Performance of Dysmorphology-Based Screening for Genetic Disorders in Pediatric Congenital Heart Disease Supports Wider Genetic Testing.

Background: Dysmorphology evaluation is important for congenital heart disease (CHD) assessment, but there are no prior investigations quantifying the screening performance compared to standardized genetics evaluations. We investigated this through systematic dysmorphology assessment in CHD patients with standardized genetic testing in primarily pediatric patients with CHD.

Methods: Dysmorphology evaluations preceding genetic testing results allowed us to test for associations between dysmorphic status and genetic diagnoses while adjusting for extracardiac anomalies (ECAs).

Outcomes in 14 live births resulting from Pegvaliase-treated pregnancies in PKU-affected females.

Background: Adults with PKU have difficulty maintaining plasma phenylalanine (Phe) in the range that is safe for neurologic function. Elevated plasma Phe is a risk factor for congenital anomalies and developmental delay in offspring resulting from pregnancies with poor Phe control in women with PKU. Enzyme supplementation with pegvaliase allows adults with PKU to eat an unrestricted diet and have plasma Phe levels in a safe range for pregnancy but pegvaliase has not been approved for use in pregnant females with PKU.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

Objective: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS).

Methods: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score.

Relationship satisfaction in adults with phenylketonuria is positively associated with following recommended treatment, having a partner involved in management, and maintaining good health.

Rationale: Phenylketonuria (PKU) is a metabolic condition that requires treatment for life. There is increasing evidence that chronic illnesses put strain on relationships and marriages. However, no studies have examined the unique factors that metabolic conditions have on affected individuals and their relationship satisfaction.

Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.

Context: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled.

Objective: The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.

Comparison of willingness and preference for genetic counseling via telemedicine: before vs. during the COVID-19 pandemic.

The COVID-19 pandemic required genetic counseling services, like most outpatient healthcare, to rapidly adopt a telemedicine model. Understanding the trends in patients' preferences for telemedicine relative to in-person service delivery both before and after the advent of the COVID-19 pandemic may aid in navigating how best to integrate telemedicine in a post-COVID-19 era. Our study explored how respondents' willingness to use, and preference for, telemedicine differed from before to after the onset of the COVID-19 pandemic.

Use of pegvaliase in the management of phenylketonuria: Case series of early experience in US clinics.

Objective: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers.

Methods: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings.

Palynziq clinic: One year and 43 patients later.

Pegvaliase-pqpz (Palynziq) is an enzyme substitution therapy FDA approved May 2018 to treat phenylketonuria in adults with blood phenylalanine levels greater than 600 μmol/L (10 mg/dL). Pegvaliase is administered via subcutaneous injection and carries a high risk of side effects including anaphylaxis. A consensus statement on its use recommends careful education and monitoring of patients.

The progression of Wiedemann-Steiner syndrome in adulthood and two novel variants in the KMT2A gene.

Wiedemann-Steiner syndrome is a genetic condition associated with dysmorphic facies, hypertrichosis, short stature, developmental delay, and intellectual disability. Congenital malformations of the cerebral, cardiac, renal, and optic structures have also been reported. Because the majority of reported individuals with this condition have been under age 20, the long-term prognosis is not well defined.

Survival of a Male Infant with a Familial Xp11.4 Deletion Causing Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase (OTC) deficiency is well known to cause severe neonatal hyperammonemia in males with absent enzyme activity. In families with large deletions of the X chromosome involving OTC and other contiguous genes, male infants appear to have an even more severe course. Notably, there are no published reports of these males surviving to liver transplant, even in cases where the diagnosis was known or suspected at birth.

Compound heterozygous mutations in desmoplakin associated with skin fragility, follicular hyperkeratosis, alopecia, and nail dystrophy.

Desmoplakin mutations are associated with a wide variety of phenotypes affecting the skin, nails, hair, and heart. A 21-month-old boy was born with multiple erosions resembling epidermolysis bullosa, complete alopecia, nail dystrophy, palmoplantar keratoderma, and areas of follicular hyperkeratosis. He was found to have two heterozygous mutations in the desmoplakin gene: c.

Novel phenotype of 5p13.3-q11.2 duplication resulting from supernumerary marker chromosome 5: implications for management and genetic counseling.

Background: Supernumerary marker chromosomes derived from chromosome 5 (SMC5) and 5p13 duplication syndrome are rare disorders, and phenotypic descriptions of patients are necessary to better define genotype-phenotype correlations for accurate, comprehensive genetic counseling. The purpose of this study is to highlight the unique findings of a patient with a 5p13.3-q11.

Cancer Genetic Counselors' Current Practices and Attitudes Related to the Use of Tumor Profiling.

Tumor profiling (TP) is primarily used to identify driver mutations within a tumor for treatment purposes, but it may also identify germline mutations. Current involvement of cancer genetic counselors (GCs) in the TP process is not clear. Members of the National Society of Genetic Counselors Cancer Special Interest Group were invited to participate in a confidential, web-based survey to characterize current practices and attitudes related to the use of TP.

A distinct X-linked syndrome involving joint contractures, keloids, large optic cup-to-disc ratio, and renal stones results from a filamin A (FLNA) mutation.

We further evaluated a previously reported family with an apparently undescribed X-linked syndrome involving joint contractures, keloids, an increased optic cup-to-disc ratio, and renal stones to elucidate the genetic cause. To do this, we obtained medical histories and performed physical examination on 14 individuals in the family, five of whom are affected males and three are obligate carrier females. Linkage analysis was performed on all but one individual and chromosome X-exome sequencing was done on two affected males.

An infant with large fontanelles, aplasia cutis congenita, tessier facial cleft, polydactyly inversus, and toe syndactyly: a previously undescribed syndrome?

We report on a 5-month-old female with large and widely spaced anterior and posterior fontanelles, aplasia cutis congenita, Tessier 3 oblique facial cleft, polydactyly, and syndactyly of toes. The polydactyly is unusual as an accessory finger is attached to the left fifth finger with mirrored, end-to-end fusion. We are naming this anomaly "polydactyly inversus.