Other

Epidemiology

  • Rare

Pathogenesis

  • Mosaic mutations in various genes depending on clinical phenotype involving keratins, RAS and AKT pathway, FGFRs, etc.

Clinical features

  • Clinical presentation resembles that of the original disease, but follows the lines of Blashko. The chance of extracutaneous disease is higher when extensive skin lesions are seen (earlier mutation).

Diagnosis/pathology

  • Pathology is variable
Epidemiology

  • Rare

Pathogenesis

  • Multiple underlying mosaic mutations, often same mutations as above but more severe phenotypes.

Clinical features

  • Overgrowth syndromes:
    • Proteus (AKT1 gene)
    • SOLAMEN (type 2 mosaicism)
    • CLOVE (PIK3CA)
  • Neavus sebaeceous syndrome (Schimmelpenning) (HRAS)
  • Comedonal (FGFR2)

Pathogenesis

  • NSDHL mutation: 3β-hydroxysteroid dehydrogenase (cholesterol biosynthesis)
  • XLD enopamil binding protein (EBP) gene mutation

Clinical features

  • Unilateral skeletal hypoplasia
  • Unilaterally distributed erythematous, thickened skin and yellowish scale

Treatment:

  • Topical lovastatin or simvastatin plus cholesterol
  •  

Pathogenesis

  • HCCS mutation: mitochondrial holocytochrome c synthase (oxidative phosphorylation and apoptosis)
  • XLD enopamil binding protein (EBP) gene mutation

Clinical features

  • Microphthalmia, dermal aplasia, sclerocornea ± cardiac arrhythmias

Pathogenesis

  • OFD1 (CXORF5) mutation: centrosomal protein at the base of primary (non-motile) cilia (signaling pathways)
  • XLD enopamil binding protein (EBP) gene mutation

Clinical features

  •  Cleft (or pseudocleft) lip/palate, tongue lobulations/hamartomas, hypertrophic oral frenula, digital malformations, CNS abnormalities, facial milia, patchy alopecia

Pathogenesis

  • GNAS: increased signaling in pathways where cyclic AMP acts as a “second messenger”

Clinical features

  • Increased pigmentation due to stimulation of tyrosinase
  • Large blocks of café-au-lait + polyostotic fibrous dysplasia + endocrine hyperfunction (precocious puberty)