrome (AS)
OCA1:
OCA1:
Hauptgruppen,
Hauptgruppen, Gen
Gen
und
und Chromosom
Chromosom
Untergruppen
Untergruppen (11
(11 Gene,
Gene, 17
17 Typen)
Typen)
Mutationen
Mutationenim
imP-Gen,
P-Gen,Chromosome
Chromosome15
15
OCA1A
OCA1A
OCA1B
OCA1B
OCA1B
OCA1BTS
TS(Temperatursensitiv)
(Temperatursensitiv)
OCA1B
MP
(Minimal-Pigment)
OCA1B MP (Minimal-Pigment)
OCA1B
OCA1BYA
YA(Gelbmutante,
(Gelbmutante,Yellow
YellowAlbinism)
Albinism)
OCA2
OCA2
Prader-Willi-Syndrome
Prader-Willi-Syndrome(PWS)
(PWS)
Angelman-Syndrom
(AS)
Angelman-Syndrom (AS)
OCA
OCA 3:
3:
OCA
OCA33(bislang
(bislangnur
nurnur
nurbei
beiAfrikanern
Afrikanernbeschrieben)
beschrieben)
(Roter
(Roter(rufous)
(rufous)Albinismus)
Albinismus)
OCA
OCA 4:
4:Mutationen
Mutationenim
imMATP-Gen
MATP-Gen
OCA
OCA44(bislang
(bislangerst
ersteinmal
einmalbei
beieinem
einemTürken
Türkenaus
aus
Deutschland
Deutschlandbeschrieben)
beschrieben)
OCA1:
OCA1:
Mutationen
Mutationenim
imTyrosinase-Gen,
Tyrosinase-Gen,Chromosom
Chromosom11
11
OCA2:
OCA2:
Mutationen
Mutationenim
imTRP1-Gen,
TRP1-Gen,Chromosom
Chromosom99
Chromosom
Chromosom55
Syndrome
Syndromemit
mit okulokutanem
okulokutanemAlbinismus
Albinismus
HPS1
HPS1::Chromosom
Chromosom10
10
HPS2
:
Chromosom
HPS2 : Chromosom 55
HPS3
HPS3::Chromosom
Chromosom 33
HPS4
HPS4::Chromosom
Chromosom22
22
(HPS1-Gen)
(HPS1-Gen)
(Adaptin,
(Adaptin,AP3B1-Gen)
AP3B1-Gen)
(HPS3-Gen)
(HPS3-Gen)
(HPS4-Gen)
(HPS4-Gen)
CHS:
CHS:Chromosom
Chromosom11(CHS-Gen)
(CHS-Gen)
Okulärer
OkulärerAlbinismus
Albinismus
X-Chromosom
X-Chromosom(OA1-Gen)
(OA1-Gen)
Hermansky-Pudlack-Syndrome
Hermansky-Pudlack-Syndrome(HPS)
(HPS)
Typen
HPS
1,2,3,4
Typen HPS 1,2,3,4
Chediak-Higashi-Syndrom
Chediak-Higashi-Syndrom(CHS)
(CHS)
OA1:
OA1:Type
TypeNettleship-Falls
Nettleship-Falls
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Phaenotypic
Phaenotypic examples,
examples, three
three main
main albinism
albinism types
types
Confirmed
Confirmed by
by molecular
molecular genetic
genetic analysis
analysis
OCA1
OCA1
OCA2
OCA2
OCA1,
OCA1, OA
OA
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
OA
OA
Distribution of the types of albinism
N
N == 309
309 Persons
Persons
Types
9,93%
3,19%
25,53%
OCA1
OCA2
OA
Syndrome
unklar
17,38%
unclear:
unclear: nn =
= 34
34
43,97%
Syndromes:
-PWS
-HPS
••
••
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Phaenotype
Phaenotype not
not conclusive
conclusive
Moleculargenetical
Moleculargenetical analysis
analysis
not
not yet
yet finished
finished
Age
Age distribution
distribution
Paediatric
Paediatric ophthalmologic
ophthalmologic department!
department!
