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.

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.

TO THE EDITOR:The oculo-ectodermal syndrome (OES) is distinguished by the findings of aplasia cutis congenita, non-ossifying fibromas of the long bones, epibulbar dermoids, and areas of skin hyperpigmentation. A total of 15 cases of OES have been reported [Ardinger et al., 2007] since its description by Toriello et al. [1993]. Additional findings such as arachnoid cysts, giant cell granulomas of the jaw, craniofacial lipomas, and eyelid defects are seen in OES. The clinical features of OES overlap with encephalocraniocutaneous lipomatosis which is characterized by cutis aplasia and epibulbar dermoids as well as CNS lipomas and naevus psiliparus [Moog, 2009]. Other syndromes that have features in common with OES include: Adams-Oliver syndrome (aplasia cutis congenita), Goldenhar syndrome (epibulbar dermoids), and Jaffe-Campanacci syndrome (non-ossifying fibromas of the long bones).The genetic etiology of oculo-ectodermal syndrome is unknown; all karyotypes reported thus far have been normal [Martin et al., 2007]. We report an additional case of oculo-ectodermal syndrome that demonstrates mosaicism for a de novo deletion at Xq12 found on comparative genomic hybridization.The patient is a 5-year-old boy referred to Genetics Clinic for evaluation of both Jaffe-Campanacci syndrome and Goldenhar syndrome. He was the 3,720 g (75th centile) 48.2 cm long (10-25th centile) product of an uncomplicated full-term pregnancy to a 29-year-old G 3 P 2 SAb 1 mother. He was born by an unremarkable vaginal delivery. At birth, he was noted to have torticollis, scalp lesions, and ocular dermoids. The scalp lesions were described as resembling blisters. This led to a genetics consultation where he was diagnosed with Goldenhar syndrome.During the first year of life he was noted to have a limb length discrepancy. Radiographs showed non-ossifying fibromas located at the bilateral humeri and left radius and ulna and the bilateral femora and left distal tibia and fibula. Based on this, a diagnosis of Jaffe-Campanacci syndrome was made. In early childhood, he underwent surgical repair of a left-sided inguinal hernia and undescended testicle, two sets of pressure equalization tubes, oral surgery for tooth extraction, the addition of caps and crowns for tooth decay. Shortly after birth he had a ''scalp cyst'' excision but the pathology from this is unknown. We have little additional information about the patient's early childhood but he did not have any hospitalizations or acute medical illnesses.His early motor development was normal: He sat at 6 months, stood at 9 months, and walked at 1 year. Despite walking at 1 year of age the subject was described as ''clumsy,'' which was likely due to his limb length discrepancy. He was recently restricted by his orthopedic physician to under a quarter mile of walking at a time due to his leg length discrepancy. The patient had delayed speech and was in speech therapy by age 2 years. Currently he has attention issues in school.Family history was notable for a sister with tetralogy of Fallot. There were ...

Phenylketonuria (PKU) is an inborn error of metabolism affecting approximately one in every 10,000 infants born in Europe and the USA. Unless treated with a phenylalanine-restricted diet beginning in infancy, PKU can be associated with mental retardation, seizures, eczema and other symptoms. Treatment prevents the most severe consequences of PKU, but compliance with the strict dietary regimen is poor, especially in adolescents and adults. Despite the decline in IQ and increased emotional problems associated with poor adherence to the diet, few novel advances in treatments for PKU have occurred since 1963, when it became the first condition for which newborn screening was available. Sparked in part by acceptance of the policy of lifelong dietary treatment, alternative therapies are being investigated. These include innovations in production of low-protein foods, psychosocial interventions, new medications, enzyme therapy and perhaps even gene therapy in the future.