Xiao-Ping Qi1, Jian-Zhong Peng2, Xiao-Wei Yang3, Zhi-Lie Cao4, Xiu-Hua Yu5, Xu-Dong Fang6, Da-Hong Zhang7, Jian-Qiang Zhao8. 1. X Qi, Department of Urologic and Oncologic Surgery, The 117th PLA Hospital, Hangzhou , 310004, China qxplmd@163.com. 2. J Peng, Dermatology, Hangzhou Third People's Hospital, Hangzhou, China. 3. X Yang, pediatrics, the First People's Hospital of Wenling City, Hangzhou, China. 4. Z Cao, Department of Urologic and Oncologic Surgery, The 117th PLA Hospital, Hangzhou, China. 5. X Yu, Department of Urologic and Oncologic Surgery, The 117th PLA Hospital, Hangzhou , China. 6. X Fang, Department of Urologic and Oncologic Surgery, The 117th PLA Hospital, Hangzhou , China. 7. D Zhang, Urology, People's Hospital of Hangzhou Medical College, Hangzhou, China. 8. J Zhao, Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou , China.
Abstract
BACKGROUND: Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in 'MEN 2A with CLA', one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back. PATIENT FINDINGS: This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harbouring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, 1 presented with MTC and pheochromocytoma, 9 with MTC only, 2 with elevated serum calcitonin, and 3 younger subjects with normal serum calcitonin levels. This family's clinical data revealed a later diagnosis of MTC (mean age, 45.9 [range: 23-73] years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family. SUMMARY AND CONCLUSIONS: This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype-phenotype spectrum in MEN 2A.
BACKGROUND: Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in 'MEN 2A with CLA', one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back. PATIENT FINDINGS: This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harbouring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, 1 presented with MTC and pheochromocytoma, 9 with MTC only, 2 with elevated serum calcitonin, and 3 younger subjects with normal serum calcitonin levels. This family's clinical data revealed a later diagnosis of MTC (mean age, 45.9 [range: 23-73] years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family. SUMMARY AND CONCLUSIONS: This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype-phenotype spectrum in MEN 2A.
Authors: Samuel A Wells; Sylvia L Asa; Henning Dralle; Rossella Elisei; Douglas B Evans; Robert F Gagel; Nancy Lee; Andreas Machens; Jeffrey F Moley; Furio Pacini; Friedhelm Raue; Karin Frank-Raue; Bruce Robinson; M Sara Rosenthal; Massimo Santoro; Martin Schlumberger; Manisha Shah; Steven G Waguespack Journal: Thyroid Date: 2015-06 Impact factor: 6.568
Authors: R M Hofstra; R H Sijmons; T Stelwagen; R P Stulp; B G Kousseff; C J Lips; P M Steijlen; P C Van Voorst Vader; C H Buys Journal: J Invest Dermatol Date: 1996-08 Impact factor: 8.551