Age distribution
N = 309 Persons
70
High number of patients due to the
Head of the department being the
medicval advisor to NOAH Germany
Number of Patients
60
NOAH
NOAH
50
40
National
National
Organisation
Organisation for
for
Albinismus
Albinismus and
and
Hypopigmentation
Hypopigmentation
30
20
10
0
5,00
15,00
25,00
35,00
45,00
55,00
65,00
75,00
10,00
20,00
30,00
40,00
50,00
60,00
70,00
Age (years)
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
www.albinismus.info
www.albinismus.info
www.albinism.org
www.albinism.org
Phaenotype
Phaenotype evident
evident for
for OCA
OCA 1A
1A
Chr.
Chr. 11,
11, TYR-Gen
TYR-Gen
No
No pigment
pigment formation;
formation; formerly
formerly called:
called: „tyrosinase-negative“
„tyrosinase-negative“
Arabian
Arabian brother
brother and
and sister
sister
Characteristics
Characteristics
-- no
no pigmentation
pigmentation ever
ever
-- no
no correlation
correlation of
of phaenotype
phaenotype to
to ethnic
ethnic background
background
-- fast
fast diagnosis
diagnosis due
due to
to evident
evident findings
findings
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Phaenotype
Phaenotype typical
typical for
for OCA
OCA 22
Chr.
Chr. 15,
15, P-Gen
P-Gen
Clear
Clear pigment
pigment formation;
formation; formerly
formerly called:
called: „tyrosinase-positive“
„tyrosinase-positive“
Turkish
Turkish boy
boy –– phenotype
phenotype
different
different from
from family!
family!
Characteristics
Characteristics
-- different
different degrees
degrees of
of pigment
pigment formation
formation
-- obvious
obvious correlation
correlation of
of phaenotype
phaenotype to
to ethnic
ethnic background
background
-- often
often delayed
delayed diagnosis
diagnosis due
due to
to near
near to
to normal
normal phaenotype
phaenotype
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Phaenotype
Phaenotype of
of OCA
OCA 33
Rufous
Rufous albinism,
albinism, up
up to
to now
now only
only described
described in
in Africa
Africa
Characteristics
Characteristics
-- reddish
reddish hair
hair colour
colour
-- no
no further
further pigmentation
pigmentation
Father
Father and
and mother
mother of
of our
our patient:
patient:
immigrants
immigrants from
from Ghana
Ghana
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Problems
Problems in
in phaenotypical
phaenotypical differentiation
differentiation
OCA
OCA 1B,
1B, OCA2:
OCA2: both
both are
are pigment
pigment forming!
forming!
Therefore
Therefore Tyrosinase-negative
Tyrosinase-negative and
and –positive
–positive not
not applicable!
applicable!
Characteristics
Characteristics
-- paenotypical
paenotypical no
no differentiation
differentiation between
between OCA1
OCA1 and
and OCA2
OCA2 possible!
possible!
-- even
even dark
dark naevi
naevi are
are possible
possible in
in OCA1B
OCA1B
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Problematic
Problematic differentiation
differentiation by
by phaenotype
phaenotype
OCA
OCA 1B,
1B, OCA2:
OCA2: both
both pigment
pigment forming!
forming!
Look
Look out
out for
for pigmentation
pigmentation of
of eye
eye lashes!
lashes!
OCA1B:
OCA1B: often
often slightly
slightly darker
darker as
as scalp
scalp hair
hair
OCA2:
OCA2: mostly
mostly same
same colour
colour as
as scalp
scalp hair
hair
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Phaenotype
Phaenotype of
of OA
OA (Ocular
(Ocular Albinism)
Albinism)
Two
Two boys:
boys: OCA1A,
OCA1A, OA
OA
Charakteristika
Charakteristika
-- Eyes:
Eyes: any
any colour
colour possible
possible
-- Cutaneous
Cutaneous type:
type: skin
skin type
type II –– IV
IV possible
possible
-- Always:
Always: typical
typical family
family history
history
-- Typical:
Typical: Mother
Mother shows
shows signs
signs of
of carrier
carrier status!
status!
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Peculiarities
Peculiarities in
in Phaenotype
Phaenotype
Africans,
Africans, Afro-Americans
Afro-Americans
OCA3,
OCA3, African
African girl
girl as
as shown
shown
In
In former
former slide
slide
Boy,
Boy, aged
aged 22 yrs.
yrs.
Father
Father African
African
OCA1A
OCA1A
OCA2,
OCA2, African
African girl
girl
Characteristics
Characteristics
-- besides
besides OCA3
OCA3 (rufous)
(rufous) all
all types
types of
of albinism
albinism possible!
possible!
