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Acta Derm Venereol 94
SHORT COMMUNICATION
Acta Derm Venereol 2014; 94: 459–460
© 2014 The Authors. doi: 10.2340/00015555-1714
Journal Compilation © 2014 Acta Dermato-Venereologica. ISSN 0001-5555
Acute and chronic UV exposure is an important risk
factor leading to photocarcinogenesis, photoimmuno-
suppression and photoaging (1, 2). Patients with Gorlin
syndrome (GS) harbour a hereditary predisposition to
develop basal cell carcinomas (BCC) and are, therefore,
advised that effective sun protection is essential and can
help reduce skin cancer risk (1–4). On the other hand,
adherence to strict sun-protection habits can result in
vitamin D deciency, which has been demonstrated in
many patients with GS (2, 3). Vitamin D deciency is
associated with an increased risk of osteomalacia, bone
fractures, autoimmune diseases, cancer and cardiovas-
cular disease (1).
CASE REPORT
Here, we report a 54-year-old man with GS who was
admitted to our hospital for surgical treatment of multiple
BCC (Fig. 1). Characteristic features of GS were present
in the form of multiple BCC since youth, palmoplantar
pits, an odontogenic cyst, calcication of the falx cerebri,
and positive family history (5). DNA analysis by
m
ulti-
plex
l
igation-dependent
p
robe
a
mplication revealed a
novel heterozygous deletion of exons 11 and 12 within
the PTCH1 gene, leading to a frame shift and premature
termination codon. Moreover, the patient’s medical his-
tory revealed that within the past decades, multiple bone
fractures had occurred after minimal trauma, suggesting
a bone calcication disorder. The patient reported of his
strict photoprotection habits by daily textile and cosmetic
sun protection measures as well as trying to avoid sun
exposure. Laboratory work-up including parameters of
bone turnover and metabolism showed serum 25(OH)D
levels of < 4 ng/ml, far below the normal range (30–70
ng/ml), elevated alkaline phosphatase and low serum
phosphate concentrations. Serum calcium, parathyroid
hormone and vitamin A, E and K concentrations were
within normal ranges. Dual-energy X-ray absorptiometry
(DEXA) was consistent with severe osteoporosis ac-
cording to the WHO classication, with a mean T-score
of –3.6 measured from the hip (Fig. 2). Based on these
observations, we concluded that the patient suffered from
a disorder of bone mineralisation caused by vitamin D
deciency. Substitution therapy was initiated with a
single dose of intramuscularly administered vitamin
D3 derivative (cholecalciferol 100,000 IU) followed by
long-term daily oral substitution of 2,000 IU of vitamin
D3. The 25(OH)D level was within the normal range 3
months after initiation of therapy.
Vitamin D deciency has been described in GS pa-
tients and is thought to be related to strict sun protection
habits (1–3). The time of vitamin D measurement in
our patient was spring (April), where probands usually
have higher vitamin D levels than during winter (2), but
they were still below the detection limit of the labora-
tory test. Normal serum levels of the other lipophilic
vitamins (vitamins A, E, K) argue against an intestinal
malabsorption disorder or an imbalanced overall nu-
tritional vitamin supply in our patient. There were no
signs of renal or hepatic insufciency which could have
inuenced vitamin D metabolism (6).
DISCUSSION
Vitamin D deciency is well-known in GS patients (3),
but no data have so far been available regarding the
clinical relevance (2). Our patient experienced multiple
bone fractures due to insufcient bone mineralisation
and had a high need for vitamin D substitution.
The present case shows that strict photoprotec-
tion habits of GS patients are a double-edged sword.
Iatrogenic Vitamin D Deciency in a Patient with Gorlin Syndrome: The Conundrum of
Photoprotection
Sabrina Gentzsch1, Johannes S. Kern1, Stefan Loeckermann1, Eva Geissler1, Jochen Seufert2, Carsten Bernard3, Juergen
Kohlhase3, Leena Bruckner-Tuderman1 and Frank Meiss1
1Department of Dermatology, University Freiburg – Medical Center, Hauptstrasse 7, DE-79104 Freiburg, 2Division of Endocrinology and Diabetology, Depart-
ment of Internal Medicine II, University Hospital Freiburg, and 3Center for Human Genetics, Freiburg, Germany. E-mail: frank.meiss@uniklinik-freiburg.de
Accepted Jun 26, 2013; Epub ahead of print Nov 6, 2013
Fig. 1. The patient presented with multiple basal cell carcinomas on the
head, a typical feature for Gorlin syndrome.
460 Short communication
Therefore, we strongly support the plea for analysis
of vitamin D levels in GS patients (3). Moreover, a
thorough screening for clinical features heralding a
vitamin D deciency is recommended. Interestingly, in
vitamin D receptor decient mice (serving as model of
vitamin D deciency), BCC development was shown
after UV exposure and was attributed to overactivation
of the hedgehog signalling pathway, which is also the
pathophysiological basis for BCC development in GS
patients (7, 8). Hence, iatrogenic vitamin D deciency
of GS patients could even represent an environmental
factor enhancing BCC development in these individuals.
ACKNOWLEDGEMENT
We thank Prof Dr. Rudolf Happle for his critical and helpful
revision of the manuscript.
The authors declare no conflicts of interest.
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Fig. 2. (a) Dual-energy X-ray-absorptiometry (DEXA)
of the left hip. (b) T-score of –2.6 (black square) for the
neck of the femoral bone (bone mineral density: BMD).
(c) Results of DEXA showing BMD, T-score, Z-score and
percentage compared to indicated reference population
(young adults, age match) at different regions of the left
hip and mean values.
Acta Derm Venereol 94