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LAURENCE-MOON-BARDET-BIEDL SYNDROME IN ISRAEL
E. N. EHRENFELD, M.D., H. ROWE, AND E. AUERBACH, M.D.
Jerusalem, Israel
The L a u r e n c e - M o o n - B a r d e t - B i e d l (LMBB) syndrome is characterized by a pentad of congenital defects: poly- or syn-dactyly, mental retardation, obesity, hypo-genitalism and tapetoretinal dystrophy. The latter often appears in the form of retinitis. pigmentosa. Some signs of the syndrome were first described by Laurence and Moon1
in 1866. Bardet2 added polydactyly in 1920 as an essential sign, and Biedl3 pointed out its familial occurrence two years later. Additional features are sometimes found such as congenital heart disease, deafness, strabismus, neurologic and renal involvement.
Though the etiology of the syndrome is not known and chromosomal studies have not yet yielded any abnormal findings, the disorder is unanimously considered to be of heredodegenerative nature. The total parental consanguinity rate of 25 to 40% points to an autosomal recessive mode of inheritance.4
The LMBB syndrome is not a very common disorder ; until 1958 less than 300 cases were reported in the literature,5 and many of these did not display all the cardinal signs.
It is likely that abortive forms of the syndrome exist, since there are reports of finding some, but not all of the cardinal signs in siblings of patients with characteristic disease.6 In addition to the criteria established by external morphological findings, the diagnosis of tapetoretinal degeneration was readily established in those cases submitted to electrophysiologic studies.7
We studied the incidence of LMBB in the groups of various ethnic backgrounds comprising the Jewish population of Israel, and we have reason to believe that we have ex-
From the Endocrinology Clinic and the Vision Research Laboratory of the Wolf son's Ophthalmo-logical Research Laboratories, Hadassah University Hospital and Medical School, Jerusalem, Israel.
Reprint request to E. N. Ehrenfeld, M.D., Endocrinology Clinic, Hadassah University Hospital, P.O. Box 499, Jerusalem, Israel.
amined practically all the cases. We also included cases from the Arab population of the country. There is no doubt, however, that our coverage of the Arab cases was not comprehensive; therefore, this material is not included in the statistical treatment.
MATERIAL AND METHODS
An effort was made to find all patients with LMBB in this country by contacting all the eye departments. Fifteen patients, aged 10 months to 23 years, were examined. The consanguineous parents of three unrelated patients among the 15 stated they had had several stillbirths in the past, and each had one child that died in its infancy. These three deceased infants were obese and had supernumerary fingers and toes. Although not examined by us, there is little doubt that they represent genuine cases of LMBB, and are consequently included in the statistical calculations of this study.
General clinical examinations were possible in all 15 patients seen in the laboratory, but only in 11 was it possible to do electroretinograms (ERG) and obtain the visual evoked response (VER) of the striate cortex. These tests were performed in an electrically shielded room. Stroboscopic light flashes of about 10 milliseconds' duration (van Gogh photostimulator SI1A) were used in both tests. The ERG response was measured in both eyes between a corneal electrode and one fastened to the skin at the midsupra-orbital rim. The responses were elicited by single stimuli and recorded by a condenser-coupled dual beam oscilloscope (Tektronix 502). The VER was derived between two scalp electrodes fixed at the median line at the union and 5 cm above it. For recording, the CAT (Mnemotron 400B) was used, which averaged the responses to 70 flashes given manually at a rate of roughly one per second. In both cases, the responses were photo-
524
VOL. 70, NO. 4 LAURENCE-MOON SYNDROME 525
graphed from the screen of the oscilloscope. In addition to these tests, the retinal response to intermittent stimuli from 5 to 70 c/s (nicker ERG) was recorded in seven patients.
Color vision could not be examined reliably owing to the low intelligence of the patients. The ophthalmoscopic findings and those of the visual field and the visual acuity, as well as the results from the electrophysio-logic examinations are summarized in Table 1.
RESULTS
The 18 patients (including the three deceased infants) descended from 12 families, nine of which were Jewish and three Arab. Of these, 11 were boys. Physical findings are summarized in Table 2. In eight families the parents were first cousins, and in one of these an additional intermarriage was found in the ascendancy. Ten of the Jewish patients were born in Israel and three abroad (two in Rumania, one in Algeria). The Arab patients were all born in this country.
