====== Goltz Syndrome ======
====Main Features====

X-linked dominant multisystem ecto-mesodermal dysplasia affecting skin, skeleton, eyes, teeth, and face; ~90% of patients are female (M:F ~1:9), with hemizygous variants usually lethal in utero
  * Blaschkolinear dermal hypoplasia (atrophic, erythematous, or translucent streaks) present at birth, often with congenital patchy skin aplasia (aplasia cutis)
  * Soft yellow-pink nodular fat herniation into the dermis (60-70%) and telangiectasias (~80%)
  * Blaschkolinear hyper- and hypopigmentation
  * Periorificial and mucosal papillomas (perinasal, perioral, perianal, genital, laryngeal, esophageal) developing after infancy; may cause dysphagia or airway obstruction
  * Ridged or dystrophic nails, micronychia; sparse brittle hair, patchy alopecia
  * Limb malformations in >50%: ectrodactyly ("lobster claw"), oligodactyly, syndactyly, polydactyly, split hand/foot, transverse and long-bone reduction defects
  * Osteopathia striata on long-bone metaphyseal radiographs: asymptomatic, but a useful diagnostic clue in mild cases
  * Proposed clinical criteria: at least 3 characteristic skin findings (patchy skin aplasia, nodular fat herniation, Blaschkolinear pigmentary change, telangiectasia, ridged dysplastic nails) plus at least 1 characteristic limb malformation

====Eye Findings====

Ocular anomalies in ~15% (older series 20-40%), typically asymmetric, ranging from cosmetic to blinding
  * Microphthalmia (most common) and anophthalmia
  * Iris and chorioretinal coloboma; retinal and optic nerve dysplasia
  * Lacrimal and nasolacrimal duct abnormalities
  * Strabismus, cataract, corneal and anterior chamber defects
  * Eyelid and conjunctival papillomas, ectropion, ptosis, sparse eyelashes and eyebrows

====Other Findings====
  * Craniofacial: pointed chin, facial asymmetry, midface/maxillary hypoplasia, notched alae nasi, small or protruding ears, thin notched upper lip
  * Dental (20-50%): enamel hypoplasia, vertical grooving, hypodontia/oligodontia, irregular crowns, delayed eruption, malocclusion
  * Ears and hearing: microtia, aural atresia, conductive and sensorineural hearing loss, vestibulocochlear dysplasia
  * Central nervous system: intelligence usually normal, but intellectual disability, speech delay, microcephaly, and structural brain anomalies occur
  * Growth: short stature and growth failure; growth hormone deficiency investigated as a contributor
  * Renal: fused or duplex kidney, renal hypoplasia, cysts
  * Gastrointestinal and abdominal wall: omphalocele, midline thoracoabdominal wall defects (overlap with pentalogy of Cantrell and limb-body wall complex)
  * Rare: giant cell tumor of bone, supernumerary nipple, athelia
  * Histopathology: atrophic dermis with adipocytes abutting the epidermis or clustered in reticular dermis, dilated papillary dermal vessels, sparse disorganized collagen</em>

====Etiology====

  * X-linked dominant inheritance; ~95% of cases in females are de novo, ~5% inherited
    * Loss-of-function pathogenic variants in PORCN (Xp11.23), encoding porcupine O-acyltransferase, which palmitoylates Wnt proteins for secretion; disrupted Wnt/beta-catenin signaling impairs ecto-mesodermal development
  * Male survivors result from postzygotic somatic mosaicism or 47,XXY (Klinefelter syndrome)
  * Phenotypic variability reflects random X-inactivation (functional mosaicism) and postzygotic mosaicism; no genotype-phenotype correlation established
  * Point and small mutations predominate in sporadic cases, larger deletions in familial cases; germline mosaicism reported
  * Blood DNA testing may be negative in mosaic patients; testing DNA from affected skin or fibroblasts improves diagnostic yield

====References====
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Phenotypes%2C+Genetics%2C+and+Estimated+Prevalence+of+Focal+Dermal+Hypoplasia+Goltz+Syndrome|Herlin LK, et al. Phenotypes, Genetics, and Estimated Prevalence of Focal Dermal Hypoplasia (Goltz Syndrome): A Single-Center Report. Pediatr Dermatol. 2024]]
  * [[https://medlineplus.gov/genetics/condition/focal-dermal-hypoplasia/|MedlinePlus Genetics. Focal dermal hypoplasia. National Library of Medicine]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Erosions+and+vesicles+following+the+lines+of+Blaschko+in+a+neonate|Escudero-Gongora MDM, et al. Erosions and Vesicles Following the Lines of Blaschko in a Neonate. Pediatr Dermatol. 2018]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Laser-Induced+Neocollagenesis+in+Focal+Dermal+Hypoplasia+Associated+With+Goltz+Syndrome|Krakowski AC, et al. Laser-Induced Neocollagenesis in Focal Dermal Hypoplasia Associated With Goltz Syndrome in a Girl. JAMA Dermatol. 2017]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Angioma-serpiginosum-like+and+hyperkeratotic+lesions+in+a+patient+with+Goltz+syndrome|Fernandez-Flores A, et al. Angioma-Serpiginosum-Like and Hyperkeratotic Lesions in a Patient With Goltz Syndrome. J Cutan Pathol. 2022]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Revisiting+histopathologic+findings+in+Goltz+syndrome|Ko CJ, et al. Revisiting Histopathologic Findings in Goltz Syndrome. J Cutan Pathol. 2016]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Focal+dermal+hypoplasia+updates+Wang+Oral+Diseases|Wang L, et al. Focal Dermal Hypoplasia: Updates. Oral Dis. 2014]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Growth+failure+in+focal+dermal+hypoplasia|Hsu SC, et al. Growth Failure in Focal Dermal Hypoplasia. Am J Med Genet A. 2019]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Phenotype+and+genotype+in+17+patients+with+Goltz-Gorlin+syndrome|Maas SM, et al. Phenotype and Genotype in 17 Patients With Goltz-Gorlin Syndrome. J Med Genet. 2009]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=PORCN+gene+mutations+and+the+protean+nature+of+focal+dermal+hypoplasia|Clements SE, et al. PORCN Gene Mutations and the Protean Nature of Focal Dermal Hypoplasia. Br J Dermatol. 2009]]
  * [[https://pubmed.ncbi.nlm.nih.gov/?term=Mosaicism+due+to+postzygotic+mutations+in+women+with+focal+dermal+hypoplasia|Heinz L, et al. Mosaicism Due to Postzygotic Mutations in Women With Focal Dermal Hypoplasia. Br J Dermatol. 2019]]

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