Undifferentiated psychosis or schizophrenia associated with vermis-predominant cerebellar hypoplasia.

Am J Med Genet A

Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.

Published: March 2024

AI Article Synopsis

  • Schizophrenia (SCZ) shows significant genetic heritability, but specific genetic risk variants are not well understood; classifying SCZ into distinct endophenotypes may help identify these variants.
  • The study presents 17 individuals with SCZ-related characteristics and shared brain imaging findings, revealing classic psychiatric features alongside new neuropsychiatric traits like decreased IQ, memory issues, and attention deficits.
  • Imaging results showed a consistent pattern of posterior vermis predominant cerebellar hypoplasia, suggesting a potential endophenotype of SCZ rather than Dandy-Walker malformation, although specific genetic variants remain to be identified.

Article Abstract

Schizophrenia (SCZ) is a well-studied neuropsychiatric condition that has been shown to have a high degree of genetic heritability. Still, little data on the specific genetic risk variants associated with the disease exists. Classification of the SCZ phenotype into SCZ-related endophenotypes is a promising methodology to parse out and elucidate the specific genetic risk variants for each. Here, we present a series of 17 previously reported individuals and a new proband with similar SCZ-related neuropsychiatric characteristics and shared brain imaging findings. Unsurprisingly, these individuals shared classic psychiatric features of SCZ. Interestingly, we also identified shared neuropsychiatric features in this series of individuals that had not been highlighted previously. A consistently decreased IQ, memory impairment, sleep and speech disturbances, and attention deficits were commonly reported findings. The brain imaging findings among these individuals also consistently showed posterior vermis predominant cerebellar hypoplasia (CBLH-V). Most individuals' diagnoses were initially described as Dandy-Walker malformation; however, our independent review of imaging suggests a more consistent pattern of posterior vermis predominant cerebellar hypoplasia rather than true Dandy-Walker malformation. While the specific genetic risk variants for this endophenotype are yet to be described, the aim of this paper is to present the shared neuropsychiatric features and consistent, symmetrical brain image findings which suggest that this subset of individuals comprises an endophenotype of SCZ with a high genetic solve rate.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.63416DOI Listing

Publication Analysis

Top Keywords

cerebellar hypoplasia
12
specific genetic
12
genetic risk
12
risk variants
12
brain imaging
8
imaging findings
8
shared neuropsychiatric
8
neuropsychiatric features
8
posterior vermis
8
vermis predominant
8

Similar Publications

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Am J Hum Genet

January 2025

Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; Center for Rare Disease, University of Tübingen, 72076 Tübingen, Germany; Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE).

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

View Article and Find Full Text PDF

A 13-month-old boy presented to the pediatric ophthalmology clinic at BC Children's Hospital for strabismus assessment. On examination he had a right facial hemangioma, left ptosis, and left exotropia and hypotropia. Magnetic resonance imaging and magnetic resonance angiography of his head demonstrated posterior cerebral artery tortuosity producing mild mass effect on the left oculomotor nerve.

View Article and Find Full Text PDF

Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.

View Article and Find Full Text PDF

Loss-of-function of DDR1 is responsible for a chondrodysplasia with multiple dislocations.

J Bone Miner Res

December 2024

Paris Cité University, Reference center for skeletal dysplasia, INSERM UMR 1163, Imagine Institute, Necker Enfants Malades Hospital (AP-HP), Paris, France.

Chondrodysplasias with multiple dislocations are rare skeletal disorders characterized by hyperlaxity, joint dislocations, and growth retardation. Chondrodysplasias with multiple dislocations have been linked to pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis. In this study, by exome sequencing analysis, we identified a homozygous nonsense variant (NM_001297654.

View Article and Find Full Text PDF

RORA-neurodevelopmental disorder: a unique triad of developmental disability, cerebellar anomalies, and myoclonic seizures.

Genet Med

December 2024

Genetics Department, Hospices Civils de Lyon, Lyon, France; Neuromyogene Institute, Pathology and Genetics of neuron and muscle, CNRS UMR 5261 INSERM U1315, University of Lyon - Université Claude Bernard Lyon 1, Lyon, France. Electronic address:

Article Synopsis
  • RORA is a gene linked to the development and function of the cerebellum, and this study explores the largest group of individuals with RORA-related neurodevelopmental disorders (RORA-NDD).
  • The study involved 40 participants with various pathogenic variants of RORA, revealing a range of clinical features including developmental and intellectual disabilities, as well as cerebellar symptoms that can vary in onset and severity.
  • Findings indicate that certain missense variants are associated with more severe cerebellar issues, and common elements of RORA-NDD include developmental disabilities, cerebellar symptoms, and different types of myoclonic epilepsy.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!