Evidence map›Paper›PMID 41423511›Full record

ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2025

A novel NKX2-1 frameshift variant expanding the genetic landscape of benign hereditary chorea.

Simone Aloisio, Martina De Riggi, Adriana Martini, Sofia Grandolfo, Daniele Birreci, Luca Angelini, Bianca Laura Cinicola, Alberto Spalice, Matteo Bologna

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Simone AloisioDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy.
Martina De RiggiDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy.
Adriana MartiniDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy.
Sofia GrandolfoDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy.
Daniele BirreciDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy.
Luca AngeliniIRCCS Neuromed, Pozzilli, Italy.
Bianca Laura CinicolaDepartment of Maternal and Child Health and Urogynecological Sciences, Sapienza University of Rome, Rome, Italy.
Alberto SpaliceDepartment of Maternal and Child Health and Urogynecological Sciences, Sapienza University of Rome, Rome, Italy.
Matteo BolognaDepartment of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, Rome, 00185, Italy. matteo.bologna@uniroma1.it.ORCID http://orcid.org/0000-0003-0165-0833

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionBenign hereditary chorea (BHC) is a rare childhood-onset hyperkinetic disorder caused by pathogenic variants in NKX2-1. It typically follows a stationary or only mildly progressive course and may be associated with thyroid and respiratory involvement, constituting the "brain-lung-thyroid" syndrome.

methodsWe report the case of a girl carrying a novel heterozygous NKX2-1 frameshift variant. Clinical assessment included longitudinal neurological examinations, neuroimaging, laboratory testing, cardiological evaluation, and genetic analysis.

resultsA 6-year-old girl, first evaluated at age 3 for delayed psychomotor milestones, showed choreiform movements with motor impersistence, milkmaid's grip, and imbalance, sparing the forehead. Brain MRI was normal. Thyroid dysfunction was documented since foster care, while no respiratory involvement was reported. Genetic testing in August 2024 identified a novel heterozygous NKX2-1 frameshift variant (c.246_250del p.Met83AlafsTer354), classified as likely pathogenic. At last follow-up, movements persisted but remained non-progressive. DISCUSSION: This case expands the mutational spectrum of NKX2-1-related disorders. The stationary course of chorea, together with thyroid involvement and absence of pulmonary disease, aligns with previous literature. Recognition of novel NKX2-1 variants is essential to improve genotype-phenotype correlations, avoid misdiagnosis with progressive pediatric choreic or ataxic syndromes, and provide accurate prognostic counselling, as most affected individuals achieve a favorable long-term functional outcome.

Indexed as

ChoreaFrameshift MutationThyroid Nuclear Factor 1ChildFemaleHumansNKX2-1 protein, humanThyroid Nuclear Factor 1Benign hereditary choreaFrameshift variantNKX2-1Pediatric movement disordersTTF-1

Identifiers

PMID41423511
PMCPMC12719338

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.