In recent years, analyses of event related potentials/fields have moved from the selection of a few components and peaks to a mass-univariate approach in which the whole data space is analyzed. Such ...extensive testing increases the number of false positives and correction for multiple comparisons is needed.
Here we review all cluster-based correction for multiple comparison methods (cluster-height, cluster-size, cluster-mass, and threshold free cluster enhancement - TFCE), in conjunction with two computational approaches (permutation and bootstrap).
Data driven Monte-Carlo simulations comparing two conditions within subjects (two sample Student's t-test) showed that, on average, all cluster-based methods using permutation or bootstrap alike control well the family-wise error rate (FWER), with a few caveats.
(i) A minimum of 800 iterations are necessary to obtain stable results; (ii) below 50 trials, bootstrap methods are too conservative; (iii) for low critical family-wise error rates (e.g. p=1%), permutations can be too liberal; (iv) TFCE controls best the type 1 error rate with an attenuated extent parameter (i.e. power<1).
► Two contrasted cases of young adults with developmental dyslexia. ► Dissociation between phonological and visual attention span disorders. ► Cerebral activations recorded under fMRI and compared to ...skilled readers. ► Evidence of a double dissociation at both the cognitive and neurobiological level. ► Heterogeneity of developmental dyslexia.
A dissociation between phonological and visual attention (VA) span disorders has been reported in dyslexic children. This study investigates whether this cognitively-based dissociation has a neurobiological counterpart through the investigation of two cases of developmental dyslexia. LL showed a phonological disorder but preserved VA span whereas FG exhibited the reverse pattern. During a phonological rhyme judgement task, LL showed decreased activation of the left inferior frontal gyrus whereas this region was activated at the level of the controls in FG. Conversely, during a visual categorization task, FG demonstrated decreased activation of the parietal lobules whereas these regions were activated in LL as in the controls. These contrasted patterns of brain activation thus mirror the cognitive disorders’ dissociation. These findings provide the first evidence for an association between distinct brain mechanisms and distinct cognitive deficits in developmental dyslexia, emphasizing the importance of taking into account the heterogeneity of the reading disorder.
T1 mapping constitutes a quantitative MRI technique finding significant application in brain imaging. It allows evaluation of contrast uptake, blood perfusion, volume, providing a more specific ...biomarker of disease progression compared to conventional T1-weighted images. While there are many techniques for T1-mapping there is a wide range of reported T1-values in tissues, raising the issue of protocols reproducibility and standardization. The gold standard for obtaining T1-maps is based on acquiring IR-SE sequence. Widely used alternative sequences are IR-SE-EPI, VFA (DESPOT), DESPOT-HIFI and MP2RAGE that speed up scanning and fitting procedures. A custom MRI phantom was used to assess the reproducibility and accuracy of the different methods. All scans were performed using a 3T Siemens Prisma scanner. The acquired data processed using two different codes. The main difference was observed for VFA (DESPOT) which grossly overestimated T1 relaxation time by 214 ms 126 270 compared to the IR-SE sequence. MP2RAGE and DESPOT-HIFI sequences gave slightly shorter time than IR-SE (~20 to 30ms) and can be considered as alternative and time-efficient methods for acquiring accurate T1 maps of the human brain, while IR-SE-EPI gave identical result, at a cost of a lower image quality.
Summary
Background
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise.
Objectives
To describe the dermatological ...manifestations of NS, compare them with the literature findings, and test for dermatological phenotype–genotype correlations with or without the presence of PTPN11 mutations.
Methods
We performed a large 4‐year, prospective, multicentric, collaborative dermatological and genetic study.
Results
Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11‐NS, 34 patients with PTPN11‐NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11‐NS, present in 53·8% of patients. Multiple lentigines and café‐au‐lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations.
Conclusions
The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.
What's already known about this topic?
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and almost entirely without expert dermatological input.
