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Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias (EDs), the molecular basis of many of these disorders remains unknown. In the present study, we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism, scalp hypotrichosis and hypodontia. Using whole exome sequencing, we identified 2 frameshift and 2 missense mutations in TSPEAR segregating with the disease phenotype in 3 families. TSPEAR encodes the thrombospondin-type laminin G domain and EAR repeats (TSPEAR) protein, whose function is poorly understood. TSPEAR knock-down resulted in altered expression of genes known to be regulated by NOTCH and to be involved in murine hair and tooth development. Pathway analysis confirmed that down-regulation of TSPEAR in keratinocytes is likely to affect Notch signaling. Accordingly, using a luciferase-based reporter assay, we showed that TSPEAR knock-down is associated with decreased Notch signaling. In addition, NOTCH1 protein expression was reduced in patient scalp skin. Moreover, TSPEAR silencing in mouse hair follicle organ cultures was found to induce apoptosis in follicular epithelial cells, resulting in decreased hair bulb diameter. Collectively, these observations indicate that TSPEAR plays a critical, previously unrecognized role in human tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway.

Delayed‐onset T‐cell‐mediated cutaneous adverse drug reactions are an uncommon but potentially serious result of medication exposures. Identification of culprit medications is crucial, but clinical diagnosis is often difficult. Patch tests and interferon‐gamma release assays (IFNγ‐RA) were previously reported as potentially useful ancillary tests, while rechallenges remain the reference standard test. We compared the number of positive test results with patch testing and IFNγ‐RA for drugs implicated as possible causes of cutaneous reactions. Fifty‐one patients with a suspected cutaneous drug eruption underwent patch testing and IFNγ‐RA for suspected drugs. Participants were followed up at least 9 months after the onset of the rash with results compared with the clinical diagnosis. Forty‐two patients presented with morbilliform/eczematous eruptions; five were diagnosed with fixed drug eruption (FDE) and four with erythema multiforme. None had positive patch testing to the drugs tested. A total of 8/51 (15.6%) patients had positive reaction by the IFNγ‐RA, and an additional 11 (21.6%) patients had borderline results. Positive or borderline results were more likely in patients with FDE (80%) than morbilliform/eczematous eruptions (30.9%) or erythema multiforme (25%). Our study emphasizes the necessity of additional effective ancillary tests in the evaluation of drug eruptions and supports the use of IFNγ‐RA for drug testing as a tool for identifying medications associated with cutaneous drug eruptions. [ABSTRACT FROM AUTHOR]

Objective: Management of a patient presenting with a first seizure depends on the risk of additional seizures. In clinical practice, the recurrence risk is estimated by the treating physician using the neurological examination, brain imaging, a thorough history for risk factors, and routine scalp electroencephalogram (EEG) to detect abnormal epileptiform activity. The decision to use antiseizure medication can be challenging when objective findings are missing. There is a need for new biomarkers to better diagnose epilepsy following a first seizure. Recently, an EEG‐based novel analytical method was reported to detect paroxysmal slowing in the cortical network of patients with epilepsy. The aim of our study is to test this method's sensitivity and specificity to predict epilepsy following a first seizure. Methods: We analyzed interictal EEGs of 70 patients admitted to the emergency department of a tertiary referral center after a first seizure. Clinical data from a follow‐up period of at least 18 months were available. EEGs of 30 healthy controls were also analyzed and included. For each EEG, we applied an automated algorithm to detect paroxysmal slow wave events (PSWEs). Results: Of patients presenting with a first seizure, 40% had at least one additional recurring seizure and were diagnosed with epilepsy. Sixty percent did not report additional seizures. A significantly higher occurrence of PSWEs was detected in the first interictal EEG test of those patients who were eventually diagnosed with epilepsy. Conducting the EEG test within 72 h after the first seizure significantly increased the likelihood of detecting PSWEs and the predictive value for epilepsy up to 82%. Significance: The quantification of PSWEs by an automated algorithm can predict epilepsy and help the neurologist in evaluating a patient with a first seizure. [ABSTRACT FROM AUTHOR]

Segmental pigmentation disorder (SPD) is characterized by hypo- or hyper-pigmented patches segmentally distributed, present in infancy, more prominently in darker-skinned children. The aim of this study was to define the demographic and clinical characteristics of SPD in a large series of patients. This was a retrospective case-control study at 2 paediatric dermatology centres in Israel. Data were collected through a telephone questionnaire and medical records. The study group consisted of 144 individuals with SPD and 144 individuals visiting the same institutions matched for age and sex. Median age of onset of SPD was near birth; 51% of patients were Sephardic Jews, and patients were followed up for a median period of 27 years. The patches were located on the torso (43%), mostly hypopigmented (52%), and remained of the same intensity and size in 55% and 41% of cases, accordingly. No differences in extracutaneous morbidities were found between SPD and control patients. This study delineates the demographic and clinical characteristics of SPD, confirms that cutaneous findings in SPD are more prominent in darker skin, tends not to expand in size or accentuate throughout the years, nor to be associated with extracutaneous morbidities. [ABSTRACT FROM AUTHOR]