Adults with Sotos syndrome: review of 21 adults with molecularly confirmed NSD1 alterations, including a detailed case report of the oldest person.

Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities. The diagnosis of Sotos syndrome relied solely on these clinical criteria until haploinsufficiency of the NSD1 gene was identified as causative. We describe a 63-year-old woman with classic features and a pathogenic NSD1 mutation, who we believe to be the oldest reported person with Sotos syndrome. She is notable for the diagnosis of Sotos syndrome late in life, mild cognitive limitation, and chronic kidney disease attributed to fibromuscular dysplasia for which she recently received a transplant. She has basal cell and squamous cell carcinoma for which her lifetime of sun exposure and fair cutaneous phototype are viewed as risk factors. We also reviewed previous literature reports (n = 11) for adults with Sotos syndrome, and studied patients ascertained in the Spanish Overgrowth Syndrome Registry (n = 15). Analysis was limited to 21/27 (78%) total patients who had molecular confirmation of Sotos syndrome (15 with a mutation, 6 with a microdeletion). With a mean age of 26 years, the most common features were learning disabilities (90%), scoliosis (52%), eye problems (43%), psychiatric issues (30%), and brain imaging anomalies (28%). Learning disabilities were more severe in patients with a microdeletion than in those with a point mutation. From this small study with heterogeneous ascertainment we suggest modest adjustments to the general healthcare monitoring of individuals with Sotos syndrome. Although this series includes neoplasia in four cases, this should not be interpreted as incidence. Age-appropriate cancer surveillance should be maintained.

Health-care referrals from direct-to-consumer genetic testing.

BACKGROUND: direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. AIM: to query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. METHODS: invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. RESULTS: the invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT. Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be "clinically useful." BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. CONCLUSIONS: this clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system.