A broad spectrum of dermatological findings is present in NS and better knowledge might help to define phenotype–genotype correlations and differentiate forms of NS from other RASopathies, specifically cardiofaciocutaneous syndrome.
What does this study add?
NS with PTPN11 mutations is usually associated with a mild and nonspecific cutaneous phenotype.
NS with multiple lentigines is typically associated with specific mutations of PTPN11 but atypical forms can be linked to RAF1 or NRAS mutations.
Absence of PTPN11 mutation in NS is associated with a higher frequency of keratinization disorders and hair abnormalities, the latter being commonly observed in cardiofaciocutaneous syndrome.
What is the translational message?
Abnormalities of the genes of the Ras–MAPK signalling pathway that are involved in NS underlie a spectrum of cutaneous manifestations including hair abnormalities, keratinization, pigmentary and connective tissue disorders and multiple melanocytic naevi.
This study adds new information to improve the definition of the cutaneous phenotype of NS and differentiate it phenotypically from RASopathies, specifically cardiofaciocutaneous syndrome and Costello syndrome.
Linked Comment: Carcavilla. Br J Dermatol 2019; 180:1293.
Plain language summary available online
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Summary
Background
Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification.
Objectives
To describe ...the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype–genotype correlations.
Methods
We performed a 4‐year, large, prospective, multicentric, collaborative dermatological and genetic study.
Results
Forty‐five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype–genotype correlation was determined.
Conclusions
A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.
What's already known about this topic?
Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological input.
Dermatological findings remain essential to diagnose CFCS and to differentiate it from other RASopathies that it resembles phenotypically, specifically Noonan syndrome (NS) and Costello syndrome (CS).
What does this study add?
Scarcity or absence of eyebrows, association of ulerythema ophryogenes and palmoplantar keratoderma, diffuse keratosis pilaris and multiple melanocytic naevi appeared pertinent manifestations in assisting the positive diagnosis of CFCS and differentiating it from CS and NS.
Oral acitretin could be highly beneficial for therapeutic management of PPHK.
No significant dermatological phenotype–genotype correlation in the presence or absence of BRAF mutation could be determined.
Linked Comment: Moss. Br J Dermatol 2019; 180:21.
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Dermatological manifestations in Noonan syndrome Bessis, D.; Miquel, J.; Bourrat, E. ...
British journal of dermatology (1951),
June 2019, 2019-06-00, 20190601, Volume:
180, Issue:
6
Journal Article
Peer reviewed
Open access
Summary
Noonan syndrome (NS) is a genetic disorder affecting up to 1 in 1000 people. It is recognised by an unusual facial appearance, heart defects and small stature. Some people with features of NS ...also have lots of small dark brown flecks on their skin (lentigines), a condition formerly known as LEOPARD syndrome but now called NS with multiple lentigines (NSML). There are also some atypical (unusual) “Noonan‐like” syndromes: this overlapping group of “Rasopathies” also includes Costello syndrome and cardio‐facio‐cutaneous syndrome. About 10 genes responsible for these conditions are now known, but the dermatological (skin) features of the different genetic types have never been clearly defined. Therefore, these French doctors, based at 10 different hospitals, systematically recorded the skin abnormalities seen in patients with any kind of NS attending their clinics over a 4‐year period, and correlated them with NS subtype and gene. Of 129 patients, aged from 9 months to 77 years, three quarters had mutations (changes) in the PTPN11 gene and of these 65 were diagnosed as NS and 34 as NSML. Dermatological features in the NS patients were mild and non‐specific such as easy bruising, raised hair follicles (keratosis pilaris), lax skin or wavy hair. NSML patients additionally had dozens of lentigines, larger brown patches and usually had particular PTPN11 mutations. NS patients with mutations in a different gene were more likely to have striking skin features including unusually curly hair, sparse eyebrows, marked keratosis pilaris or multiple moles. This research highlights the value of careful dermatological documentation in patients with genetic syndromes.
Linked Article: Bessis et al. Br J Dermatol 2019; 180:1438–1448
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