Brain Evaluation by Dual PET/CT with [18F] FDOPA and [18F] FDG in Differential Diagnosis of Parkinsonian Syndromes.

Parkinsonian syndromes are considered clinicopathological conditions that are challenging to diagnose. Molecular imaging with [18F]-FDOPA and [18F]-FDG contributes to a more accurate clinical diagnosis by evaluating presynaptic dopaminergic pathways and glucose metabolism, respectively. The aim of this study was to correlate diagnoses made from dual PET/CT with the initial clinical diagnoses, as well as during follow-ups in patients with Parkinsonian syndromes. A secondary objective was to describe the imaging findings. Methods: A total of 150 patients with a clinical diagnosis of neurodegenerative Parkinsonism were evaluated using dual PET/CT. Clinically, 82% were diagnosed with PD, while the remaining 18% had an atypical Parkinsonism. Results: Using dual PET/CT, the most frequent diagnosis was PD in 67% of the patients, with the rest being diagnosed with an atypical Parkinsonism. In an agreement analysis between the initial clinical diagnosis and the imaging diagnosis by dual PET/CT, a concordance of 94.1% (n = 95) was observed for PD. In the remaining patients, the clinical diagnosis differed from that suggested by dual PET/CT, with atypical Parkinsonian syndromes being diagnosed as DLB in 40% (n = 4), PSP in 46.7% (n = 7), MSA-C in 75% (n = 6), MSA-P in 70% (n = 7), and CBD in 66.7% (n = 4). A total of 38.66% (n = 58) of patients were followed up (median follow-up of 27 months), with a Kappa coefficient of 0.591 (p < 0.001), suggesting substantial agreement. Conclusions: Dual FDOPA-FDG PET/CT demonstrated moderate agreement with the initial clinical diagnosis of Parkinsonism and moderate to substantial agreement during follow-up. This dual technique, therefore, stands out in differentiating between types of Parkinsonisms.

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy

ABSTRACT Background: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limb-girdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. Objective: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. Methods: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. Results: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. Conclusions: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy.

BACKGROUND: Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limbgirdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness. OBJECTIVE: Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation. METHODS: Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing. RESULTS: NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected. CONCLUSIONS: This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.