Therapeutic inertia during isotretinoin treatment of juvenile acne by dermatologists, paediatricians and general practitioners.

BACKGROUND: Isotretinoin is an effective treatment for severe juvenile acne, but it appears to be underused in relation to the recommendations. Therapeutic inertia is defined as a failure to initiate or intensify treatment even when warranted by the recommendations. The aim of this study was to investigate therapeutic inertia among dermatologists (D), paediatricians (P), and general practitioners (GPs) in initiating isotretinoin for moderate-to-very severe juvenile acne. METHODS: Data were collected using a questionnaire distributed to French physicians through medical societies via Internet. The questions explored the role in inertia of factors related to physicians, patients, parents, and the healthcare system, and evaluated barriers and facilitators to prescribing isotretinoin. RESULTS: In all, 768 physicians responded to the survey (528 D, 178P, and 61 GPs; mean age: 51 years; women: 78 %). Their responses revealed that 99 % of dermatologists felt comfortable prescribing isotretinoin, compared with 8 % and 15 % of paediatricians and GPs (p < 0.05); 93 % of dermatologists were aware of the current guidelines compared with 37 % of paediatricians and GPs. Under 50 % of the physicians had received training on acne in the previous 3 years, regardless of specialty. The most frequently identified factors for inertia were concerns over the psychological consequences of the treatment in adolescents, exclusive requests from parents, and patient unavailability. Paediatricians reported having insufficient knowledge of current recommendations, a lack of training, and a tendency to anticipate poor compliance. Paediatricians and GPs considered that access to first-time prescriptions and peer-to-peer exchanges would constitute facilitating factors in their use of isotretinoin. DISCUSSION: Concerns over the psychiatric consequences of isotretinoin in adolescents, the need for frequent follow-up, and lack of continuing medical education were identified as factors favouring inertia in the initiation of isotretinoin treatment in patients with moderate-to-very severe juvenile acne, particularly among paediatricians and GPs. Potential strategies to overcome these barriers include regular training, simplified recommendations in French, and access to first-time prescription for paediatricians and GPs.

Traditional healers or bonesetters ("rebouteux") in France: A survey of their practice, profile, and customers.

BACKGROUND: In France, many people consult "bonesetters" for several medical reasons. Little is known about them. We aimed to investigate the practices of traditional healers in France as well as their profile and that of their customers. METHODS: This was a survey carried out in Metropolitan France. A 33-item questionnaire developed by a multidisciplinary group was sent to a sample of 148 traditional healers found on the Internet and by word of mouth. RESULTS: Of the 148 questionnaires sent, 89 (60.1 %) were returned and 67 (45.3 %) were analyzed: 51.5 % (n = 34) of respondents were men, and the mean (±standard deviation) age was 51.6 ±â€¯11.6 years. The respondents considered that they had received a gift of healing and were mainly magnetic healers (68.2 %). They became aware of this gift at a mean age of 19.9 ±â€¯14.1 years. The traditional healers practiced mainly in rural areas (54.5 %), at home (59.1 %), and used their hands to transmit energy (95.5 %). They advertised their practice mainly by word of mouth (89.4 %) and had a predominantly female clientele (78.1 %). Various diseases were treated, with the most frequent being subjective complaints (pain, stress, fatigue, insomnia) and dermatological complaints (eczema, accidental and post-herpes-zoster burns, psoriasis, and warts). Most respondents considered their activities to be complementary to conventional medicine, and 10.9 % considered them more effective. Some indicated that they did not consider themselves "healers" but rather "providers of relief". DISCUSSION: The results of this survey provide a better understanding of this network of local care that revolves around medicine.

Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014-2021 French Ouest DataHub.

BACKGROUND: The factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. OBJECTIVES: To identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. METHODS: We performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. RESULTS: A total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0-78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02-0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. CONCLUSION: The risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Healthcare transition from childhood to adulthood in pseudoxanthoma elasticum: Patient experience and recommendations for health practitioners.

PURPOSE: Health-care transition (HCT) is a necessary part of the care process for allsick adolescents, to allow their empowerment while limiting disruption to follow-up care. Pseudoxanthoma elasticum (PXE) runs the risk of losing patients to follow-up because young patients are predominantly asymptomatic. This can be detrimental as it can prevent primary prevention measures from being properly implemented. The purpose of this study was to assess satisfaction of PXE patients with their health-care transition and to identify the factors associated with its success, in order to improve care management in young PXE patients. METHODS: Patients aged 22 to 40 years diagnosed with PXE before the age of 16 years were included from the cohort of patients followed at Angers University Hospital. They were sent a questionnaire for the purposes of collecting data on medical management during adolescence, transition and adulthood. RESULTS: Eleven responses were obtained from the 21 patients surveyed. The median satisfaction score of PXE patients regarding their transition was 5/10. Three patients reported having discontinued follow-up after transition. In adulthood, the majority of the participants were followed up by 4 specialists as recommended. It was incumbent on 50% of the patients who changed doctors to provide details of their own medical history to the new practitioner. CONCLUSION: Better intra-practitioner communication and a chart summarizing the principles of primary prevention, optimal follow-up care and its frequency are simple to implement and in all likelihood result in better health-care transition for young PXE patients.

Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.

PURPOSE: PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. METHODS: Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. RESULTS: Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort (n = 6). No significant reduction in affected tissue volume was observed (mean -4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). CONCLUSION: Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.

