Clin Genet 1996: 49: 28-31 Copyrinht 0 Munksnaard 1996

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CLINICAL GENETI-&
ISSN ooo9-9/63

The spectrum of ocular features in the

Williams-Beuren svndrome
Winter M. Pankau R, Amm M, Gosch A, Wessel A. The spectrum of ocular
features in the Williams-Beuren syndrome.
Clin Genet 1996: 49: 28-3 1.0 Munksgaard, 1996
One hufidred and fifty-two patients with the Williams-Beuren syndrome were
examined to assess the frequency and severity of ophthalmological features as-
sociated with the disorder. Eighty-two (54%) had strabismus, all but three, es-
otropia. One hundred and seventeen (77%) patients had blue irides, 10 (7%)
green, and 25 (16%)brown. One hundred and twelve (74%) showed a typical
so-called stellate iris pattern of the anterior strorna. Whitish anomalies were
also detectable in brown irides. Two 9-year-old patients and one 46-year-old
patient had initial cataract.Of all the patients with funduscopy, 22%had retinal
vascular tortuosity. One patient had suspected Rieger syndrome. Two patients
had ptosis, one with a Marcus-Gum phenomenon. No ncular manifestation of
hypercalcaemia was noted.
M. Winter', R. Pankau2,
Marita Amm', Angela GoschZ
and A. Wesse13
Departmentsof 'Ophthalmology and *Pediatrics,
University of Kiel and 3Department of Pediatric
Cardiology, University of GBttingen, Germany
Key words: iris -strabismus - Williams-Beuren
syndrome
Dr. med. Martin Winter, Klinik fiir
Ophthalmologie, Hegewischstr. 2, 24105 Kiel,
Germany
Received 12 July 1994, revised version received
6 April, accepted for publication 20 August 1995

The Williams-Beuren syndrome (WBS) is an auto-
soma1 dominant hereditary disorder with psychomo-
tor retardation, distinctive facial features, cardiovas-
cular anomalies, postnatal growth retardation and a
characteristic personality (Williams et al. 1961,
Beuren et al. 1962, Dilts et al. 1990, Pankau et al.
1992). The syndrome may or may not be associated
with idiopathic infantile hypercalcaemia (Kruse et
al. 1992). Systemic hypertension is frequently diag-
nosed during childhood (Daniels et al. 1985). Sev-
eraI authors (Williams et al. 1961, Jones & Smith
1975, Greenberg & Lewis 1988, Holmstrom et al.
1990) have described ocular features in W B S pa-
tients. They mention a stellate iris stromal pattern,
strabismus, and tortuosity of the major retinal ves-
sels as being characteristic for this syndrome. As
part of a large study on WBS, we investigated 152
patients to assess the frequency and severity of ocu-
lar findings.
Patients and methods
From 1988 to 1994, re-examinations of 152 patients
(66 females, 86 males) with a positive diagnosis of
W B S were performed by one paediatrician and
geneticist (R.P.). The ages ranged between 6 months
and 46 years, with a'median age of 9.0 years. Fifty-
two of these patients (24 females, 28 males; age
range: 1.7 - 46.7 years, median: 5.5 years) were also
examined by an ophthalmologist. Among these 52
patients, a test for visual acuity was possible in 25
patients (14 females, 11 males, age range: 4.8 - 46.7
years, median: 6.7 years). An indirect ophthalmo-
scopy of the ocular fundus was possible in 46
patients (23 females, 23 males; age range: 2.3 - 46.8
years, median: 11.3 years).
Results
A typical WBS face was seen in 128 of the 152
patients (84%; 55 females, 73 males, Fig. la,b). All
showed normal eyelids, except for two patients with
bilateral ptosis. One of them had Marcus-Gunn phe-
nomenon. Another patient had been operated
because of a lacrimal duct stenosis. Eighty-two
(54%) of the patients showed strabismus or had a
case history of strabismus. In all but three strabis-
mus convergens was diagnosed. Of these patients,
19 had undergone surgical correction, but nine had
residual small-angle esotropia. Thirty-nine of the 63
patients who had not been operated were 5 years old
or younger.