-OCA2:
-OCA2: Africans
Africans often
often show
show characteristic
characteristic long
long deletion
deletion on
on PP
-- OCA3
OCA3 often
often with
with better
better visual
visual function
function than
than OCA1
OCA1 and
and OCA2
OCA2
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Peculiarities
Peculiarities in
in Phaenotype
Phaenotype
„The
„The Red
Red Troops“
Troops“
Characteristics
Characteristics
-- Molecular
Molecular genetics:
genetics: OCA
OCA 22 or
or up
up to
to now
now no
no mutation
mutation detectable
detectable
-- presumed
presumed unknown
unknown gene
gene location?
location?
-- very
very large
large span
span of
of visual
visual function
function (if
(if in
in doubt:
doubt: perform
perform Albino-VEPC!)
Albino-VEPC!)
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Peculiarities
Peculiarities in
in Phaenotype
Phaenotype
Be
Be aware
aware of
of surprises
surprises in
in phaenotype
phaenotype and
and function!
function!
D.W.
D.W.
A.W.
A.W.
Both
Both siblings:
siblings:
mol.-gen.
mol.-gen. analysis:
analysis: OCA2
OCA2
Visual
Visual acuity
acuity OD/OS
OD/OS 20/20
20/20
No
No strabism
strabism
Both
Both sisters:
sisters:
Turkish
Turkish family,
family, gen.
gen. analysis:
analysis: OCA2
OCA2
Nystagmus
Nystagmus
Visus
Visus um
um 0,1
0,1
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Peculiarities
Peculiarities in
in Phaenotype
Phaenotype
OCA1B
OCA1B and
and OCA2
OCA2 often
often show
show gain
gain of
of pigmentation
pigmentation during
during childhood
childhood
African
African girl
girl had
had been
been as
as
pale
pale as
as newborn
newborn brother
brother
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Peculiarities
Peculiarities in
in Phaenotype
Phaenotype
Skin
Skin
Neurodermitis
Neurodermitis slightly
slightly
more
more frequent
frequent than
than in
in
average
average population.
population.
Nape
Nape naevus
naevus (Unna*´s
(Unna*´s mark)
mark)
frequent
frequent in
in all
all forms
forms of
of OCA
OCA
*Unna,
*Unna, Paul:
Paul: German
German dermatologist,
dermatologist, 1850
1850 -- 1929
1929
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Hauptgruppen,
Hauptgruppen, Gen
Gen
und
und Chromosom
Chromosom
Untergruppen
Untergruppen (11
(11 Gene,
Gene, 17
17 Typen)
Typen)
OCA2:
OCA2:
Mutationen
Mutationen im
im P-Gen,
P-Gen, Chromosome
Chromosome 15
15
OCA2
OCA2
Prader-Willi-Syndrome
Prader-Willi-Syndrome (PWS)
(PWS)
Angelman-Syndrom
Angelman-Syndrom (AS)
(AS)
OCA
OCA 3:
3:
OCA
OCA 33 (bislang
(bislang nur
nur nur
nur bei
bei Afrikanern
Afrikanern beschrieben)
beschrieben)
(Roter
(Roter (rufous)
(rufous) Albinismus)
Albinismus)
Mutationen
Mutationen im
im TRP1-Gen,
TRP1-Gen, Chromosom
Chromosom 99
OCA
OCA 4:
4: Mutationen
Mutationen im
im MATP-Gen
MATP-Gen
Chromosom
Chromosom 55
OCA
OCA 44 (bislang
(bislang erst
erst einmal
einmal bei
bei einem
einem Türken
Türken aus
aus
Deutschland
Deutschland beschrieben)
beschrieben)
Syndrome
Syndrome mit
mit okulokutanem
okulokutanem Albinismus
Albinismus
HPS1
HPS1 :: Chromosom
Chromosom 10
10
HPS2
HPS2 :: Chromosom
Chromosom 55
HPS3
HPS3 :: Chromosom
Chromosom 33
HPS4
HPS4 :: Chromosom
Chromosom 22
22
(HPS1-Gen)
(HPS1-Gen)
(Adaptin,
(Adaptin, AP3B1-Gen)
AP3B1-Gen)
(HPS3-Gen)
(HPS3-Gen)
(HPS4-Gen)
