<scp>FINCA syndrome—Defining neurobehavioral phenotype in survivors into late childhood</scp>

Badura‐Stronka, Magdalena; Robert, Śmigiel; Rutkowska, Karolina; Sztefko, Krystyna; Hirschfeld, Adam Sebastian; Monkiewicz, Michał; Kosińska, Joanna; Wolańska, Ewelina; Rydzanicz, Małgorzata; Latos‐Bieleńska, Anna; Płoski, Rafał

doi:10.1002/mgg3.1899

Cited by 8 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combining the clinical features of our five novel patients with the previously described 13 patients ( Uusimaa et al, 2018 ; Brodsky et al, 2020 ; Rapp et al, 2021 ; Badura-Stronka et al, 2022 ) reveals the following: 10 patients have been reported as being alive (age between 4 and 61 years at the time of the publication), while eight were deceased (age at death between 10 months and 2 years, 5 months). Eight of the 18 patients were male.…”

Section: Discussionmentioning

confidence: 67%

“… Schematic representation of the NHLRC2 domain composition and amino acid substitutions identified from the FINCA patients. The patients reported here harbored variants presented above the corresponding domain; the variants presented in gray boxes have been described previously ( Uusimaa et al, 2018 ; Brodsky et al, 2020 ; Rapp et al, 2021 ; Badura-Stronka et al, 2022 ). …”

Section: Resultsmentioning

confidence: 99%

“…Since our initial report, more FINCA patients have been diagnosed worldwide ( Brodsky et al, 2020 ; Rapp et al, 2021 ; Badura-Stronka et al, 2022 ). Interstitial lung disease and recurrent infections are pronounced in almost all patients during infancy and can lead to death before the age of 2–3 years.…”

Section: Introductionmentioning

confidence: 99%

“…Interstitial lung disease and recurrent infections are pronounced in almost all patients during infancy and can lead to death before the age of 2–3 years. Alternatively, in some cases, the progressive disease stabilizes and the neurodevelopmental disorder (NDD) evolves as the key clinical finding ( Rapp et al, 2021 ; Badura-Stronka et al, 2022 ). FINCA is the first human disease known to be caused by recessive variants in the highly conserved NHLRC2.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease

Tallgren¹,

Kager²,

O’Grady³

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

PurposeFINCA disease (Fibrosis, Neurodegeneration and Cerebral Angiomatosis, OMIM 618278) is an infantile-onset neurodevelopmental and multiorgan disease. Since our initial report in 2018, additional patients have been described. FINCA is the first human disease caused by recessive variants in the highly conserved NHLRC2 gene. Our previous studies have shown that Nhlrc2-null mouse embryos die during gastrulation, indicating the essential role of the protein in embryonic development. Defect in NHLRC2 leads to cerebral neurodegeneration and severe pulmonary, hepatic and cardiac fibrosis. Despite having a structure suggestive of an enzymatic role and the clinical importance of NHLRC2 in multiple organs, the specific physiological role of the protein is unknown.MethodsThe clinical histories of five novel FINCA patients diagnosed with whole exome sequencing were reviewed. Segregation analysis of the biallelic, potentially pathogenic NHLRC2 variants was performed using Sanger sequencing. Studies on neuropathology and NHLRC2 expression in different brain regions were performed on autopsy samples of three previously described deceased FINCA patients.ResultsOne patient was homozygous for the pathogenic variant c.442G > T, while the other four were compound heterozygous for this variant and two other pathogenic NHLRC2 gene variants. All five patients presented with multiorgan dysfunction with neurodevelopmental delay, recurrent infections and macrocytic anemia as key features. Interstitial lung disease was pronounced in infancy but often stabilized. Autopsy samples revealed widespread, albeit at a lower intensity than the control, NHLRC2 expression in the brain.ConclusionThis report expands on the characteristic clinical features of FINCA disease. Presentation is typically in infancy, and although patients can live to late adulthood, the key clinical and histopathological features are fibrosis, infection susceptibility/immunodeficiency/intellectual disability, neurodevelopmental disorder/neurodegeneration and chronic anemia/cerebral angiomatosis (hence the acronym FINCA) that enable an early diagnosis confirmed by genetic investigations.

