Focal dermal hypoplasia, also known as Goltz syndrome, is a rare X-linked dominant disorder caused by a mutation in the PORCN gene located on the X chromosome (p11.23).13,14PORCN encodes the human homolog of Drosophila melanogaster porcupine, an endoplasmic reticulum protein involved in the processing of proteins of the Wingless-related integration site or Wnt signaling pathway. This pathway is critical in the embryonic development of mesoectodermal structures including skin, craniofacial and long bones, eyes, and teeth. Hence, the dysregulation of this pathway results in a wide array of multisystemic manifestations involving the skin (reticular hyperpigmentation or hypopigmentation, atrophy, telangiectasias, and papillomas), skeleton (syndactyly, ectrodactyly, hypoplasia or aplasia of truncal skeleton), eyes (coloboma, microphthalmia), mucous membranes (raspberry papillomas), and teeth (small, malformed, or absent teeth).15–18 There are approximately 300 cases of Goltz syndrome reported to date worldwide, and the majority are women (90%) because the disease carries a high rate of in utero lethality in males.19
Although mucocutaneous papillomas involving the mouth, nose, larynx, vagina, and rectum were observed in 45%–65% of the cases, esophageal papillomas seem to be particularly infrequent.20,21 Per literature review, there are only 5 cases of esophageal papillomas associated with Goltz syndrome.12,22–25 Similar to our patient, all previously reported cases had a degree of dysphagia requiring endoscopic therapy. However, all cases had squamous papillomas without dysplasia, in contrast to our patient who was found to have ESCC. Hence, papillomatosis associated with Goltz syndrome has been considered nonmalignant, and there are no recommendations for surveillance. Given the fact that ESCC occurs mostly in the upper and middle one-third of esophagus vs EAC in the distal one-third and the GE junction, this occurrence of ESCC in an atypical location in a young woman without traditional risk factors is suggestive of malignant transformation of underlying papillomatosis. Our case shows that papillomas associated with Goltz syndrome could have malignant potential and therefore are worthy of surveillance. To our knowledge, this is the first reported case of esophageal cancer associated with Goltz syndrome.
Author contributions: M. Hafiz wrote the manuscript, and is the article guarantor. S. Sundaram, AR Naqash, and P. Walker wrote the manuscript. J. Speicher and N. Talaat edited the article. A. Sutton conducted histopathological analysis and contributed pathology images.
Financial disclosure: None to report.
Previous presentation: The case report was presented at World Congress of Gastroenterology at ACG2017; October 13–18, 2017; Orlando, FL.
Informed consent was obtained for this case report.
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