In addition to the cardinal pentad, other abnormalities were found in several patients. In one patient, pathologic changes in the eyes were found which apparently were not connected with the tapetoretinal degeneration. Two other patients had congenital heart disease, two had kidney disease, and another had unilateral hip luxation (Tables 1 and 2) . This lesion was also found in a sister of another patient, who showed no sign of the LMBB.
All patients examined were night-blind. They all had congenital malformations of their extremities, hypogenitalism and were mentally defective. They were also obese. All had polydactyly, sometimes syndactyly in at least one extremity. The supernumerary digit was always very short. In some cases, two or three other digits of the affected limb were also abnormally short. The polydactyly usually was of the postaxial type. There seemed to be a preference for an additional finger at the ulnar side, and of an additional toe at the lateral side of the foot.
The polydactyly was found in all four limbs in 10 patients of the 15 examined. However, in some of the other cases, a rudiment of an additional digit could be found by x-ray in the essentially unaffected extremity (Table 2) .
The mental capacity was reduced to various levels in all 15. Even in patients seen early in life, mental development was found to be greatly impaired, and the severe and progressive loss in vision may represent an additional aggravating factor, hampering mental development still further. On the other hand, some patients appeared quite restless; some were even aggressive.
Hypogenitalism is difficult to ascertain in children, particularly in girls in the presence of obesity. The four girls over age 11 all had delayed sexual development, with the onset of menstruation around the age of 17. A few of the boys had cryptorchism.
Owing to the mental retardation, the subjective tests of visual acuity, visual fields, and color vision did not provide reliable results. However, vision was found to be very low in all cases but one in which visual acuity of 5/18 was found. The visual fields were always markedly constricted (Table 1).
The fundus picture was similar in most cases. It was not always typical for retinitis pigmentosa, though in most instances it displayed tapetoretinal degeneration with waxy disks, constricted blood vessels and missing or scarcely visible foveal reflex. In some patients there were glittering white spots. Only in five cases, all above the age of 10 years, were the typical bone corpuscles found. In another patient the pigment was of the pepper-and-salt type.
The ERG was extremely low or even extinct. Extinction of the retinal response was defined by the absence of any ERG, even when measured by the CAT. Among the 11 patients examined, the youngest had the largest ERG, with an overall positive amplitude of about 40 μν (the normal range of the ERG amplitude under our test conditions is from 400 to 550 μν). The flicker ERG was extinct in all cases for all frequencies from 5 to 70
TA
BL
E 1
FIN
DIN
GS
IN V
AR
IOU
S ST
UD
IES
MA
DE
IN
15
PAT
IEN
TS
WIT
H L
AU
RE
NC
E-M
OO
N-B
AR
DE
T-B
IED
L SY
ND
RO
ME
Cas
e V
isua
l N
o.
Acu
ity
Nys
tagm
us,
Cat
arac
t, Sq
uint
N
ight
V
isio
n C
oloi
V
isio
n Fu
ndus
V
isua
l Fi
elds
E
RG
Fl
icke
r V
ER
1.
3/60
3.
F.C
. at
2
m
4.
F.C
. at
1
m
5.
5/18
wit
h co
rrec
tion
6.
6/60
7.
F.C
. at
C
onve
rgen
t 1-
2 m
sq
uint
lef
t ey
e
9.
