MON-333 Cutaneous Skeletal Hypophosphatemic Syndrome (Cshs) Caused by Somatic HRAS p.G13R Mutation: Long Follow-Up of Two Brazilian Women

Media type: E-Article

Title: MON-333 Cutaneous Skeletal Hypophosphatemic Syndrome (Cshs) Caused by Somatic HRAS p.G13R Mutation: Long Follow-Up of Two Brazilian Women

Contributor: Maia, Thamiris Freitas; Freire, Bruna Lucheze; Rodrigues, Andresa de Santi; Jorgetti, Vanda; Rocha, André Caroli; Moises, Caio Santiago; de Souza, Bruno Ferraz; Rodrigues, Marcelo Bordalo; Jorge, Alexander Augusto de Lima; Martin, Regina Matsunaga; Cabral, Hially R

imprint: The Endocrine Society, 2020

Language: English

DOI: 10.1210/jendso/bvaa046.1383

ISSN: 2472-1972

Keywords: Endocrinology, Diabetes and Metabolism

Origination:

Footnote:

Description: Abstract BACKGROUND CSHS refers to the association of epidermal nevus syndrome (ENS), skeletal dysplasia, and hypophosphatemic osteomalacia (OM) mediated by FGF23 resulting from post zygotic mutations in RAS signaling pathway, with known by relationship with human cancers. CLINICAL CASE Patient 1 presented ENS since birth at right hemibody. At 1.6-yr-old, she underwent treatment for a left inguinal rhabdomyosarcoma. At 3-yr-old, she had an atraumatic right femur fracture associated with muscle weakness, and laboratory data and X-rays suggesting OM. Phosphate and calcitriol were initiated, but with poor adherence, and no improvement; skeletal deformities got worse and the girl became wheelchair user at 13-yr-old. Skeletal CT scan at age 17 showed dysplastic lesions with lytic changes at right dimidium (skull, jaw, ribs, pelvis and femur) with systemic OM signs confirmed by bone biopsy. The progressive enlargement of the jaw lesion required surgical removal after 2 years; histopathology revealed giant cell tumor. Patient 2 also had congenital ENS on the right dimidium with complaint of bone pain and muscle weakness since 2-yr-old. She evolved with bone fractures and deformities at 4-yr-old, becoming wheelchair user after 2 years. Iliac crest biopsy confirmed OM, already suspected based on laboratorial and X-rays findings at age 7. She had few improvements with phosphate and calcitriol treatment also due to low compliance. During follow-up, symptomatic nephrolithiasis occurred and, in regions affected by EN, multiple basal cell carcinomas (BCCs) emerged requiring excisions. Skeletal CT scan at age 36 showed dysplastic lesions at right hemibody (skull, ribs, pelvis, and limbs) with diffuse bone rarefaction and signs of OM. Sanger sequencing of DNA from EN and jaw tumor samples of patient 1 and from EN and BCC samples of patient 2 disclosed heterozygous HRAS p.G13R mutation, and this mutation was absent in leukocytes DNA from both patients confirming CSHS mosaicism. Owing to the CSHS associated increase risk of cancer, screening with thyroid and breast ultrasound, mammography, CT of skull, chest, abdomen, and pelvis ruled out presence of tumors in patient 1. Patient 2 is waiting for similar screening. Nowadays, patient 1 is 25-yr-old and patient 2 is 36-yr-old; both women have maintenance of OM, characterized by persistent hypophosphatemia with elevated bone formation makers despite treatment with phosphate and calcitriol. CONCLUSION CHSC is a very rare syndrome with less than 10 cases with molecular characterization in literature. Although Collins et al suggest an age-dependent improvement in mineral abnormalities, we reported two women without OM recovery probably because of extensive bone dysplasia. These cases also reinforce association of CSHS with neoplasms, including first descriptions of patients with rhabdomyosarcoma and giant cell tumor of jaw and the longest follow-ups described until.

Access State: Open Access

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