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease

Tallgren¹,

Kager²,

O’Grady³

et al. 2023

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…WES variants prioritization was performed as previously described. 7 In results, WES study in proband compound heterozygous variants in the SLC39A4 were identi ed (hg38 8:144414042-C > T, c.1203G > A NM_130849.4, p.(Trp401Ter) and hg38 8:144415989-C > T, c.295G > A, NM_130849.4, p.(Ala99Thr)) (Fig. 4).…”

Section: Case Report Methods and Resultsmentioning

confidence: 88%

Acrodermatitis enteropathica – diagnostic challenges

Sztupecka-Rutkowska

Wojciechowska

Heropolitańska-Pliszka

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Acrodermatitis enteropathica is a rare genetic metabolic disorder which results in poor absorption of zinc ions in digestive tract. Zinc is an important microelement in human body, that plays a crucial role in many metabolic and biochemical pathways in organism. Classic clinical manifestation of zinc deficiency, seen in about 20% of cases, is the triad of symptoms – acral and periorificial dermatitis, diarrhea and alopecia. Results: Here, we report a case of 16 months-old girl with atypical course of acrodermatitis enteropathica. First skin lesions appeared after infancy and initially presented as blisters treated as erythema multiforme without success. In that time epidermolysis bullosa was also considered by doctors. One month later the patient developed more severe clinical picture containing erythematous plaques, paronychia, alopecia suggesting acrodermatitis enteropathica, however laboratory test showed zinc serum level within reference ranges. Since anti-inflammatory topical corticosteroids and antibiotics used for a few weeks were not effective, further diagnostic procedures were introduced. Direct immunofluorescence excluded autoimmune skin disorders, whereas genetic study showed pathogenic mutation characteristic of acrodermatitis enteropathica in SCL39A4 gene. Although serum zinc level was normal, we observed theatrical improvement of healing skin lesions only after initiation of oral supplementation of zinc. Conclusions: Blisters and erythematous plaques especially located in traumatized areas developing in children may suggest several severe disorders like epidermolysis bullosa, linear IgA bullous dermatosis, epidermolytic ichthyosis, erythema multiforme, therefore we recommend rapid diagnostics containing immunological, genetic and biochemical tests in such cases, because making a proper diagnosis allows rapid initiation of a proper treatment and can improve life quality of patients and prevent distant consequences like mental and physical retardation in cases of metabolic disorders.

show abstract

FINCA syndrome—Defining neurobehavioral phenotype in survivors into late childhood

Badura‐Stronka

Robert

Rutkowska

et al. 2022

Molec Gen & Gen Med

Self Cite

View full text Add to dashboard Cite

Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome is a rare disease (OMIM #618278) with only 10 cases described until now from six families (Uusimaa et al. 2018;Brodsky et al., 2020, Rapp et al., 2021. The reported cases carry variants in NHL repeat containing two gene (NHLRC2) (Biterova et al., 2018).In the first report, released in 2018, three Finnish patients were described (Uusimaa et al., 2018). In the second one, published in 2020, one Ukrainian patient was reported (Brodsky et al., 2020). These reports were followed by a recent publication of Rapp et al. (2021), reporting on six additional patients from three families. Patients with FINCA have multi-organ symptoms, which can be manifested along with feeding problems, growth failure, chronic

show abstract

FINCA syndrome—Defining neurobehavioral phenotype in survivors into late childhood

Cited by 8 publications

References 18 publications

Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease

Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease

Acrodermatitis enteropathica – diagnostic challenges

FINCA syndrome—Defining neurobehavioral phenotype in survivors into late childhood

Contact Info

Product

Resources

About