(HPS4-Gen)
CHS:
CHS: Chromosom
Chromosom 11 (CHS-Gen)
(CHS-Gen)
Okulärer
Okulärer Albinismus
Albinismus
OA1-Gen,
OA1-Gen, X-Chromosom
X-Chromosom
Hermansky-Pudlack-Syndrome
Hermansky-Pudlack-Syndrome (HPS)
(HPS)
Typen
Typen HPS
HPS 1,2,3,4
1,2,3,4
Chediak-Higashi-Syndrom
Chediak-Higashi-Syndrom (CHS)
(CHS)
OA1:
OA1: Type
Type Nettleship-Falls
Nettleship-Falls
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
2003
May 2003
as of
of May
research as
of research
Status of
Status
Mutationen
Mutationen im
im Tyrosinase-Gen,
Tyrosinase-Gen, Chromosom
Chromosom 11
11
OCA1A
OCA1A
OCA1B
OCA1B
OCA1B
OCA1B TS
TS (Temperatursensitiv)
(Temperatursensitiv)
OCA1B
MP
OCA1B MP (Minimal-Pigment)
(Minimal-Pigment)
OCA1B
YA
(Gelbmutante,
OCA1B YA (Gelbmutante, Yellow
Yellow Albinism)
Albinism)
OCA1:
OCA1:
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and Genetics
Genetics
••Oculocutaneous
Oculocutaneous albinism
albinism
••Ocular
Ocular albinism
albinism
••Syndromes
Syndromes with
with oculocutaneous
oculocutaneous albinism
albinism
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Genetics / Heredity
Single
Single human
human set
set of
of chronosomes
chronosomes
Associated
Associated with
with different
different forms
forms
of
of albinism:
albinism:
99 chromosomes
chromosomes
11
11 gene
gene loci
loci
11
33
55
99
10
10
11
11
15
15
22
22
XX
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
CHS-Gen
CHS-Gen
HPS-3-Gen
HPS-3-Gen
MATP-Gen
MATP-Gen –– OCA4
OCA4
AP3B1-Gen
AP3B1-Gen –– HPS2
HPS2
TRP1-Gen
TRP1-Gen –– OCA3
OCA3
HPS1-Gen
HPS1-Gen
TYR-Gen
TYR-Gen –– OCA2
OCA2
P-Gen
P-Gen –– OCA2
OCA2
HPS4-Gen
HPS4-Gen
OA1-Gen
OA1-Gen
Bislang
Bislang bekannte
bekannte Mutationen
Mutationen
Graphiken
Graphiken mit
mit freundlicher
freundlicher Genehmigung
Genehmigung von
von Prof.
Prof. Dr.
Dr. R.
R. King,
King, Albinism
Albinism Database,
Database, Minneapolis
Minneapolis
TYR
P
OA
TRP1
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Heredity
•• All
All oculocutaneous
oculocutaneous forms:
forms:
••
autosomale-recessive
autosomale-recessive
Ocular
Ocular albinism
albinism ::
X-chromosomale-recessive
X-chromosomale-recessive
––
––
Only
Only boys
boys affected
affected
Always
Always conductor
conductor signs
signs in
in
mother
mother
–– Seldom
Seldom mildly
mildly affected
affected
mothers
mothers
Typical
Typical pedigree
pedigree of
of aut.-recessive
aut.-recessive
heredity
heredity // manifestation
manifestation
Gene
frequency
in
Europa
/
Norhtern
US
(caucasian
popul.)
Gene frequency in Europa / Norhtern US (caucasian popul.)
Heterogenous
11 :: 100
Heterogenous gene
gene carrier:
carrier:
100
Albinism:
11 :: 17.000
Albinism:
17.000
~
BRD:
BRD:
~ 4700
4700 affected
affected persons
persons
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Classic
Classic autosomale-recessive
autosomale-recessive heredity
heredity in
in OCA1A
OCA1A
One
One sibling:
sibling: Conductor,
Conductor, very
very pale
pale skin
skin complexion
complexion
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Heredity
Tipps
Tipps for
for an
an orientating
orientating counselling
counselling
•• Always
Always recommend
recommend counselling
counselling at
at an
an Institute
Institute of
of Human
Human Genetics!
Genetics!