Fig. la,b. Two patients with typical facial features of the Williams-Beuren syndrome. Notice retrouss6 nose, heavy orbital ridges, full
lips and wide open mouth. a.: 14-year-old patient with blue irides, b.: 19-year-old patient with brown irides.
Refractive errors were hyperrnetropia (average
spherical equivalent: +1.50; range: plano to +4:00)
in 17 of 25 patients. One of three patients with myo-
pia had anisometropia of -7.00 and -1.00. None had
astigmatism greater than 2.00 diopters.
One hundred and seventeen (77%) of all patients
had blue irides, 10 (7%) green, and 25 (16%)
brown. The combination of typical WBS face and
blue irides was seen in 104 patients. One hundred
and twelve (74%) of the 152 patients showed the
typical stellate pattern of the irides (Fig. 2a). In the
128 patients with characteristic facial features for
the syndrome, 98 (77%) showed an obvious stellate
pattern of the irides. The stroma of the iris had
coarse architecture and radial or cartwheel striation.
The iris collarette was usually absent or incomplete.
In contrast to the easily detectable stellate pattern in
blue irides, at first sight no patient with brown irides
showed these anomalies. With slit-lamp micro-
scopy, however, the detection of a whitish stellate
pattern in dark irides was also possible (Fig. 2b).
One male patient, aged 9 years, had suspected
Ocular features of William-Beuren syndrome
Rieger syndrome. He demonstrated anterior syn-
echia of the iris at 1 and 2 o'clock, hypoplasia of the
teeth, hypodontia and prognathism. Glaucoma had
not yet been diacmosed. The periumbilical skin was
normal.
Two 9-year-old patients (one male, one female)
showed a slight posterior clouding of the lens cap-
sula. The oldest female patient, aged 46 years,
showed initial cataract in both eyes.
During a period of hospitalisation, blood pressure
was documented for 50 patients aged between 6
months and 34 years. Eighty-two percent showed a
systolic blood pressure above the 95th centile, and
in 72% the diastolic blood pressure was pathologi-
cally high compared to the corresponding age
groups in the general population (Horan et al. 1987,
Diem et al. 1975).
In 18 of 46 patients the indirect ophthalmoscopic
examination showed a fundus without any anoma-
lies. Tortuosity of the retinal vessels was observed
in 22%: distinct tortuosity in seven patients, and ini-
tial tortuosity in three. The average age of these pa-
29
Winter et al.
Fig. 2a,b. a.: Right blue iris of same patient as in Fig. la. No-
tice coarse architecture, radial striation. b.: Right brown iris of
same patient as in Fig. lb. Notice the white brightenings on
raised trabeculas anterior to the usual stroma of the irides. .
tients was 11.5 years. High blood pressure was seen
in only one of them. Four patients had a hypopig-
mented fundus and six showed hyperpigmented
changes of the pi-ment epithelium. Pale optic discs
were seen in six patients and in another two, excur-
vated discs were noted. One patient showed a colo-
boma of the papilla. Atypical retinal vessels, and
bleeding next to the papilla or epipapillary connec-
tive tissue was observed in one patient.
All 152 patients were nomocalcaemic; in only
two was hypercalcaemia documented in childhood.
No ocular manifestations of hypercalcemia, such as
calcium deposits in the conjunctiva, calcific band
keratopathy of the cornea, or punctate opacities in
the lens or retina were noted.
30
Discussion
Since its initial description by Williams et al. in
1961 and Beuren et al. in 1962, many authors have
reported on ocular findings in the Williams-Beuren
syndrome. The most prominent ocular features are
strabismus (Jones & Smith 1975, Ott & Stengel-
Rutkowski 1985/86, Pagon et al. 1987) and the typi-
cal stellate pattern of the ins (Jones & S m i t h 1975,
Pagon et al. 1987). However, there have been few
reports on systematic investigations of the fre-
quency and severity of the ocular findings (Green-
berg & Lewis 1988).
In the literature the reported frequencies of stra-
bismus in WBS vary between 29% (Greenberg &
Lewis 1988) and 70% (Lopez-Range1 et al. 1992).
Our frequency figure (54%) is similar to that re-
ported by Pagon et al. (1987). This high frequency
contrasts dramatically with the reported incidence
of strabismus of about 5-7% in the general popula-
tion (deDecker 1986). For this reason, we agree
with Greenberg & Lewis (1988) that infants and
children with WBS should be investigated carefully
for the presence of strabismus. The low number of
patients with surgical correction in our collective
group may be due to the fact that about half of them
were 5 years old or younger. Regardless of an indi-
cation for surgical correction of strabismus, preven-
tion of amblyopia has to be in the focus of attention.
Our observation of a so-called stellate iris pattern
which was seen in 74%, agrees well with the 74%
reported by Jones & Smith (1975). Stellate iris pat-
tern as well as absence or incompleteness of the an-
terior iris collarette represent normal congenital var-
iations of the anterior iris structure. The ernbryolog-
ical origin and the significance of this frequent fea-
ture in WBS are unknown (Greenberg & Lewis
1988). There appears to be a high correlation be-
tween light (blue, green)-coloured irides and WBS.
First impressions that patients with dark (brown, ha-
zel) irides do not show the typical stellate pattern of
the stroma cannot be proven. Close slit-lamp obser-
vations show white brightenings on raised trabecu-
las anterior to the usual stroma of the ins. Therefore,
the typical stellate pattern of the iris in WBS pa-
tients also occurs in dark irides but is covered by
prominent pigment.
One 9-year-old male patient with blue irides
showed anterior synechia in combination with
hypo- and microdontia. The intraocular pressure
was normal. This is conspicuous for the Rieger syn-
drome. Glaucoma in the Rieger syndrome may oc-
cur between 5 and 30 years of age (Balacco-Gabrieli
et al. 1985). In the literature there is one previous re-
port of WBS and the Rieger syndrome published by
Balacco-Gabrieli et al. (1985).

