Exploring genetic counselors' practice of discussing clinical trials with patients.

Despite concerted and accelerated efforts to increase the knowledge of medicine and disease via clinical studies, clinical trials continue to face low enrollment for all patient groups. The dissemination of the availability of clinical trials to individuals with or at risk for hereditary disorders is critical. This study acts as a foundation in determining an unexplored role of clinical trial discussion in genetic counseling practice.

De novo FRMD5 Missense Variants in Patients with Childhood-Onset Ataxia, Prominent Nystagmus, and Seizures.

Background: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities.

Objectives: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.

Novel THAP1 missense variant with incomplete penetrance in a case of generalized young onset dystonia showing good response to deep brain stimulation.

We describe a case of young onset generalized dystonia, harboring a previously unreported likely pathogenic THAP1 missense variant (c.109 G > A; p.Glu37Lys) that was inherited from her unaffected father.

Novel bi-allelic FBXO7 variants in a family with early-onset typical Parkinson's disease.

Bi-allelic mutations in FBXO7 are classically associated with a complex phenotype, known as parkinsonian-pyramidal syndrome. We describe two brothers affected by typical early onset Parkinson's disease (EOPD), who carry novel compound heterozygous variants in FBXO7. Our report highlights that typical EOPD can be part of an expanding FBXO7-related phenotype.

Expanding the spectrum of KCNJ6-related disorders: Milder phenotype with pathological startle responses.

Keppen-Lubinsky syndrome is caused by pathogenic variants in KCNJ6, which encodes the inwardly rectifying channel subfamily J6. The four confirmed cases reported to date were characterized by severe intellectual disability, global developmental delay, feeding difficulties, and dysmorphic features. All but one of the cases also had a severe form of lipodystrophy, resulting in tightly adherent facial skin and appearance of premature aging.

mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion.

Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTORC1 signalling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions, but these variants are increasingly detected and reported by clinical genetic testing in individuals with epilepsy.

CACNA1H variants are not a cause of monogenic epilepsy.

CACNA1H genetic variants were originally reported in a childhood absence epilepsy cohort. Subsequently, genetic testing for CACNA1H became available and is currently offered by commercial laboratories. However, the current status of CACNA1H as a monogenic cause of epilepsy is controversial, highlighted by ClinGen's recent reclassification of CACNA1H as disputed.

The Impact of Family History on the Clinical Features of Huntington's Disease.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset.

Reproductive decision-making among individuals at risk for familial amyotrophic lateral sclerosis.

This qualitative study explored the reproductive decision-making process in individuals at 50% risk for familial amyotrophic lateral sclerosis (FALS) from families with a known genetic mutation. We spoke with 10 individuals utilizing a semi-structured interview. Participants had a first-degree relative with FALS, made reproductive decisions in the past 30 years and did not know their genetic status during decision-making.