| Clinical entity/subtype | Key features | Causal gene(s) | Inheritance | Example variant(s) mentioned in evidence | Key triggers/exacerbating factors | Key references (PMID/DOI) |
|---|---|---|---|---|---|---|
| Acral peeling skin syndrome (APSS) | Painless superficial peeling/exfoliation mainly of hands and feet; may include erythema, itching, erosions, flaccid blisters; histologic cleavage between stratum corneum and granular layer; can mimic localized epidermolysis bullosa simplex (pqac-00000000, pqac-00000003) | **TGM5** | Autosomal recessive (pqac-00000003, pqac-00000012) | p.Gly113Cys / c.337G>T; p.Trp255Arg / c.763T>C; c.2T>C p.M1T; c.1037G>A; c.684+1G>A (pqac-00000001, pqac-00000003, pqac-00000013) | Humidity, friction/trauma, perspiration/hyperhidrosis, heat, water/moisture (pqac-00000000, pqac-00000003, pqac-00000013) | DOI: 10.5114/dr.2023.131389; 10.2340/actadv.v104.24305; 10.1159/000354572; 10.1111/1346-8138.17422 |
| Acral peeling skin syndrome due to **CSTA** | Lifelong acral peeling; some reports note overlap with exfoliative ichthyosis/fine scaling; skin fragility related to impaired adhesion/protease inhibition (pqac-00000003, pqac-00000013) | **CSTA** (cystatin A) | Autosomal recessive (consanguineous pedigree; homozygous LOF) (pqac-00000013) | p.Lys22Ter / p.Lys22X nonsense mutation (pqac-00000013) | Heat, friction, perspiration, excessive moisture, exposure to water (pqac-00000013) | DOI: 10.1111/pde.12092 |
| Generalized PSS type A / non-inflammatory generalized PSS | Generalized superficial peeling/scaling beginning in early childhood; non-inflammatory generalized form (pqac-00000000, pqac-00000009, pqac-00000012) | **CHST8** | Autosomal recessive (pqac-00000009, pqac-00000012) | R77W was historically proposed, but causality has been questioned in later work; no firmly validated pathogenic example variant was provided in gathered evidence (pqac-00000009) | Mechanical friction reported to exacerbate generalized non-inflammatory PSS in a quiz/case context (pqac-00000010) | DOI: 10.1016/j.ygeno.2012.01.005 |
| Generalized inflammatory peeling skin syndrome / PSS type B / PSS1 / peeling skin disease (PSD) | Congenital ichthyosiform erythroderma with lifelong patchy/superficial peeling, severe pruritus, burning red denuded patches with collarette; may show urticaria, angioedema, food allergies, asthma, elevated IgE/eosinophilia; due to corneodesmosomal dysfunction/barrier defect (pqac-00000002, pqac-00000011, pqac-00000012, pqac-00000014) | **CDSN** (corneodesmosin) | Autosomal recessive for peeling skin disease; monoallelic CDSN variants instead can cause autosomal dominant hypotrichosis simplex of the scalp (pqac-00000012) | c.598C>T p.Gln200*; c.164_167dup p.Thr57Profs*6; c.1358G>A missense (pqac-00000012, pqac-00000009) | Summer worsening reported; inflammatory/barrier-driven phenotype rather than classic friction-limited acral disease (pqac-00000009, pqac-00000014) | DOI: 10.1016/j.ajhg.2010.07.005; 10.1038/jid.2010.363; 10.1111/1346-8138.15136; 10.1159/000368823 |
| Generalized ichthyotic peeling skin syndrome due to **FLG2** | Recessive generalized skin-fragility/peeling with ichthyotic features; cleavage in lower stratum corneum, parakeratosis, reduced keratin 2/corneodesmosin/desmocollin-1/desmoglein-1, abnormal keratin compaction (pqac-00000010, pqac-00000008) | **FLG2** | Recessive / biallelic loss-of-function (pqac-00000008, pqac-00000010) | c.632C>G, p.Ser211*; p.Tyr355* also cited in commentary evidence (pqac-00000010, pqac-00000008) | Not specifically stated in gathered evidence | DOI: 10.1016/j.jid.2018.01.038 |
| PLACK syndrome (related PSS phenotype) | Generalized peeling, leukonychia, acral punctate keratoses, cheilitis, knuckle pads; may also show xerosis, palmoplantar keratoderma, hyperkeratotic papules; distinct generalized AR peeling phenotype with impaired keratinocyte adhesion/apoptosis (pqac-00000004, pqac-00000007) | **CAST** (calpastatin) | Autosomal recessive (pqac-00000004, pqac-00000007) | p.Glu441Ter; homozygous exon 18 insertion causing frameshift/premature truncation (pqac-00000004) | Spontaneous or trauma-associated peeling; bullae may follow trauma (pqac-00000004) | PMID: 37317743; DOI: 10.25259/ijdvl_1138_2021; 10.1016/j.ajhg.2014.12.026 |


*Table: This table summarizes the main Peeling Skin Syndrome subtypes and closely related peeling disorders supported by the gathered evidence, including genes, inheritance, representative variants, triggers, and key references. It is useful as a compact crosswalk between clinical classification and molecular etiology.*