Dataset Information

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

ABSTRACT:

Background

A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient.

Methods

We performed genetic analysis of the NKX2.1 gene in an infant with no neonatal respiratory distress and near-normal results at neonatal screening test for congenital hypothyroidism, choreoathetosis, ataxia and delayed independent walking.

Results

A novel mutation of the NKX2.1 gene has been identified, that is responsible for a mild framework of congenital hypothyroidism and neurological symptoms.

Conclusions

The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended.

SUBMITTER: Monti S

PROVIDER: S-EPMC4477322 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

Monti Sara S Nicoletti Annalisa A Cantasano Antonella A Krude Heiko H Cassio Alessandra A

Italian journal of pediatrics 20150624

<h4>Background</h4>A highly variable phenotype characterized by thyroid, respiratory and neurological defects has been reported in an already established group of disorders namely NKX2.1-related disorders. We describe here the case of an infant with a novel mutation of the NKX2.1 gene characterized by mild clinical presentation. Aim of the study was to elucidate the genotype-phenotype correlation in our patient.<h4>Methods</h4>We performed genetic analysis of the NKX2.1 gene in an infant with no ...[more]

PMID: 26103969

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Project description:BackgroundPKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort.Study designCase series, January 2010 to March 2016.Settings & participantsGenkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease.OutcomesMolecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate.ResultsThe Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD.LimitationsYounger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers.ConclusionsPatients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.

Project description:ObjectiveThunderclap-like severe headache or consciousness disturbance is the common "typical" clinical presentation after aneurysmal subarachnoid hemorrhage (aSAH); however, a slowly developing "atypical" clinical pattern, with mild headache, vomiting, or dizziness, is frequently noted in elderly patients. The aim of this study was to evaluate the clinical characteristics of this "atypical" subgroup, as well as related factors associated with the presence of these mild symptoms.MethodsThe data of 176 elderly patients (≥70 years old) with ruptured intracranial aneurysms (IAs) treated at our center from January 2016 to January 2020 were retrospectively collected and analyzed. The patients were divided into "typical" and "atypical" groups based on their initial and development of clinical symptoms after the diagnosis of aSAH. Intergroup differences were analyzed, and factors related to the presence of these two clinical patterns were explored through multiple logistic regression analyses.ResultsDespite significant admission delay (P < 0.001) caused by mild initial symptoms with slow development, patients in the "atypical" group achieved better clinical prognosis, as indicated by a significantly higher favourable outcome ratio and lower death rate upon discharge and at different time points during the 1-year follow-up, than the "typical" group (P < 0.05). Multiple logistic regression analysis revealed that modified Fisher grade III-IV (OR = 11.182, P = 0.003), brain atrophy (OR = 10.010, P = 0.001), a larger lesion diameter (OR = 1.287, P < 0.001) and current smoking (OR = 5.728, P < 0.001) were independently associated with the presence of "typical" symptoms. Aneurysms with wide necks (OR = 0.013, P < 0.001) were independently associated with the presence of "atypical" symptoms.Conclusions"Atypical" presentations, with mild clinical symptoms and slow development, were commonly recorded in elderly patients after the onset of aSAH. Despite the prolonged admission delay, these "atypical" patients achieved better clinical outcomes than those with "typical" symptoms. Modified Fisher grade (III-IV), current smoking, brain atrophy and larger lesion diameter were factors predictive of "typical" symptoms, while aneurysms with wide necks were independently associated with "atypical" symptoms.

Dataset Information

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

Background

Methods

Results

Conclusions

Publications

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation.

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