6/60
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
*
Unc
lass
ifie
d de
fect
Dis
ks s
light
ly p
ale;
ves
sels
alm
ost
nor-
*
mal
; no
fove
al r
efle
x; n
o pi
gmen
t; hy
per-
refle
xion
Pale
dis
ks;
tem
pora
l ch
oroi
dal
conu
s V
ery
mor
e in
the
rig
ht e
ye; b
lood
ves
sels
ver
y co
nstr
icte
d na
rrow
; no
fov
eal
refl
ex;
no p
igm
ent
in
the
left
eye;
a s
mal
l pi
gmen
t cr
esce
nt i
n th
e ri
ght;
seve
ral
isol
ated
, gli
tter
ing
spot
s
Prac
tica
lly
Ext
inct
E
xtin
ct
exti
nct
Ext
inct
E
xtin
ct
Ver
y sm
all
Seve
re
' ni
ght
blin
dnes
s
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
* Pa
le d
isks
; bl
ood
vess
els
very
nar
row
; no
fov
eal
refl
ex;
no p
igm
ent
* C
hara
cter
isti
c ch
ange
s fo
r re
tini
tis
pigm
ento
sa
* C
hara
cter
isti
c ch
ange
s fo
r re
tini
tis
pigm
ento
sa
Dis
ks o
val,
pale
, blo
od v
esse
ls n
arro
w,
pigm
ent
in f
ine
spot
s w
ith
few
whi
tish
do
ts (
pepp
er-a
nd-s
alt
fund
us)
Seve
re
Def
ectiv
e D
isks
pal
e, n
o fo
veal
ref
lex,
ves
sels
ni
ght
blin
dnes
s m
oder
atel
y na
rrow
ed,
som
e at
ypic
al
pigm
ent
*
Ver
y co
nstr
icte
d
*
Ver
y co
nstr
icte
d
*
The
pat
ient
is
bed-
ridd
en
Ext
inct
*
Ext
inct
Ext
inct
E
xtin
ct
> g W
to P 1—
I o c to
> r O
Tj O a H
X > r o r o o o n H
O
W
M
to
TA
BL
E 1
(Con
tinue
d)
Cas
e V
isua
l N
o.
Acu
ity
Nys
tagm
us,
Cat
arac
t, Sq
uint
Nig
ht
Col
or
Vis
ion
Vis
ion
Fund
us
Vis
ual
Fiel
ds
ER
G
Flic
ker
VE
R
< O
2 o 10
11
6/60
Nys
tagm
us,
pin
poin
t pu
pils
, B
ila
tera
l co
ngen
ital
cata
ract
s
Nys
tagm
us
12
F.C
. 2
m
Div
erge
nt s
quin
t ri
ght
eye
13
F.C
. }
m
—
14
F.C
. N
ysta
gmus
15
6/60
16
F.C
. 1 m
N
ysta
gmus
18
RE
: F.
C.
2 m
L
E:
5/30
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Seve
re
nigh
t bl
indn
ess
Cou
ld n
ot b
e ex
amin
ed
* D
isks
nor
mal
col
or, b
ut a
bnor
mal
sha
pe,
Ver
y bl
ood
vess
els
narr
owed
onl
y in
per
iph-
co
nstr
icte
d er
y, f
ovea
l re
flex
pres
ent,
who
le f
undu
s da
rkis
h, b
ut n
o pi
gmen
t, se
vera
l ar
eas
wit
h ch
oroi
dal
atro
phy
Tri
tano
pia
Dis
ks n
orm
al c
olor
, ve
ssel
s sl
ight
ly
Ver
y na
rrow
ed,
dark
fun
dus,
no
pigm
ent
cons
tric
ted
Def
ectiv
e D
isks
slig
htly
pal
e, v
esse
ls n
arro
wed
, no
V
ery
fove
al r
efle
x, b
lack
pig
men
t, m
acul
ar
cons
tric
ted
chan
ges
(?)
* N
o pi
gmen
t, di
ffic
ult
to s
ee f
undu
s be
- *
caus
e of
sev
ere
nyst
agm
us a
nd l
ack
of
coop
erat
ion
* D
isks
pal
e, b
lood
ves
sels
slig
htly
nar
- *
row
ed,
fove
al r
efle
x sl
uggi
sh,
no p
igm
ent
* D
isks
pal
e, le
ft ey
e m
ore
wax
y th
an
Ver
y ri
ght,
fove
al r
efle
xes
pres
ent,
chor
oida
l co
nstr
icte
d ch
ange
s, n
o pi
gmen
t *
Dis
ks p
ale,
ves
sels
nar
row
ed,
typi
cal
Ver
y pi
gmen
t co
nstr
icte
d
40 μ
ν
20μν
Ext
inct
Ext
inct
Ext
inct
Ext
rem
ely
smal
l
Ext
inct
5
μν
Ext
inct
Ext
inct
E
xtin
ct
The
pat
ient
is
bed-
ridd
en
Ext
inct
Ext
inct
Ext
inct
E
xtin
ct
—
Ext
inct
> a fo
M
O w I o o ΧΛ <<
σ o M
* T
est
coul
d no
t be
per
form
ed b
ecau
se p
atie
nt d
id n
ot u
nder
stan
d or
did
not
coo
pera
te, o
r th
e re
sult
s w
ere
not
relia
ble
(pat
ient
s N
os.
