Survey of family history taking and genetic testing in pediatric practice.

Family health history collection and genetic testing are core elements for the successful translation of genomics into primary care practice. Yet, little is known about how pediatric providers implement these elements in practice. We surveyed the membership of the American Academy of Pediatrics regarding family health history (FHH) collection and genetic testing in the primary care setting.

Beyond the Genetic Diagnosis: Providing Parents What They Want to Know.

Clinicians need to provide accurate, up-to-date, and balanced information to parents following a prenatal or postnatal diagnosis of Down syndrome and other genetic conditions. Families want information about the genomic outcomes and medical issues, but they also want information about life outcomes and social supports. Because the anticipated outcomes of a condition can change significantly based on available social support, health care, and services, it is important for clinicians to stay up-to-date about new developments and credible, medically reviewed information about Down syndrome and other genetic conditions to access resources for clinical care.

The SSV Evaluation System: A Tool to Prioritize Short Structural Variants for Studies of Possible Regulatory and Causal Variants.

Short structural variants (SSVs) are short genomic variants (<50 bp) other than SNPs. It has been suggested that SSVs contribute to many human complex traits. However, high-throughput analysis of SSVs presents numerous technical challenges.

A cytosine-thymine (CT)-rich haplotype in intron 4 of SNCA confers risk for Lewy body pathology in Alzheimer's disease and affects SNCA expression.

Introduction: We recently showed that tagging single-nucleotide polymorphisms across the SNCA locus were significantly associated with increased risk for Lewy body (LB) pathology in Alzheimer's disease (AD) cases. However, the actual genetic variant(s) that underlie the observed associations remain elusive.

Methods: We used a bioinformatics algorithm to catalog structural variants in a region of SNCA intron 4, followed by phased sequencing.

African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles.

Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE ε4) allele frequency in African-Americans, but yet an increased age-related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of Outer Mitochondria Membrane) and APOE depends on accurate TOMM40'523-APOE haplotypes.

Methods: We have compared the APOE and TOMM40'523 phased haplotype frequencies of a 9.

Surveying the current landscape of clinical genetics residency training.

Purpose: Further knowledge about medical genetics residency training structure and function could help advance this educational process.

Methods: Medical genetics residency program directors were surveyed about their trainees' backgrounds and skills as well as the recruitment and matching process.

Results: Previous resident training was predominantly in pediatrics (49%).

Epigenetics and primary care.

Epigenetics, the study of functionally relevant chemical modifications to DNA that do not involve a change in the DNA nucleotide sequence, is at the interface between research and clinical medicine. Research on epigenetic marks, which regulate gene expression independently of the underlying genetic code, has dramatically changed our understanding of the interplay between genes and the environment. This interplay alters human biology and developmental trajectories, and can lead to programmed human disease years after the environmental exposure.

Genetic and genomic literacy in pediatric primary care.

A colloquium on genetic literacy in pediatric primary care sponsored by the Health Resources and Services Administration Maternal and Child Health Bureau was held at the American Academy of Pediatrics headquarters on October 2-3, 2012. The overarching goal of the colloquium was to provide context for delivery of genetics-related services in day-to-day pediatric primary care practice, encompassing 3 dimensions of medicine: prevention, diagnosis, and management. Participants considered the whole spectrum of disease, from rare disorders to common disorders, the genetics-related components of which are often overlooked.

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations.

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide.

Genetic services and attitudes in primary care pediatrics.

Given the integral role primary care pediatricians (PCPs) play in caring for children with genetic conditions, we aimed to identify current practices of PCPs regarding genetic patients, their attitudes toward genetic medical care and their choices regarding family history taking. We conducted an on-line survey of a national convenience sample of PCPs associated with the American Academy of Pediatrics' Quality Improvement Innovation Networks. Eighty-eight respondents (29% response rate) were included in the analysis.

Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder.

Purpose: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and café-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1.

Methods: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Campanacci syndrome or Jaffe-Campanacci syndrome-related features.

A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt & pepper syndrome, a neurocutaneous disorder with altered glycolipid and glycoprotein glycosylation.

'Salt & Pepper' syndrome is an autosomal recessive condition characterized by severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic facial features and altered dermal pigmentation. High-density SNP array analysis performed on siblings first described with this syndrome detected four shared regions of loss of heterozygosity (LOH). Whole-exome sequencing narrowed the candidate region to chromosome 2p11.

Clinical utility of the X-chromosome array.

Previous studies have limited the use of specific X-chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X-chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X-linked conditions.

Improving newborn screening follow-up in pediatric practices: quality improvement innovation network.

Objective: To implement a 6-month quality improvement project in 15 primary care pediatric practices to improve short-term newborn screening (NBS) follow-up.

Methods: At the start of the project, each practice completed a survey to evaluate office systems related to NBS and completed a chart audit. Practice teams were provided information about NBS and trained in quality-improvement methods, and then implemented changes to improve care.

Health supervision for children with fragile X syndrome.

Fragile X syndrome (an FMR1-related disorder) is the most commonly inherited form of mental retardation. Early physical recognition is difficult, so boys with developmental delay should be strongly considered for molecular testing. The characteristic adult phenotype usually does not develop until the second decade of life.

Neuro-ophthalmology and the Anti-GQ1b antibody syndromes.

The discovery of the association of the anti-GQ1b IgG antibody with the postinfectious clinical syndromes of ophthalmoplegia, ataxia, and areflexia helped house the phenotypes of the Miller Fisher syndrome (MFS), atypical MFS, Guillain-Barré syndrome with ophthalmoplegia, and Bickerstaff's brainstem encephalitis under one roof. The neuro-ophthalmologic signs classically predominate and may vary from case to case, but they maintain clinically recognizable patterns that assist with the diagnosis. The identification of a common lipopolysaccharide on the plasma membrane in human cranial and peripheral nerves at the GQ1b epitope and on infectious particles of bacteria and viruses (ie, Campylobacter jejuni) demonstrates molecular mimicry.

Fragile X syndrome detection in newborns-pilot study.

Purpose: Fragile X syndrome is the most common form of hereditary intellectual disability. Detection of the fragile X phenotype in the prepubertal period is very difficult, and early detection might assist in early developmental intervention and reproductive counseling. A pilot study was conducted to establish the feasibility of newborn screening for fragile X syndrome.

Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities.

We have identified disruptions in the dedicator of cytokinesis 8 gene, DOCK8, in two unrelated patients with mental retardation (MR). In one patient, a male with MR and no speech, we mapped a genomic deletion of approximately 230 kb in subtelomeric 9p. In the second patient, a female with mental retardation and ectodermal dysplasia and a balanced translocation, t(X;9) (q13.

Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia.

Pacman dysplasia has been previously reported to be a lethal skeletal dysplasia with epiphyseal stippling and osteoclastic overactivity. We report on a sibling of a fetus previously reported as Pacman dysplasia. This infant has a clinical course consistent with mucolipidosis type II (I-cell disease) along with confirmatory biochemical, cytologic, and radiographic evidence.