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Schöpf-Schulz-Passarge syndrome (SSPS)

Written2012-07John A McGrath
St John's Institute of Dermatology, King's College London (Guy's Campus), London, United Kingdom

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Identity

Other namesKeratosis palmoplantaris with cystic eyelids, hypodontia, and hypotrichosis.
Eccrine tumours with ectodermal dysplasia.
Atlas_Id 10138
Genes implicated inWNT10A  
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).

Clinics

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-onycho-dermal 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.
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.
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

 
Gene NameWNT10A
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, 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.

To be noted

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.

Bibliography

Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.
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WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes.
Bohring A, Stamm T, Spaich C, Haase C, Spree K, Hehr U, Hoffmann M, Ledig S, Sel S, Wieacker P, Ropke A.
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Two families confirm Schopf-Schulz-Passarge syndrome as a discrete entity within the WNT10A phenotypic spectrum.
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Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases.
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Schopf-Schulz-Passarge syndrome resulting from a homozygous nonsense mutation in WNT10A.
Nagy N, Wedgeworth E, Hamada T, White JM, Hashimoto T, McGrath JA.
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Schopf-Schulz-Passarge syndrome resulting from a homozygous nonsense mutation, p.Cys107X, in WNT10A.
Petrof G, Fong K, Lai-Cheong JE, Cockayne SE, McGrath JA.
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Eccrine syringofibroadenoma: multiple lesions representing a new cutaneous marker of the Schopf syndrome, and solitary nonhereditary tumors.
Starink TM.
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Phenotypic variability associated with WNT10A nonsense mutations.
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Intra-familial variability of ectodermal defects associated with WNT10A mutations.
Wedgeworth EK, Nagy N, White JM, Pembroke AC, McGrath JA.
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Citation

This paper should be referenced as such :
McGrath, JA
Schè_pf-Schulz-Passarge syndrome (SSPS)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(12):940-942.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Tumors/SchopfSchulzPassargeID10138.html


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