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The PTEN hamartoma tumor syndrome, manifestations of which include Cowden disease and Bannayan-Riley-Ruvalcaba syndrome, is caused by various mutations of the PTEN gene located at 10q23. Its major criteria are macrocephaly and a propensity to develop breast and thyroid cancers as well as endometrial carcinoma. Minor diagnostic criteria include hamartomatous intestinal polyps, lipomas, fibrocystic disease of the breasts, and fibromas. mutations of PTEN can also be found in patients with Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum). The authors report the case of a 17-year-old girl who had a severe cyanotic cardiac malformation for which surgery was not advised and a heterozygous missense mutation (c.406T>C) in exon 5 of PTEN resulting in the substitution of cysteine for arginine (p.Cysl36Arg) in the protein, which was also found in her mother and sister. The patient presented in the pediatric emergency department with severe spastic paraparesis. A magnetic resonance imaging study of the spine showed vertebral hemangiomas at multiple levels, but stenosis and compression were maximal at level T5-6. An emergency T5-6 laminectomy was performed. The decompression was extremely hemorrhagic because the rapid onset of paraparesis necessitated prompt treatment, and there was no time to perform preoperative embolization. The patient's postoperative course was uneventful with gradual recovery. This represents the first report of an association of a PTEN mutation and multiple vertebral angiomas. The authors did not treat the remaining angiomas because surgical treatment was contraindicated without previous embolization, which in itself would present considerable risk in this patient with congenital cyanotic heart disease.

CONTEXT: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline-inactivating mutations of the PTEN tumor suppressor gene. Carriers develop benign and malignant tumors of multiple tissues, including the breast, thyroid, intestine, and skin. Surveillance to facilitate the early detection and treatment of malignancies is recommended but,because thyroid cancers have been reported almost exclusively in adults, childhood risk is considered to be low, and consensus guidelines recommend that surveillance imaging begin at 18 yr of age. OBJECTIVE/PATIENTS: Seven children with PHTS referred to two thyroidologists form the basis of this report. Medicalrecords, operative histology, and PTEN mutational analysis were reviewed to evaluate the pediatric presentation of PHTS-associated thyroid neoplasia. RESULTS: Five of the seven children presented with thyroid nodules or thyroid cancer between the ages of 6 and 12 yr, often as the initially identified component of their PHTS. Two others were diagnosed with PHTS on the basis of extrathyroidal features but had markedly abnormal screening ultrasounds with solid thyroid nodule(s) of at least 2 cm, despite the documentation of normal physical examinations. Five of the seven children in this cohort developed thyroid cancer. CONCLUSIONS: Patients with PHTS can develop thyroid nodules and thyroid cancer in early childhood. This argues both for a high index of suspicion for PHTS in children diagnosed with multiple thyroid nodules and for careful thyroid surveillance in children diagnosed with PHTS. Because early detection improves the outcome of thyroid cancer, we recommend ultrasound surveillance forall patients upon the confirmation of a germline PTEN mutation, regardless of their age.