Acta Dermato-Venereologica 99-1CompleteContent | Page 32
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SHORT COMMUNICATION
Schöpf-Schulz-Passarge Syndrome: Previously Unreported WNT10A Genotype and Phenotypes in
9 Family Members
Corinna E. ZIMMERMANN 1 , Muhidien SOUFI 2 , Volker RUPPERT 3 , Juergen R. SCHAEFER 2 and Helmut VON DOMARUS 1
Clinic of Oral and Maxillofacial Surgery, Breite Strasse 44–46, DE-23552 Lübeck, 2 Center for Undiagnosed and Rare Diseases (ZusE), and
Department of Cardiology, University Hospital Giessen and Marburg, Marburg, Germany. E-mail: [email protected]
1
3
Accepted Sep 27, 2018; Epub ahead of print Sep 28, 2018
Schöpf-Schulz-Passarge Syndrome (1) (SSPS, ORPHA:
50944; OMIM: 224750; ICD-10: Q82.8) is a rare geno-
dermatosis characterized by multiple cysts on the eyelids
(apocrine hidrocystomas), palmo-plantar keratoderma, hypo-
dontia, hypotrichosis, and nail dystrophy. While hypodontia
can be diagnosed during childhood, the hallmark of SSPS
(2, 3), hidrocystomas of the eyelids, develop at an advanced
age, and, thus, SSPS may occasionally be underdiagnosed.
The mode of inheritance and the underlying genetic funda-
mentals have not been completely identified. Most of the 38
documented cases of SSPS are single or within 1 generation.
Recently, mutations of the WNT family member (WN-
T10A) gene have been linked to various ectodermal dyspla-
sias (ED), e.g. odonto-onycho-dermal dysplasia (OODD)
(4), including SSPS (3, 5). The WNT10A gene is expressed
during multiple developmental processes including skin,
tooth, hair, and nail embryogenesis. In adult tissues, WNT10A
is involved in tooth and hair follicle morphogenesis by in-
hibiting the ß-catenin degradation pathway.
We recruited 14 family members from 2 generations for
clinical and genetic analysis of symptoms of SSPS (Fig.
S1 1 ). Patient examination included medical history and
physical examination. Informed consent for DNA analysis,
publication of data and photographs was obtained from
all patients. Ethical aspects were in accordance with the
principles outlined in the Declaration of Helsinki. Blood
samples of all 14 participants were taken and analysed in
the same manner. For molecular genetic analysis patients’
DNA was extracted and all coding exons of the WNT10A
gene were amplified by PCR and Sanger sequenced in
forward and reverse directions in all family members. Da-
tabase searches for variant analysis were performed in the
Human Gene Mutation Database (HGMD public), Exome
Variant Server (EVS), Ensembl and ExAC.
CASE REPORTS
Patient 1. A 53-year-old man (IV.2 in the pedigree, Fig. 1A) pre-
sented with multiple cystic lesions along the margins of his eyelids
since his mid-40s. Histological examination revealed apocrine
hidrocystoma. He reported severely callused skin of palms and
soles with painful fissuring since his early 20s. His finger nails, and
particularly his toe nails, were fragile and malformed. He denied
excessive sweating. At age 17 years, he received partial dentures,
because only 6 permanent tooth had developed. His primary den-
tition had been normal. No permanent teeth had been removed.
From the same age onwards, he noticed decreased growth of hair.
Three years before presentation, a basal cell carcinoma of the right
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3055
1
Fig. 1. Patients 1 (IV.2) (A), 2 (IV.3) (B) and 3 (IV.7) (C) with numerous
(recurrent) 1–2 mm clear or bluish cystic lesions of translucent or milky
opacity bilaterally on the upper and lower eyelid margins.
cheek had been removed. Genetic analysis identified 2 heterozy-
gous nonsense mutations in exon 2 (c.321C>A;p.Cys107*) and
exon 3 (c.742C>T;p.Arg248*) of the WNT10A gene (Fig. S2 1 ).
Patient 2. The 51-year-old sister (IV.3) of patient 1 showed similar
symptoms including eyelid cysts (Fig. 1B), keratoderma of the
palms and soles, and oligodontia with only 8 permanent teeth pre-
sent. For the past 1.5 years her nails had become dystrophic with
hypoplasia, splitting, longitudinal furrows, and ridging. Her scalp
hair was dry; she had sparse eyebrows and no hair on the legs and
axillae. She reported not sweating at all and having xerostomia. Ge-
netic analysis identified the same nonsense mutations as in patient 1.
Patient 3. The 46-year-old sister (IV.7) of patient 1, reported cal-
lused skin of the palms and soles with painful fissures, agenesis of
3 permanent teeth, and recurrence of previously removed eyelid
cysts (Fig. 1C). Genetic analysis identified a nonsense mutation
of only 1 allele (p.Arg248*).
Patient 4. The 25-year-old daughter (V.3) of patient 1 exhibited no
eyelid cysts, but mild keratoderma, nail dystrophy, and agenesis of
5 permanent teeth. She reported that her scalp hair never became
greasy. Genetic analysis identified the same nonsense mutation
as in patient 3.
Patient 5. The 8-year-old daughter (V.7) of patient 3 had very dry,
slowly growing scalp hair and agenesis of 5 permanent teeth. Ge-
netic analysis identified the same nonsense mutation as in patient
3 (for phenotypes see Fig. S3 1 ).
Four further family members were heterozygous carriers of one
of the 2 mono-allelic nonsense mutations, but showed no features of
SSPS. In the remaining 5 family members no mutations of the WN-
T10A gene were detected (wild type) and no symptoms were noted.
This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta
Journal Compilation © 2019 Acta Dermato-Venereologica.
doi: 10.2340/00015555-3055
Acta Derm Venereol 2019; 99: 113–114