DPAGT1 Deficiency with Encephalopathy (DPAGT1-CDG): Clinical and Genetic Description of 11 New Patients.

Pathogenic mutations in DPAGT1 cause a rare type of a congenital disorder of glycosylation termed DPAGT1-CDG or, alternatively, a milder version with only myasthenia known as DPAGT1-CMS. Fourteen disease-causing mutations in 28 patients from 10 families have previously been reported to cause the systemic form, DPAGT1-CDG. We here report on another 11 patients from 8 families and add 10 new mutations. Most patients have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. We also present data on three affected females that are young adults and have a somewhat milder, stable disease. Our findings expand both the molecular and clinical knowledge of previously published data but also widen the phenotypic spectrum of DPAGT1-CDG.

A tailored approach to family-centered genetic counseling for cystic fibrosis newborn screening: the Wisconsin model.

This article describes the development of a tailored family-centered approach to genetic counseling following abnormal newborn screening (NBS) for cystic fibrosis (CF). A genetic counseling consortium reviewed research literature, selected theoretical frameworks, and incorporated counseling psychology micro skills. This innovative intervention integrated theories and empirically validated techniques. Pilot testing and parent feedback confirmed satisfaction with and feasibility of the approach designed to (a) minimize parents' distress, (b) facilitate parents' understanding, (c) increase parents' capacities to use genetic information, and (d) enhance parents' experiences with genetic counseling. Counselors engage in a highly interactive process of evaluating parents' needs and tailoring assessments and interventions that include a therapeutic environment, the family's emotional needs, parents' informational needs, and a follow-up plan. This promising new model is the first to establish a theory-driven, evidence-based standard for genetic counseling in the context of NBS for CF. Additional research will evaluate the model's efficacy in clinical practice.

Analysis of 88 adult patients referred for genetics evaluation.

We present a series of 88 adult patients referred for diagnostic genetic services in two settings. Patients referred for prenatal diagnosis, adult-onset neurodegenerative disease or cancer susceptibility counseling were specifically excluded from analysis. Information was obtained regarding age, gender, referral sources, previous genetics evaluation, referring diagnosis, final diagnosis, diagnostic test, and recommendations. The patients were able to be grouped into seven general categories: multiple congenital anomalies with or without mental retardation (26 patients), collagen-connective tissue disorders (18 patients), mental retardation (12 patients), chromosomal abnormalities (12 patients), bone growth disorders (6 patients), endocrine/metabolic (8 patients), and miscellaneous (6 patients). Patients and referring providers were not surveyed regarding utility of the evaluation. However, genetics notes were reviewed on all patients and potential benefits of the evaluation were identified. All patients had at least one potential benefit, with the majority having several. This study represents one of the largest published groups of non-institutionalized adult patients that have undergone comprehensive genetic evaluation. The role of the clinical geneticist as a member of the health care team in this population will be discussed.

Macrocephaly, distinct craniofacial appearance, and spastic paraplegia: a new case and expansion of the phenotype.

An adult female patient is presented with macrocephaly, mental retardation, seizures, spastic paraplegia and distinctive craniofacial appearance. We believe she represents the fourth case of the Fryns macrocephaly, distinct craniofacial appearance and spastic paraplegia syndrome. Cardinal features are discussed and additional phenotypic manifestations are discussed.