Automated syndrome diagnosis by three-dimensional facial imaging.

PURPOSE: Deep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face is affected in 30-40% of known genetic syndromes. Here, we determine whether syndromes can be diagnosed from 3D images of human faces. METHODS: We analyzed variation in three-dimensional (3D) facial images of 7057 subjects: 3327 with 396 different syndromes, 727 of their relatives, and 3003 unrelated, unaffected subjects. We developed and tested machine learning and parametric approaches to automated syndrome diagnosis using 3D facial images. RESULTS: Unrelated, unaffected subjects were correctly classified with 96% accuracy. Considering both syndromic and unrelated, unaffected subjects together, balanced accuracy was 73% and mean sensitivity 49%. Excluding unrelated, unaffected subjects substantially improved both balanced accuracy (78.1%) and sensitivity (56.9%) of syndrome diagnosis. The best predictors of classification accuracy were phenotypic severity and facial distinctiveness of syndromes. Surprisingly, unaffected relatives of syndromic subjects were frequently classified as syndromic, often to the syndrome of their affected relative. CONCLUSION: Deep phenotyping by quantitative 3D facial imaging has considerable potential to facilitate syndrome diagnosis. Furthermore, 3D facial imaging of "unaffected" relatives may identify unrecognized cases or may reveal novel examples of semidominant inheritance.

Use of Transition Resources by Primary Care Providers for Youth With Intellectual and Developmental Disabilities.

Youth with intellectual and developmental disabilities (IDD) often experience difficulties with successful transition from pediatric to adult healthcare. A consultative Transition Clinic for youth with IDD was piloted as a quality improvement project, and assessed the engagement of primary care providers (PCPs) for transition planning after patients were seen in clinic. Although many PCPs found the clinic and resources useful, individual and systemic barriers often prohibited them from participating in transition planning for this patient population. These findings highlight systemic barriers that need to be addressed to ensure successful transition, as well as the need for a specialized Transition Clinic with involvement of specialists with expertise in IDD, such as Developmental-Behavioral Pediatrics, to assist throughout transition process.

Understanding the Viscosity of Liquids used in Infant Dysphagia Management.

When assessing swallowing in infants, it is critical to have confidence that the liquids presented during the swallow study closely replicate the viscosity of liquids in the infant's typical diet. However, we lack research on rheological properties of frequently used infant formulas or breastmilk, and various forms of barium contrast media used in swallow studies. The aim of the current study was to provide objective viscosity measurements for typical infant liquid diet options and barium contrast media. A TA-Instruments AR2000 Advanced Rheometer was used to measure the viscosity of five standard infant formulas, three barium products, and two breastmilk samples. Additionally, this study measured the viscosity of infant formulas and breastmilk when mixed with powdered barium contrast in a 20 % weight-to-volume (w/v) concentration. The study findings determined that standard infant formulas and the two breastmilk samples had low viscosities, at the lower end of the National Dysphagia Diet (NDD) thin liquid range. Two specialty formulas tested had much thicker viscosities, close to the lower boundary of the NDD nectar-thick liquid range. The study showed differences in viscosity between 60 % w/v barium products (Liquid E-Z-Paque(®) and E-Z-Paque(®) powder); the powdered product had a much lower viscosity, despite identical barium concentration. When E-Z-Paque(®) powdered barium was mixed in a 20 % w/v concentration using water, standard infant formulas, or breastmilk, the resulting viscosities were at the lower end of the NDD thin range and only slightly thicker than the non-barium comparator liquids. When E-Z-Paque(®) powdered barium was mixed in a 20 % w/v concentration with the two thicker specialty formulas (Enfamil AR 20 and 24 kcal), unexpected alterations in their original viscosity occurred. These findings highlight the clinical importance of objective measures of viscosity as well as objective data on how infant formulas or breastmilk may change in consistency when mixed with barium.

Integrating primary care and behavioral health with four special populations: Children with special needs, people with serious mental illness, refugees, and deaf people.