2, 8
, an
d 17
had
die
d be
fore
stu
dy b
egan
and
no
data
is
avai
labl
e).
to
TA
BL
E 2
PER
SON
AL
DA
TA A
ND
FIN
DIN
GS
IN 1
8 C
ASE
S O
F L
MB
B
SYN
DR
OM
E
528
Cas
e A
ge
Sex,
Con
san-
Fa
mil
y N
o.
(Yea
rs)
guin
ity
Ori
gin
Oth
er
Sibl
ings
A
ffec
ted
Poly
dact
yly
or
Synd
acty
ly
„,
. M
enta
l „
...
Oth
er
Obe
sity
R
eta
rd
ati
on
Hyp
ogen
itah
sm
De
fec
ts
Rem
arks
1 2 3 4 5 6 7 8 9
6 3 20
23
11
10 7 8
wee
ks
7
M
F M
F M
F M
M
F
No
No
No
No
Yes
Yes
Yes
Yes
Yes
Tuni
sia
Tuni
sia
Rum
ania
Rum
ania
Yem
en
Yem
en
Isra
el
(par
ents
fro
m
Pola
nd)
Isra
el
(par
ents
fro
m
Pola
nd)
Rum
ania
Sist
er
(Cas
e 2)
B
roth
er
(Cas
e 1)
Sist
er
(Cas
e 4)
B
roth
er
(Cas
e 3)
Sist
er
(Cas
e 6)
Bro
ther
(C
ase
5)
Bro
ther
(C
ase
8)
Bro
ther
(C
ase
7)
No
6 di
gits
on
each
ex
trem
ity
6 di
gits
on
each
ex
trem
ity
6 di
gits
on
each
ex
trem
ity
6 di
gits
on
each
ex
trem
ity
6 fin
gers
on
left
hand
6 di
gits
on
each
ex
trem
ity
6 fin
gers
on
right
ha
nd
6 di
gits
on
each
ex
trem
ity
6 to
es o
n ea
ch
foot
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Not
kno
wn
yes
Not
obv
ious
Not
kno
wn
Yes
Yes
Yes
Yes
Not
obv
ious
Not
kno
wn
Not
ass
essa
ble
Con
geni
tal
kidn
ey
dise
ase
Con
geni
tal
hear
t di
seas
e
Con
geni
tal
kidn
ey
dise
ase
Con
geni
tal
hear
t di
seas
e
Die
d at
age
3
Unc
le o
bese
, cou
sin h
ad d
efor
med
fe
et,
mot
her
was
dia
betic
B
ed-r
idde
n, s
ame f
amily
as C
ase
3
Mot
her
has
nyct
alop
ia
Die
d at
age
eig
ht w
eeks
, m
othe
r ha
s ny
ctal
opia
Mot
her
has
nyct
alop
ia a
nd b
ila
tera
l co
ngen
ital
cata
ract
s,
mot
her's
fat
her
and
twin
bro
th
ers
had
cong
enita
l ca
tara
cts
AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1970
TA
BL
E 2
(Con
tinue
d)
< O r 3 o > C
to
M o M
I o o C/J κί
Ö
?a
O
Cas
e N
o.
