NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement

Balicza, Péter; Grosz, Zoltán; Molnár, Viktor; Illés, Anett; Csabán, Dóra; Gézsi, András; Dézsi, Lívia; Zádori, Dénes; Vécsei, László; Molnár, Mária Judit

doi:10.3389/fgene.2018.00335

Cited by 14 publications

(14 citation statements)

References 15 publications

(13 reference statements)

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“…[ 35 ] Salvatore et al identified features of “empty sella” in two adult patients, whereby the abnormality was more marked in the parent who had longer disease duration [ 5 ]. Balicza et al reported a family where two patients with stop mutation of NKX2-1 gene had “empty sella” on MRI and pituitary hormone deficiencies [ 10 ]. The imaging features in the latter publication are strikingly similar to the patients in our series, supporting the hypothesis of progression over time.…”

Section: Resultsmentioning

confidence: 99%

“…Several TITF1/ NKX2-1 mutations have been identified, in which brain MR imaging was unremarkable. However, the presence of pituitary abnormalities has been described in a small proportion of BHC patients, 7 to date [7][8][9][10] This subset of patients raised the question of whether these findings were incidental or represented part of the variable BHC phenotype.…”

Section: Introductionmentioning

confidence: 99%

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Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

et al. 2022

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Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing. All four patients in the two families displayed a classic BHC phenotype. The targeted pituitary MR imaging demonstrated abnormal pituitary sella morphology. Genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients. The presence of the abnormal pituitary sella in two affected members of the same family supports the hypothesis that this sign is a distinct feature of the BHC phenotype spectrum due to mutations in the TITF1 gene. Interestingly, these abnormalities seem to develop in adult life and are progressive. They occur in at least 26% of patients affected with Brain-lung-thyroid syndrome. As a part of the management of these patients we recommend to perform follow-up MRI brain with dedicated pituitary imaging also in adult life as the abnormality can occur years after the onset of chorea.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

et al. 2022

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“…The association of ppituitary anomalies with NKX2-1 variants has been reported rarely in the literature. However, both point mutations involving NKX2-1 as well as a deletion of the entire gene [ 41 , 42 ] have been reported with pituitary and/or pituitary stalk anomalies. An affected father and his daughter were reported with respectively low LH levels, leading to hypogonadism, or low GH levels, causing short stature.…”

Section: Resultsmentioning

confidence: 99%

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

2020

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Pituitary stalk interruption syndrome is a rare disorder characterized by an absent or ectopic posterior pituitary, interrupted pituitary stalk and anterior pituitary hypoplasia, as well as in some cases, a range of heterogeneous somatic anomalies. A genetic cause is identified in only around 5% of all cases. Here, we define the genetic variants associated with PSIS followed by the same pediatric endocrinologist. Exome sequencing was performed in 52 (33 boys and 19 girls), including 2 familial cases single center pediatric cases, among them associated 36 (69.2%) had associated symptoms or syndromes. We identified rare and novel variants in genes (37 families with 39 individuals) known to be involved in one or more of the following—midline development and/or pituitary development or function (BMP4, CDON, GLI2, GLI3, HESX1, KIAA0556, LHX9, NKX2-1, PROP1, PTCH1, SHH, TBX19, TGIF1), syndromic and non-syndromic forms of hypogonadotropic hypogonadism (CCDC141, CHD7, FANCA, FANCC, FANCD2, FANCE, FANCG, IL17RD, KISS1R, NSMF, PMM2, SEMA3E, WDR11), syndromic forms of short stature (FGFR3, NBAS, PRMT7, RAF1, SLX4, SMARCA2, SOX11), cerebellum atrophy with optic anomalies (DNMT1, NBAS), axonal migration (ROBO1, SLIT2), and agenesis of the corpus callosum (ARID1B, CC2D2A, CEP120, CSPP1, DHCR7, INPP5E, VPS13B, ZNF423). Pituitary stalk interruption syndrome is characterized by a complex genetic heterogeneity, that reflects a complex phenotypic heterogeneity. Seizures, intellectual disability, micropenis or cryptorchidism, seen at presentation are usually considered as secondary to the pituitary deficiencies. However, this study shows that they are due to specific gene mutations. PSIS should therefore be considered as part of the phenotypic spectrum of other known genetic syndromes rather than as specific clinical entity.

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“…A szorongásos kórképek, valamint az obszesszívkompulzív zavarok előfordulása gyakoribb ebben a populációban [5]. A betegség hátterében a leggyakrabban a 7. kromoszóma hosszú karján lévő, 13 exonból álló ε-szarkoglikán-gén (SGCE) mutációi állnak, leírásra kerültek azonban már egyéb eltérések is [1,2,[6][7][8][9][10] (1. táblázat). A betegség patomechanizmusa részleteiben nem teljesen tisztázott.…”

Section: Táblázatunclassified

Zonisamidkezelés myoclonusdystoniában

et al. 2019

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Myoclonus-dystonia (DYT11) is a rare, autosomal dominant hereditary disorder clinically characterized by myoclonus and/or dystonia. The disease is most commonly caused by the mutations of the SGCE gene. Causative therapy is not available currently. Regarding symptomatic treatment, zonisamide, insulin therapy, carbamazepine and zolpidem may be utilized. If these drugs are not effective, bilateral globus pallidus internus deep brain stimulation may come into consideration. The aim of this study is to demonstrate the efficacy of zonisamide treatment in a Hungarian patient with genetically proven myoclonus-dystonia. Our 25-year-old female patient has had jerky, lightning-like movements since her childhood, mainly localized to her right upper limb. In addition, muscle cramps associated with writing and walking were also present. The symptoms were reduced by alcohol consumption. Brain MRI did not show any abnormality. Neurophysiological studies raised the possibility of subcortical myoclonus. After detailed phenotyping, genetic testing was performed, yielding the diagnosis of myoclonus-dystonia. A heterozygous mutation in the 6th exon of the SGCE gene at the position 709, resulting in an early stop codon (c.709C> T, p.Arg237*) was demonstrated. After considering the risk-benefit ratio, we decided to start zonisamide treatment. The dose was titrated gradually to 300 mg/d over 6 weeks. Myoclonus- and dystonia-specific tests demonstrated significant improvement compared to the pre-treatment status. The aim of this case report is to draw attention to this rare condition, its treatment and the importance of collaboration between medical subspecialties. Orv Hetil. 2019; 160(34): 1353–1357.

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NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement

Cited by 14 publications

References 15 publications

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

Zonisamidkezelés myoclonusdystoniában

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