Special patient populations can present unique opportunities and challenges to integrating primary care and behavioral health services. This article focuses on four special populations: children with special needs, persons with severe and persistent mental illness, refugees, and deaf people who communicate via sign language. The current state of primary care and behavioral health collaboration regarding each of these four populations is examined via Doherty, McDaniel, and Baird's (1996) five-level collaboration model. The section on children with special needs offers contrasting case studies that highlight the consequences of effective versus ineffective service integration. The challenges and potential benefits of service integration for the severely mentally ill are examined via description of PRICARe (Promoting Resources for Integrated Care and Recovery), a model program in Colorado. The discussion regarding a refugee population focuses on service integration needs and emerging collaborative models as well as ways in which refugee mental health research can be improved. The section on deaf individuals examines how sign language users are typically marginalized in health care settings and offers suggestions for improving the health care experiences and outcomes of deaf persons. A well-integrated model program for deaf persons in Austria is described. All four of these special populations will benefit from further integration of primary care and mental health services.

Revisiting recombinant 8 syndrome.

Recombinant 8 syndrome, also known as San Luis Valley syndrome, is a rare but important cause for developmental delay and chronic illness noted among individuals of Hispanic ancestry that occurs with greater reported frequency in the Southwest United States. The recombinant chromosome is rec(8)dup(8q)inv(8)(p23.1q22.1) and in all known cases is derived by a parental pericentric inversion, inv(8)(p23.1q22.1). To test our hypothesis that modern medical management strategies may alter the outcome of patients with recombinant 8 syndrome in regard to mortality, morbidity, and neurodevelopmental outcomes, we sought to update the natural history of recombinant 8 syndrome by completing a thorough medical and psychological assessment of affected individuals. Twelve affected individuals, ranging from 2 to 21 years of age, were recruited with IRB approval. Our patients scored on in the mild to severe cognitive functioning level (range 30-70), with surprising preservation in the social/adaptive arenas. Most patients responded well to heart surgery and developmental outcomes were in proportion to cardiac status. Orthopedic surgery to ameliorate effects of spasticity can be complicated by long recovery times and decreased ability to ambulate. Our findings do not support additional morbidly during cardiac repair. Taken together, our findings support a consistent phenotype with improved survival in comparison to previously published studies. Efforts to encourage learning and developmental progress should not be withheld as quality of life for many of these individuals is considered good by their families and medical providers.

Autistic spectrum disorder in a 9-year-old girl with macrocephaly.

CASE: A 9-year-old girl was brought for consultation due to autism and a large head circumference. Her birth weight was 6 pounds after a 37-week gestation to a healthy G3P1SAb 2 mother. She had been a healthy child with the exception of the development of a lipomatous lesion on the left thigh, requiring surgical removal at age 3(1/2) years. Autism was diagnosed at age 5 yr by a developmental pediatrician. She did not have cognitive disabilities or a history of seizures. The family history was notable for maternal infertility with no history of developmental disabilities, large body or head size, or malignancy in close relatives.On physical examination, she was a mildly obese girl with a large head. Her weight was 50.4 kg (>95%), height was 142 cm (90%), and head circumference was 60.3 cm (significantly >95%; 4SDs above the mean). Examination of her skin was notable for a 2 x 6 cm scar on her left thigh and three café au lait macules on her trunk. She was Tanner Stage I. Mild hypotonia with normal deep tendon reflexes was observed; the remainder of the neurological examination was normal.Laboratory studies included high-resolution chromosomes, fragile X, metabolic screens, and methylation for Prader Willie Syndrome and Angelman Syndrome; all these studies were normal. Molecular testing of the PTEN gene (phosphatase and tensin homolog protein) revealed a R355X mutation, consistent with the diagnosis of Bannayan-Riley-Ruvalcaba Syndrome (BRRS). In parents and siblings, PTEN test results were negative for mutations.Endocrine evaluation revealed an abnormal thyroid nodule on ultrasound. Computed tomography and positron emission tomography scans raised suspicion of malignancy. She underwent a total thyroidectomy; the pathology report revealed a thyroid adenoma with Hurthle cells. She was treated with thyroid hormone replacement therapy.