10
11
12
13
14
IS
16
17
18
Age
(Y
ears
)
10
mon
ths
7 19
18
21
10 7 1
wee
k
14
Sex
Con
san
guin
ity
M
F M
F M
F M
M
M
No
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
Fam
ily
Ori
gin
Mor
occo
Iraq
Iraq
Alg
ier
Ara
b
Ara
b
Ara
b
Ara
b
Ara
b
Oth
er
Sibl
ings
A
ffec
ted
No
No
No
No
Sist
er
(Cas
e 15
) B
roth
er
(Cas
e .1
4)
Bro
ther
C
ase
17)
Bro
ther
(C
ase
.16)
No
Poly
dact
yly
or
Synd
acty
ly
6 di
gits
on
each
ex
trem
ity
6 to
es o
n ri
ght
foot
6 fin
gers
on
righ
t ha
nd
6 fin
gers
on
righ
t ha
nd
and
6 to
es o
n le
ft fo
ot
6 fin
gers
on
righ
t ha
nd a
nd 6
toe
s on
rig
ht f
oot
6 di
gits
on
each
ex
trem
ity
6 to
es o
n ea
ch
foot
6 di
gits
on
each
ex
trem
ity
6 di
gits
on
each
ex
trem
ity
Obe
sity
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Men
tal
Ret
arda
tion
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Not
kno
wn
Yes
Hyp
ogen
ital
ism
Not
ass
essa
ble
Not
ass
essa
ble
Yes
Not
obv
ious
(m
enar
che
age
17)
Yes
Not
ass
essa
ble
(age
)
Not
ass
essi
ble
(age
)
Not
kno
wn
Not
cle
ar
Oth
er
Def
ects
Bil
ater
al
cong
enita
l ca
tara
cts
Uni
late
ral
cong
enit
al
righ
t hi
p lu
xati
on
Rem
arks
Dou
ble
cons
angu
init
y in
par
ents
Sist
er
had
unil
ater
al
cong
enit
al
hip
luxa
tion
Fath
er i
s de
af;
mot
her
is d
eaf
and
dum
b
A b
roth
er h
as n
ycta
lopi
a
Bed
-rid
den,
bro
ther
has
ny
ctal
opia
Die
d w
hen
one
wee
k ol
d
Neo
nata
l de
ath
in t
wo
brot
hers
an
d tw
o si
ster
s
530 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1970
c/s. In those cases in whom central vision was still preserved, the VER was measurable. However, the amplitude elicited was very small and the latent period very lengthened. In seven cases the VER was completely absent.
Siblings of patients with LMBB were not included in 'this study when they showed only part of the classic pentad and other abnormalities instead. However, it is worth noting that a brother of patient No. 14 was night-blind and somewhat mentally retarded. He did not show, however, distinct signs of tapetoretinal degeneration, and his ERG pointed to congenital night-blindness rather than to the latter causation. The mothers of two patients (Nos. 7 and 9) complained of night-blindness and this complaint was corroborated by an abnormal ERG; both these women married their first cousins.
In one patient (No. 13), a urine sample was examined for the presence of excess mucopolysaccharides by three tests : The ec-teola dip test, precipitation with 65% metha-nol and examination of the precipitate for mucopolysaccharide components, and dialysis and direct examination for mucopolysaccharide components. None of the three tests indicated abnormally high excretion of mucopolysaccharides.
DISCUSSION
In this study, 15 well-defined cases of the Laurence-Moon-Bardet-Biedl syndrome are added to the literature. Since the etiology of the disorder is unknown, only those cases were included which clearly showed the classic pentad. This restriction seems necessary until specific biochemical, sérologie, or cyto-genetic criteria are found. It is even more important because some signs of the syndrome appear either as part of other syndromes in various combinations or together with acoustic, vestibular, central nervous system, cardiac, or renal manifestations.8"13
Some variations may occur even in otherwise normal members of the same family.6
Polydactyly and other digital malforma
tions, although displaying considerable variations in different patients, are of great diagnostic value as they are mostly easily noticed. There are cases, however, where only an x-ray examination will reveal the deformity. In others, only a scar from a plastic operation points to the abnormality.
A constant and objective sign which ap-pears-early in life is an ophthalmoscopic picture that is characteristic or at least suggestive of tapetoretinal degeneration. However, the pigment changes typical for retinitis pig-mentosa do not appear regularly or early ; if present, they are generally seen only later in life. They were found in only five of our patients, and all of these were above the age of 10. Inferior visual acuity, severe night-blindness, and constricted visual fields are generally observed at an early age by the parents. These signs often lead the physician to the recognition of early changes in the fundus. These are, however, often atypical, and the final diagnosis must be obtained by ERG.
Hypogonadism, although considered a major feature of the pentad, is most variable. Even cases of precocious puberty may occur.14
Many women with normal ovarian function have been seen and some were even fertile.15 Men may have normal testicular function and morphology,16'17 moderate sperma-togenic impairment,18'19 or germinal aplasia.20
The hypogonadism, if present, may then be either of hypogonadotropic21'22 nature (secondary hypogonadism) or be due to deficient function of the gonads (primary hypogonadism).20,23 Hypogonadism is often difficult to determine in prepuberal children, particularly in girls.
The other two constituents forming part of the classical pentad, obesity and mental retardation are difficult to measure and tests for the latter are not easily assessed objectively. Therefore, although present to varying degree in our patients, these criteria only supplement the other features.
In addition to the classic signs of the syndrome, other abnormalities were found in some of the patients.
