Olmsted Syndrome

  • Gene mutations:
    • Transient receptor potential cation channel subfamily V member TRPV3
    • Membrane-bound transcription factor protease site 2; in X-linked recessive type
    • X-chromosome linked lymphocyte regulated
  • More commonly autosomal dominant than recessive with some cases of X-linked recessive inheritance
    Membrane-bound transcription factor protease site 2 mutations:
    Olmsted syndrome
    • Ichthyosis follicularis with atrichia and photophobia syndrome
    • Keratosis follicularis spinulosa decalvans syndrome
  • Altered transient receptor potential cation-channels leads to abnormal epidermal differentiation, hair maturation, inflammatory response, pain, and pruritus pathways
  • Altered membrane-bound transcription factor protease site 2 leads to abnormal zinc metalloprotease production and subsequent aberrant cholesterol homeostasis
  • Well-demarcated diffuse palmoplantar keratoderma, late flexion contractures / digital constriction / autoamputation
  • Painful, pruritic perioral / perianal / intertriginous erythema and warty hyperkeratosis
  • Flexure / extremity linear keratoses
  • X-linked recessive type
    • Alopecia totalis, nail 
  • Oral keratotic plaques, corneal dysplasia, erythromelalgia, deafness, joint laxity
  • Skin infections, squamous cell carcinoma, melanoma

Pathology: 

  • Acanthosis, orthohyperkeratosis, parakeratosis, papillomatosis, perivascular inflammation

Differential:

  • Mal de Meleda
  • Vohwinkel syndrome
  • 3-ketodihydrosphingosine reductase-related erythrokeratoderma 
  • Pachyonychia congenita
  • Acrodermatitis enteropathica
  • Mucocutaneous candidiasis
  • Psoriasis
  • Oral retinoids
  • Excision of hyperkeratosis and skin graft
  • Erlotinib (epidermal growth factor receptor inhibitor)