•• Thumb
Thumb rule:
rule:
–– With
With one
one affected
affected child
child
•• 25%
25% morbidity
morbidity risk
risk for
for every
every further
further child
child (different
(different phenotypes
phenotypes possible)
possible)
•• 50%
50% risk
risk of
of heterozygote
heterozygote gene
gene carrier
carrier (conduktor)
(conduktor)
•• 25%
25% probability
probability of
of genetical
genetical normality
normality
––
––
11 parent
parent wirh
wirh albinism:
albinism: risk
risk 1:200
1:200 to
to have
have an
an affected
affected child
child
22 parents
parents with
with albinism
albinism
•• Genetically
Genetically same
same type:
type: children
children will
will be
be affected
affected 100%
100%
•• Genetically
Genetically different
different type:
type: risk
risk 1:200
1:200
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Moleculargenetic
Moleculargenetic Analysis
Analysis
•
•
•
Difficult!! Routine or prenatal analysis not possible in Europa / USA
Reasons for problems of moleculargenetic analysis
–– Even
Even in
in analysis
analysis 1/3
1/3 of
of patients
patients without
without results
results
•• further
further up
up to
to now
now unknown
unknown gene
gene loci
loci are
are probable
probable
–– Some
Some of
of the
the 11
11 genes
genes are
are very
very big
big extensive
extensive sequencing
sequencing
Own 2 studies in cooperation with Würzburg (79 pts.) and Lübeck (179 pts.)
–– Specrtrum
Specrtrum of
of mutations
mutations different
different than
than in
in the
the USA
USA
–– Many
Many new
new mutations
mutations were
were detected
detected
–– Up
Up to
to now:
now: 22%
22% of
of persons
persons without
without results
results
–– OCA4
OCA4
••
••
•
Literature:
Literature: one
one description
description worldwide
worldwide
Actual
Actual study:
study: 44 persons
persons (2
(2 Germans,
Germans, 11 Belgium,
Belgium, 11 Luxembourg)
Luxembourg) have
have OCA4
OCA4
Praenatal diagnosis: not sensibly possible
(exception: skin biopsy in known OCA1A as performed ion Corea and China)
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
The spectrum of albinism
•• Table
Table of
of content
content and
and course
course of
of lecture
lecture
–– Types
Types of
of albinism
albinism and
and genetics
genetics
••Oculocutaneous
Oculocutaneous albinism
albinism
••Ocular
Ocular albinism
albinism
••Syndromes
Syndromes with
with oculocutaneous
oculocutaneous
albinism
albinism and
and paediatric
paediatric specialities
specialities
––
––
Ophthalmologic
Ophthalmologic and
and orthoptic
orthoptic specialities
specialities
Neuroanatomic
Neuroanatomic specialities
specialities
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Albinism
Albinism
Syndromes
Syndromes relevant
relevant to
to the
the Paediatrician
Paediatrician
•• Paediatric
Paediatric aspects
aspects in
in caring
caring for
for albinism
albinism persons
persons
–– Syndromes
Syndromes
•• Hermansky-Pudlack-Syndrome
Hermansky-Pudlack-Syndrome HPS
HPS
•• Chediak-Higashi-Syndrome
Chediak-Higashi-Syndrome CHS
CHS
•• Prader-Willi-Syndrome
Prader-Willi-Syndrome PWS
PWS
•• Angelman-Syndrome
Angelman-Syndrome AS
AS
––
––
Always
Always albinism
albinism
Occasionally
Occasionally albinism
albinism
Hypopigmentation
Hypopigmentation and
and skin
skin protection
protection
Socio-medical
Socio-medical and
and educational
educational counselling
counselling due
due to
to
the
the visual
visual impairmant
impairmant
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Hermansky-Pudlak-Syndrome
Hermansky-Pudlak-Syndrome
OMIM-Entry
OMIM-Entry 203300;
203300; 44 Types,
Types, 44 Genes,
Genes, Chr.
Chr. 3,5,10,22
3,5,10,22
•• Pigment
Pigment forming
forming OCA
OCA with
with variable
variable degrees
degrees of:
of:
––
––
––
––
––
––
––
Prolonged
Prolonged bleeding
bleeding time
time
Granulomatous
Granulomatous colitis
colitis
Interstitial
Interstitial lung
lung fibrosis
fibrosis
Renal
Renal insufficiency
insufficiency
Cardiomyopathy
Cardiomyopathy
Live
Live expectancy
expectancy possibly
possibly reduced
reduced
Diagnostic
Diagnostic proof:
proof:
•• missing
missing dense
dense bodies
bodies in
in thromocytes
thromocytes
–– Electron
Electron microscopy
microscopy
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Chediak-Higashi-Syndrome
Chediak-Higashi-Syndrome
OMIM-Entry
OMIM-Entry 214500;
214500; Chr.
