Incidental Findings Identified by Prenatal Microarray Analysis and Consensus Reporting Criteria of the Catalan Public Health Network XIGENICS.

Objective: The study aimed to evaluate the frequency of pathogenic copy number variants (CNVs) classified as incidental findings (IFs) in prenatal diagnosis and to develop consensus recommendations for standardizing their reporting across six centers within the Catalan public health system (XIGENICS network).

Method: A retrospective review of 4219 consecutive prenatal microarrays performed within the network from 2018 to 2023 was conducted, including all referral reasons. To develop consensus recommendations, several discussion meetings were held along with an extensive review of the existing literature.

Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.

Background: Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844).

Methods: The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing.

Novel variant in ACTA1 identified in a fetus with akinesia deformation sequence and cortical development delay.

We present a case of fetal akinesia deformation sequence due to nemaline myopathy (NM). In addition to the muscle manifestations, prenatal observations included an enlarged subarachnoid space and delayed cortical development. Trio whole-exome sequencing revealed a de novo novel pathogenic variant in the ACTA1 gene, which encodes skeletal muscle alpha-actin.

GLYT1 encephalopathy: Further delineation of disease phenotype and discussion of pathophysiological mechanisms.

GLYT1 encephalopathy is a form of glycine encephalopathy caused by disturbance of glycine transport. The phenotypic spectrum of the disease has not yet been completely described, as only four unrelated families with the disorder have been reported to date. Common features of affected patients include neonatal hypotonia, respiratory failure, encephalopathy, myoclonic jerks, dysmorphic features, and musculoeskeletal anomalies.