ESPE Abstracts (2018) 89 P-P2-407

Bannayan-Riley-Ruvalcaba Syndrome with PTEN Mutation in a Patient Affected by Congenital Hypothyroidism due to TPO Gene Alteration

Gaia Vincenzia, Maria Cristina Vigonea, Elena Peronia, Luca Saraccoa, Pier Luigi Paesanob, Riccardo Maggiorec, Gilberto Maric, Maria Grazia Patricellid & Giovanna Webere


aVita-Salute San Raffaele University, IRCSS San Raffele, Department of Pediatrics, Milan, Italy; bVita-Salute San Raffaele University, IRCSS San Raffele, Department of Radiology, Milan, Italy; cVita-Salute San Raffaele University, IRCSS San Raffele, Department of Endocrine Surgery, Milan, Italy; dVita-Salute San Raffaele University, IRCSS San Raffele, Medical Genetics Unit, Milan, Italy; eVita-Salute San Raffaele University, IRCSS San Raffele, Department of Pediatrics, Milan, Italy


We present the case of a 7-year-old female affected by permanent congenital hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome. The patient was born at 31+4 gestational weeks because of premature rupture of membranes. At birth her auxological parameters were adequate for gestational age with a 75th percentile head circumference. She was diagnosed with congenital hypothyroidsm (TSH 1016 mcu/ml, FT4 <0.4 ng/dl) with an in situ gland caused by a homozygous mutation of the TPO gene (ins.GGCC395, exon 8). This variation was inherited from both parents: the mother suffered from non-autoimmune hypothyroidism and celiac disease and the father had normal thyroid function. Physical examinations, thyroid function tests, and ultrasounds of the neck were regularly performed. Beginning at 7 months of age, facial abnormalities such as frontal bossing and hyperthelorism were observed, as well as an increasing head circumference (>97° percentile). The patient also presented with a mild delay in neuromotor development (first steps at 18 months, first words at 24 months). The first brain MRI preformed showed no alterations. At 2 and a half years old, a dorsal and a periumbilical lipoma were observed and subsequently surgically removed. At 6 years old, a thyroid ultrasound revealed for the first time five nodules in the right lobe and four in the left one and a brain MRI identified a suspected orbital hemangioma. After genetic counselling, the sequencing analysis of PTEN gene was performed showing the presence of a heterozygous mutation (c.635-1G>C) coding for a truncated protein causing Bannayan-Riley-Ruvalcaba syndrome (BRRs). In consideration of the increased risk of developing thyroid cancer, the patient recently underwent total thyroidectomy: 21 adenomatous nodules were described at the histological exam. In 8/8 nodules, the immunohistochemical analysis revealed a loss of nuclear expression of PTEN. The clinical features of our patient (face abnormalities, macrocephaly, subcutaneous lipomas, hemangiomas, and multinodular goiter) represent some of the several phenotypic expressions of BRRs. Mutations in the tumor suppressor gene PTEN cause an increased oncologic risk thus prophylactic total thyroidectomy should be considered in selected patients.