Question: A 56-year-old woman with a history of oral papillomas since her early teens presented with heartburn and progressive dysphagia to solids. Additional history included streaky erythematous lesions of the extremities, papillomas in the axilla and inguinal region, and tooth loss. Physical examination revealed linear erythematous reddish streaks on her legs with thinning of the skin (Figure A). She had old scars from removal of papillomas in the axilla, syndactyly, and split fingernails. Oral examination revealed scars from prior cryotherapy for oral papillomas. An upper endoscopy revealed numerous (>100) polypoid lesions in the distal 9-cm of the esophagus (Figure B). Biopsies were consistent with squamous papilloma without dysplasia, and in situ hybridization testing for human papilloma virus was negative. What is the diagnosis? Look on page 1111 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Focal dermal hypoplasia or Goltz syndrome is a rare genodermatosis characterized by multiple abnormalities of ectodermal and mesodermal structures. The underlying abnormality is a mutation in the PORCN gene on the X chromosome, which can be inherited or occur de novo, in which case symptoms are usually milder.1Grzeschik K.H. Bornjoldt D. Oeffner F. et al.Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia.Nat Genet. 2007; 39: 833-835Crossref PubMed Scopus (223) Google Scholar Males often die in utero and the disorder is predominantly seen in females. The manifestations vary among affected individuals and many have only a subset of the characteristic features. Patients can present with ocular, otologic, skeletal, genitourinary, cutaneous, or gastrointestinal manifestations. The characteristic skin manifestation, as seen in our patient, includes linear and reticular areas of hypo- and hyperpigmentation. Limb malformations include syndactyly (partial or total webbing of digits). Mucocutaneous verrucoid papillomas are a common finding and are most commonly seen around the mouth and nose. Rarer presentations include esophageal papillomatosis.2Brinson R.R. Schuman B.M. Mills L.R. et al.Multiple squamous papillomas of the esophagus associated with Goltz syndrome.Am J Gastroenterol. 1987; 82: 1177-1179PubMed Google Scholar Esophageal papillomatosis is a rare condition. Common symptoms include heartburn and progressive dysphagia. Because the papillomas in focal dermal hyperplasia are not premalignant, squamous papillomas of the esophagus can, and should, be managed conservatively, unless there is frank obstruction. However, because the endoscopic appearance can be confused with verrucous squamous cell carcinoma, biopsies should be done to exclude this diagnosis, along with testing for human papilloma virus.2Brinson R.R. Schuman B.M. Mills L.R. et al.Multiple squamous papillomas of the esophagus associated with Goltz syndrome.Am J Gastroenterol. 1987; 82: 1177-1179PubMed Google Scholar Our patient was started on a proton pump inhibitor for gastroesophageal reflux and, subsequently, had near resolution of heartburn symptoms and dysphagia. Genetic testing for the PORCN gene mutation on peripheral blood was negative, suggesting that she represents a somatic mosaic for the de novo mutation in the PORCN gene. Approximately 95% of females with focal dermal hypoplasia have a new gene mutation and the presence of a somatic mosaic for the de novo PORCN gene mutation could explain the relatively mild phenotypic expression of the disease in our patient.3Wechsler M.A. Papa C.M. Haberman F. et al.Variable expression in focal dermal hypoplasia An example of differential X-chromosome inactivation.Am J Dis Child. 1988; 142: 297-300Crossref PubMed Scopus (35) Google Scholar