VOL. 70, NO. 4 LAURENCE-MOON SYNDROME 531
Renal changes occurring in patients with the LMBB syndrome have been found in necropsies,24 but have rarely been diagnosed in vivo. This series includes two patients with the LMBB syndrome in whom definite renal abnormalities were diagnosed clinically and radiologically. One of these patients (No. 5) was reported previously.13 The other (No. 7) displayed renal insufficiency secondary to hypoplastic kidneys.
Two cases, (Nos. 6 and 8) suffered from congenital heart disease. One died in infancy and the other could not be studied in great detail because of her many other problems.
One patient (No. 11), an offspring of double first cousins, had unilateral congenital hip luxation.
As two of the patients (Nos. 5 and 6) could not be traced at the time of the survey, they were not included in the statistical evaluation. Therefore, we refer to 11 Jewish children suffering from the LMBB syndrome who were detected in Israel in recent years. Nine of them, belonging to eight families, were alive in 1968. Their ages varied from six to 23 years. The Jewish population in Israel at the end of 1967 in the age group 0-24 was 1.2 million.25
The origins of the eight families are varied. Three families originated in Europe and five derived from Asia and Africa. This distribution was compared to that of the total Israeli population (continent of birth, or for those born in Israel, continent of birth of father). At the end of 1967, considering only the population in the age group 0-24 years, 39% are of European origin while the rest stem from Asia and Africa. This proportion of 3 : 8 and 5 : 8, respectively, is very similar to the composition of the Jewish population, and does not indicate that the disease is more prevalent in any one of the population groups, unlike other heredofamilial diseases such as Tay-Sachs, Gaucher, or familial Mediterranean fever.26
As this syndrome seems to be caused by a rare recessive gene, the frequency of consanguineous marriages among parents of
TABLE 328
ETHOS OF 18 PATIENTS STUDIED
Country
Rumania* Poland* Iraqf Morocco and Tunisiat
First Cousins and Closer Relation
ship
(%) 2.0 1.6
17.5 7.1-12.1
* Ashkenazi Jews t Non-Ashkenazi Jews
affected individuals is expected to be high. The rate of 50% in our series is somewhat higher than that reported by others.4 This may be because of the rather high rate of consanguineous marriages in Israel (Table 3).28 The rate of 11 boys to 7 girls is in accordance with reported data.27
As to the three Arab families, a pedigree of persons from this country suffering from this syndrome has been described previously29
and it is not included in this series. Cases of the LMBB syndrome may be de
tected in infancy when referred for removal of supernumerary digits, or later, when visual problems arise and they are referred to an ophthalmologist. More rarely they are sent for consultation because of hypogenital-ism, obesity or mental retardation. All specialists dealing with one of these disturbances should be alert to the signs of the syndrome.
SUMMARY
Eighteen patients from Israel (11 boys) suffering from the Laurence-Moon-Bardet-Biedl syndrome showed the classical pentad. Some exhibited additional abnormalities sometimes associated with this syndrome. Beside the clinical evaluation, their electroret-inogram and visual evoked response were measured and the diagnosis of tapetoretinal degeneration was confirmed, even when the fundus picture was not typical. The patients were derived from 12 families, nine Jewish and three Arab. In six of the Jewish and in
532 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1970
the three Arab families, the parents of the patients were first cousins. No predilection for any specific ethnic group was found, in contrast to some other heredodegenerative and metabolic diseases.
Addendum: Since this paper was submitted for publication, two monographs that deal with this subject have appeared in print, one in Switzerland30 and the other in Holland.31
ACKNOWLEDGMENTS
We thank Dr. T. Cohen, from the Department of Human Genetics, for statistical and genetic evaluation of the material, and Professor E. R. Berman, from the Biochemistry Research Laboratory, Department of Ophthalmology, for the investigation of excretion of excess mucopolysaccharides in the urine.
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4. Williams, R. H.: Textbook of Endocrinology, 4th ed. Philadelphia, W. B. Saunders, 1968, p. 1152.
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26. Heller, H., Gafni, J., and Sohar, E. : In Stan-bury, J. B., Wyngaarten, J. B., and Fredrickson, D. S. L. : The Metabolic Basis of Inherited Diseases, 2nd ed. New York, McGraw-Hill, 1960, chap. 42, Table 47-6, p. 1007.
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31. Stigglebout, W. : The (Laurence-Moon) Bardet-Biedl syndrome. Amsterdam, Van Gorcum, 1969.