Surprisingly we observed slight posterior cloud-
ing of the lens capsula in two 9-year-old patients.
There are no previous reports on early pathological
changes of the lens in WBS. Our finding of initial
cataract in these young patients is remarkable but
may be coincidental. The lenses of WBS patients
should be carefully observed.
Several authors (Martin et al. 1984, Culler et al.
1985, Martin et al. 1985) have mentioned hyper-
calcaemia as a frequent symptom of the syndrome.
Only two of our patients had been hypercalcaemic.
Ocular manifestations of hypercalcaemia were not
seen in these or in any of our other patients. Cer-
tainly, we did not carry out conjunctival biopsies to
confirm the absence of ocular manifestations of hy-
percalcaemia, as suggested by Jensen et al. (1976).
Indirect ophthalmoscopy identified changes of
the retinal vessels, of the papilla and of pigment epi-
thelium. None of the findings is of clinical relevance
for our patients, but the high frequency of these
changes is remarkable. In contrast to Greenberg &
Lewis (1988),who did not observe accentuated reti-
nal vascular tortuosity, we noted vascular abnormal-
ities in 10 (22%) of 46 patients undergoing fundu-
scopy.
Ocular features in WBS patients, such as strabis-
mus and retinal abnormalities, have potential implj -
cations and occur with relatively high frequency.
Apart from cardiovascular and renal diagnostics, we
therefore recommend detailed ophthalmologic ex-
amination and regular checks for all patients, espe-
cially for all infants and children with possible or
certain diagnosis of Williams-Beuren syndrome.
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