Musculoskeletal and neurological manifestations in a cohort of Egyptian Familial Mediterranean fever patients: genotype-phenotype correlation

Ahmed, Mohamed H.; Ibrahim, Amira; Ragab, Salma M.; Mahros, Ayah M.

doi:10.1186/s43166-021-00106-w

Cited by 4 publications

(1 citation statement)

References 43 publications

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“…Familial Mediterranean fever (FMF) is the most common inherited periodic auto‐inflammatory disease with multiple systemic manifestations. 3 …”

Section: Introductionmentioning

confidence: 99%

Solving a diagnostic dilemma in a patient with periodic fever—When the pieces of the puzzle finally fit

Shukla,

Sarabjit Singh,

Ranghell

et al. 2024

Clinical Case Reports

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Key Clinical MessageThe lack of pediatric subspecialists locally prior to 5 years ago, meant that some of our patients with rare, relapsing conditions were left behind. Familial Mediterranean fever can be diagnosed clinically and supported via genetic panel studies. Although neurological symptoms can be non‐specific, this system symptomatology may lead patients and carers to seek medical attention. When neurological symptoms progress, seemingly refractory to first‐line treatment, or suggestive of colchicine resistance, CNS demyelination should be considered by the neurologist.AbstractFamilial Mediterranean fever (FMF) is an inherited disorder with episodic fevers accompanied by pain in the abdomen, joints, or chest. It is a clinical entity that can be confirmed with a specific genetic mutation. Neurological symptoms have not been a focal point in clinical case descriptions. We aim to present the long road to diagnosing our patient, where the diagnostic clues centered around her neurological symptoms.

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“…Familial Mediterranean fever (FMF) is the most common inherited periodic auto‐inflammatory disease with multiple systemic manifestations. 3 …”

Section: Introductionmentioning

confidence: 99%

Solving a diagnostic dilemma in a patient with periodic fever—When the pieces of the puzzle finally fit

Shukla,

Sarabjit Singh,

Ranghell

et al. 2024

Clinical Case Reports

View full text Add to dashboard Cite

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Association of rare variants in genes of immune regulation with pediatric autoimmune CNS diseases

et al. 2022

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Background There is a gap in the literature regarding genetic underpinnings of pediatric autoimmune CNS diseases. This study explored rare gene variants implicated in immune dysregulation within these disorders. Methods This was a single-center observational study of children with inflammatory CNS disorder who had genetic testing through next generation focused exome sequencing targeting 155 genes associated with innate or adaptive immunity. For in silico prediction of functional effects of single-nucleotide variants, Polymorphism Phenotyping v2, and Sorting Intolerant from Tolerant were used, and Combined Annotation Dependent Depletion (CADD) scores were calculated. Identified genes were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results Of 54 patients, 42 (77.8%) carried variant(s), among which 12 (22.2%) had 3-8 variants. Eighty-eight unique singlenucleotide variants of 55 genes were identified. The most variants were detected in UNC13D, LRBA, LYST, NOD2, DOCK8, RNASEH2A, STAT5B, and AIRE. The majority of variants (62, 70.4%) had CADD > 10. KEGG pathway analysis revealed seven genes associated with primary immunodeficiency (Benjamini 1.40E − 06), six genes with NOD-like receptor signaling (Benjamini 4.10E − 04), five genes with Inflammatory Bowel Disease (Benjamini 9.80E − 03), and five genes with NF-kappa B signaling pathway (Benjamini 1.90E − 02). Discussion We observed a high rate of identification of rare and low-frequency variants in immune regulatory genes in pediatric neuroinflammatory CNS disorders. We identified 88 unique single-nucleotide variants of 55 genes with pathway analysis revealing an enrichment of NOD2-receptor signaling, consistent with involvement of the pathway within other autoinflammatory conditions and warranting further investigation.

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Neurological manifestations among Egyptian children with familial Mediterranean fever

Abu Shady,

Osman,

Elshennawy

et al. 2024

Egypt Rheumatol Rehabil

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Background Familial Mediterranean fever (FMF) is an auto-inflammatory periodic disorder resulting from mutations in the Mediterranean fever gene. Although it is considered a polyserositis disease, neurological-associated symptoms were also reported among different populations. Aim of the work To detect the frequency of neurological manifestations among Egyptian children with FMF and to investigate its association with various disease characteristics and various FMF gene mutations. Patients and methods This is an analytical cross-sectional study that enrolled 300 FMF children. Neurological manifestations such as headache, paresthesia, convulsions, tremors, breath-holding attacks, and syncope were reported. The dose, duration, and compliance with colchicine and the international severity scoring system for FMF (ISSF) were recorded. Serum amyloid A and gene mutations were recorded from patients’ files. Results The mean age of the patients was 10.35 ± 2.89 years; 158 (52.7%) were females, and 142 (47.3%) were males (F:M, 1.1:1), age at onset 4.67 ± 2.35 years and disease duration 3.28 ± 1.31 years. Genetic testing revealed positive MEFV gene mutation in 89.3%. Serum amyloid A was elevated in 33.7%. All patients were treated with colchicine, and 81.3% were compliant. Neurological manifestations were detected in 160 (53.3%) patients. Headache was the most common symptom in 136 (45.3%), followed by paraesthesia in 76 (25.3%). Epilepsy was present in 7 (2.3%) cases. Headaches were most frequent among patients with compound heterozygous mutation, severe ISSF scores, and poor compliance with colchicine. Conclusion Egyptian children with FMF present with various neurological manifestations. Headache and paresthesia were the most frequent, especially with the compound heterozygous mutations, severe ISSF score, and among colchicine non-compliant patients. Rheumatologists and neurologists should be aware of these manifestations and address the importance of disease control and adherence to colchicine to avoid or decrease these manifestations. Persistent unexplained headache or other neurological manifestations, in the presence of other symptoms suggestive of FMF or high serum amyloid A, should raise suspicion of FMF, and genetic testing should be requested. A multidisciplinary approach must be considered when managing these children.

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Musculoskeletal and neurological manifestations in a cohort of Egyptian Familial Mediterranean fever patients: genotype-phenotype correlation

Cited by 4 publications

References 43 publications

Solving a diagnostic dilemma in a patient with periodic fever—When the pieces of the puzzle finally fit

Solving a diagnostic dilemma in a patient with periodic fever—When the pieces of the puzzle finally fit

Association of rare variants in genes of immune regulation with pediatric autoimmune CNS diseases

Neurological manifestations among Egyptian children with familial Mediterranean fever

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