0000000000037978
AUTHOR
Daniela Giachino
Response to Stanich et al.: Correspondence regarding-PTEN hamartoma tumor syndromes in childhood-Description of two cases and a proposal for follow-up protocol
The follow-up protocol, which we describe in this study can serve as a practical proposal for clinicians, and as a basis for future studies. We strongly urge the clinician to start an early surveillance of the gastrointestinal tract including regular endoscopy. The main management goals in PHTS patients are to detect colon cancer early, and to prevent polyp-related complications (bowel obstruction from intussusception). The presence of multiple nonmalignant polyps in patients with PTEN mutations may complicate noninvasive methods of colon evaluation [Tan et al., 2012]. In addition, there is a high variability in severity of polyps progression, and the malignant potential of these lesions is…
Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility
Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as p…
PTEN hamartoma tumor syndromes in childhood: description of two cases and a proposal for follow-up protocol
PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germ-line mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders, Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, are allelic conditions. Because PTEN mutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within the PTEN gene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, end…