Download Cancer Prone Disease Section Schöpf Schulz Passarge syndrome (SSPS)

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Short Communication
Schöpf-Schulz-Passarge syndrome (SSPS)
John A McGrath
St John's Institute of Dermatology, King's College London (Guy's Campus), London, United Kingdom
(JAM)
Published in Atlas Database: July 2012
Online updated version : http://AtlasGeneticsOncology.org/Kprones/SchopfSchulzPassargeID10138.html
DOI: 10.4267/2042/48372
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Clinics
Other names
Keratosis palmoplantaris with cystic eyelids,
hypodontia, and hypotrichosis.
Eccrine tumours with ectodermal dysplasia.
Note
SSPS is an eponymous form of ectodermal dysplasia
first described in 1971 by Erwin Schöpf, Johann Schulz
and Eberhard Passarge in a report of two sisters with
eyelid cysts, hypodontia, hypotrichosis, palmoplantar
hyperkeratosis and nail dystrophy.
Inheritance
Autosomal recessive.
Fewer than 100 cases of SSPS have been reported.
Heterozygous carriers may show some ectodermal
anomalies (predominantly hair/nails in females,
teeth in males).
Phenotype and clinics
SSPS is characterized by eyelid cysts (apocrine
hidrocystomas),
palmoplantar
keratoderma,
hypodontia,
hyperhidrosis,
hypotrichosis
and
onychodystrophy, as well as other, often variable,
ectodermal developmental anomalies (Schöpf et al.,
1971; Monk et al., 1992).
SSPS shows clinical overlap with odonto-onychodermal dysplasia (OODD), but the eyelid cysts are a
typical sign of SSPS.
Some features may not present until adulthood and
diagnosis can be delayed (Granger et al., 2012).
The presence of ectodermal abnormalities in some
carriers can lead to confusion in the mode of
inheritance (Craigen et al., 1997).
Eyelid cysts (apocrine hidrocystomas) that can also extend to the peri-ocular regions and nasal bridge.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(12)
940
Schöpf-Schulz-Passarge syndrome (SSPS)
McGrath JA
p.Arg248X, and p.Cys376X), nine missense mutations
(p.Ile116Thr,
p.Arg128Gln,
p.Ala131Thr,
p.Ala131Val, p.His143Tyr, p.Val145Met, p.Phe228Ile,
p.Gly266Cys, and p.Arg360Cys) and one frameshift
mutation (p.Glu52fsX29) (Adaimy et al., 2007;
Bohring et al., 2009; Nagy et al., 2010; Wedgeworth et
al., 2011; van Geel et al., 2010; Catori et al., 2011;
Cluzeau et al., 2011; Petrof et al., 2011; Granger et al.,
2012). Of note, cases classified clinically as SSPS or
OODD may harbour the same WNT10A gene
mutation(s). The two most frequently observed
mutations are p.Cys107X and p.Phe228Ile. Moreover,
homozygous or compound heterozygous mutations
involving p.Cys107X have been found in both SSPS
and OODD, demonstrating that these two disorders are
indeed allelic and that the precise phenotypic
consequences are influenced by more than just this
particular mutation in WNT10A alone. There is no
genotype-phenotype correlation with regard to
neoplastic risk.
Neoplastic risk
The neoplastic risk in SSPS is controversial. Some
authors consider that SSPS can be associated with an
increased risk of benign as well as malignant skin
tumours (Monk et al., 1992). Reports include an
increased incidence of benign adnexal tumours, such as
eyelid hidrocystomas or eccrine syringofibroadenomas
(Starink, 1997), and possibly a higher risk of malignant
skin tumours such as squamous cell carcinoma, basal
cell carcinoma and eccrine porocarcinoma (Bohring et
al., 2009; Monk et al., 1992; Starink, 1997).
Treatment
There is no effective treatment for SSPS. Hyperhidrosis
of the palms may respond partially to tap water
iontophoresis (although use of anti-cholinergics may
induce excessive systemic side-effects such as dry
mouth, dizziness and drowsiness). Systemic retinoids
can exacerbate skin peeling, although low doses may
help some individuals. The apocrine hidrocystomas can
be improved by electrocautery. Regular skin
examination to detect non-melanoma skin cancer may
be advisable. Regular dental care/surgery is indicated in
most cases. Hair/nail cosmesis may help some
individuals. Psychological support should be offered, as
necessary.
To be noted
Note
It is also noteworthy that individuals who are
heterozygous for WNT10A mutations may show some
clinical abnormalities. Hair, nail, teeth and skin
abnormalities may all occur in heterozygotes; this
probably accounts for the initial difficulties in
classifying SSPS/OODD as either autosomal dominant
or autosomal recessive disorders (the latter is correct).
The mutation p.Phe228Ile appears to have a population
frequency of ~0,5% and it has been estimated that
approximately half of all individuals who are
heterozygous for this missense mutation will manifest
some form of ectodermal defects (Bohring et al., 2009).
This equates to ~1 in 400 of the general population
displaying some clinical anomaly affecting hair, teeth,
nails, sweat glands, or a combination thereof, as a
direct consequence of this WNT10A gene sequence
variant.
Evolution
Many of the features of ectodermal dysplasia only
manifest or worsen during adulthood. In some
individuals with SSPS, the apocrine hidrocystomas
tend to become larger and more numerous with age.
Prognosis
Life expectancy is normal; the main challenge is the
symptomatic management of whichever ectodermal
pathologies cause the patient the most concern.
Genes involved and proteins
WNT10A
Location
2q35
Note
WNT10A is a key signalling molecule that regulates
cell-cell interactions and which is involved in multiple
developmental processes in embryogenesis. In adult
tissues it inhibits the β-catenin degradation complex
and is involved in hair follicle and tooth morphogenesis
(Logan and Nusse, 2004).
Mutations
Note
Mutations in WNT10A underlie SSPS, OODD and
some cases of hypohidrotic ectodermal dysplasia. Thus
far, 16 different WNT10A mutations have been
reported. These include six nonsense mutations
(p.Trp9X, p.Cys107X, p.Arg128X, p.Glu233X,
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(12)
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Atlas Genet Cytogenet Oncol Haematol. 2012; 16(12)
This article should be referenced as such:
McGrath JA. Schöpf-Schulz-Passarge syndrome (SSPS). Atlas
Genet Cytogenet Oncol Haematol. 2012; 16(12):940-942.
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