Chr. 1:
1: CHS-Gene
CHS-Gene
•• Pigment
Pigment forming
forming OCA
OCA with
with variable
variable degrees
degrees of:
of:
––
––
––
––
––
––
––
High
High risk
risk of
of infection
infection // sepsis
sepsis
Hepato-Splenomegaly
Hepato-Splenomegaly
Muscular
Muscular weakness
weakness // atrophy
atrophy
Progressive
Progressive mental
mental impairment
impairment
Progressive
Progressive neurologic
neurologic degeneration,
degeneration, brain
brain atrophy
atrophy
Life
Life expectancy
expectancy always
always reduced
reduced
Diagnostic
Diagnostic proof:
proof:
•• Giant
Giant granula
granula in
in muscle
muscle and
and nervous
nervous tissue
tissue
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Prader-Willi-Syndrome
Prader-Willi-Syndrome
OMIM-Entry
OMIM-Entry 176270,
176270, Chr.
Chr. 15,
15, 15-20%
15-20% have
have OCA2
OCA2
•• Distinct
Distinct retardation
retardation of
of mental
mental and
and motoric
motoric development:
development:
–– Learning
Learning and
and mental
mental impairment
impairment
–– PWS
PWS =
= one
one of
of the
the most
most frequent
frequent forms
forms of
of learning
learning impairments
impairments
––
––
––
––
––
Short
Short statue
statue
Adipositas,
Adipositas, pathognominic:
pathognominic: always
always hungry
hungry
Sociually
Sociually unbalanced
unbalanced behaviour
behaviour
Genital
Genital hypoplasia
hypoplasia
Hypopigmentation
Hypopigmentation
–– In
In 70%
70% pale
pale skin
skin and
and fair
fair hair
hair
–– In
In 20%
20% eye
eye symptoms
symptoms and
and clinical
clinical OCA2
OCA2
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Angelman-Syndrome
Angelman-Syndrome
Happy-Puppet-Syndrome
Happy-Puppet-Syndrome
OMIM-Entry
OMIM-Entry 105830;
105830; Chr.
Chr. 15,
15, seldom
seldom associated
associated with
with OCA2
OCA2
•• Severe
Severe mental
mental impairment
impairment and
and pathognomonic
pathognomonic
paroxysmal
paroxysmal laughing
laughing bouts
bouts with:
with:
––
––
––
––
––
––
Often
Often inability
inability to
to learn
learn to
to speak
speak
Ataxia
Ataxia
Epileptic
Epileptic seizures
seizures
Microbrachycephaly,
Microbrachycephaly, Prognathia
Prognathia
Cutaneous
Cutaneous hypopigmentation
hypopigmentation
Ocular
Ocular hypopigmentation
hypopigmentation
–– Nystagmus
Nystagmus and
and visual
visual impairment
impairment in
in approx.
approx. 10%
10%
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Albinism
Albinism –– Summary
Summary of
of Syndromes
Syndromes
•• HPS
HPS and
and CHS
CHS
––
––
––
Always
Always pigment
pigment forming
forming OCA
OCA
rare,
rare, HPS
HPS >
> CHS
CHS
Reduced
Reduced life
life expectancy
expectancy possible
possible
•• PWS
PWS und
und AS
AS
––
––
PWS
PWS frequent,
frequent, AS
AS rare
rare
Albinismus
Albinismus in
in ca
ca 15%
15%
•• in
in all
all cases
cases of
of mental
mental impairment
impairment PWS
PWS and
and AS
AS
and
and visual
visual impairment
impairment need
need to
to be
be ruled
ruled out!
out!
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan
Ru/Ks
Ru/Ks oder
oder Ks/Ru.
Ks/Ru. The
The Spectrum
Spectrum of
of Albinism.
Albinism. Name
Name der
der Tagung,
Tagung, June
June 2003,
2003, Kobe,
Kobe, Japan
Japan