Skin manifestations of COVID-19 in children: Part 3.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions, and in Part 2 we expanded to other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In this part of the review, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

Skin manifestations of COVID-19 in children: Part 2.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

Skin manifestations of COVID-19 in children: Part 1.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discuss one of the first and most widespread cutaneous manifestation of COVID-19, chilblain-like lesions. In Part 2, we review other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome, while in Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children, for both COVID-19 and any other pre-existing conditions.

Specific features of amoxicillin-associated Drug Reaction with Eosinophilia and Systemic Symptoms syndrome: a nationwide study.

BACKGROUND: Growing evidence indicates that amoxicillin induces herpesvirus replication in vitro. As these play a central pathophysiological role in Drug Reaction with Eosinophilia and Systemic Symptoms syndrome (DRESS), amoxicillin could present with specific DRESS features. OBJECTIVE: To characterize the onset patterns of amoxicillin-associated DRESS. METHODS: All cases of DRESS (Kardaun score ≥4) involving amoxicillin and reported in the French Pharmacovigilance Database between January 1, 2004 and November 30, 2019 were included. Onset circumstances for these cases were categorized considering the onset delay from amoxicillin initiation, and the presence of concomitant medications with a compatible time to onset. RESULTS: A total of 146 probable cases or definite cases of DRESS were included. Three onset circumstances were identified: (i) 'amoxicillin clear culprit' where amoxicillin was the sole suspect drug or when concomitant drugs of compatible time to onset were not reported to cause DRESS (n = 62); (ii) 'amoxicillin possible culprit' in the presence of other potentially culprit drugs in addition to amoxicillin (n = 44) and (iii) 'flare' where amoxicillin, used after DRESS onset, induced flare-up reactions (n = 40). The median time to onset was 5 days (IQR 2-11) in 'clear culprit', and 18 days (IQR 7-26) in 'possible culprit' cases. In 'flare' cases, the median latency between amoxicillin initiation and flare-up reactions was 3 days (IQR 2-5). CONCLUSIONS: Amoxicillin can induce DRESS with a specific early onset and exacerbate DRESS from another drug.

Factors influencing quality of life in children with low-flow vascular malformations: a qualitative study using focus groups.

BACKGROUND: Very few studies have evaluated the quality of life (QoL) of children suffering from low-flow vascular malformations. This is the first study investigating the influencing factors. OBJECTIVES: To identify the factors influencing QoL in children with low-flow vascular malformations. METHODS: We conducted a qualitative study employing focus group interviews (Clinical Trials Number: NCT03440827). The study was a prospective, interventional, non-comparative, multicentre study performed in four expert centres for vascular anomalies. Qualitative data about personal experiences, feelings, difficulties, needs and various factors influencing behaviours were collected. Theme-based content analysis (manual and specialist textural software guided) were used to analyse the verbatim transcripts of all focus group sessions. Manual qualitative discourse analysis was performed to identify the different themes and categories. Informatics' analyses were subsequently performed for each individual category. RESULTS: Ten focus groups (26 individuals including 10 children aged 11 to 15 years) were conducted until saturation. Influencing factors were related to 4 categories: medical care, self-image, social impact on daily activities and challenging social relationships. These factors were responsible for intrafamily upheavals and may lead to future identity-building problems. CONCLUSIONS: This study provides an essential framework from which physicians can develop strategies to improve patient care and quality of life. These data may also be useful to develop specific age-sensitive QoL questionnaires.

Impact of the COVID-19 pandemic on children with psoriasis.

BACKGROUND: Children with psoriasis may have been directly impacted by the COVID-19 pandemic and their illness may also have affected their ability to follow preventive measures. OBJECTIVE: To investigate the impact of the COVID-19 pandemic on children with psoriasis. METHODS: A survey of children (<18 years) with psoriasis, conducted from June 10 to June 29, 2020. RESULTS: In total, 92 children were included: 71.7% had psoriasis lesions at the time of home lockdown while 45.2% were receiving systemic treatments, and two contracted COVID-19. During lockdown, psoriasis worsened in 47.3% of the children and 18.8% stopped their systemic treatments, mainly for reasons linked to the pandemic. A total of 41.3% had a consultation for psoriasis during lockdown (71.1% by teleconsultation): 39.5% due to worsening of their psoriasis and 21.1% for pandemic-related issues. Among patients not having a consultation during lockdown, 27.5% had a cancellation by the doctor and 9.3% had concerns over going to see the doctor. Finally, 22.8% of patients reported finding it difficult to respect hygiene measures because of their psoriasis, e.g., application of alcohol-based hand sanitizers (47.6%), handwashing routines (42.9%), and wearing a mask (28.6%). CONCLUSIONS: This study demonstrates the major clinical impact of the COVID-19 pandemic on children with psoriasis. Teleconsultations played a key role in patient management as regards patient monitoring, provision of information, and renewal of treatments. It is vital that we learn from these data to improve and adapt the monitoring of chronic dermatoses in both children and adults in the event of a future health crisis.

Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters.

BACKGROUND: A marked increase in frequency of acute acral eruptions (AAE) was observed in children during the COVID-19 pandemic in the spring period. OBJECTIVES: In this observational multicenter study, based on children with AAE, we aimed to assess the proportion of household members possibly infected by SARS-CoV-2. METHODS: We collected data from all children observed with AAE, prospectively from April 7, 2020 to June 22, 2020, and retrospectively since February 28, 2020. The primary outcome was the household infection rate, defined as the proportion of family clusters having at least one member with COVID-19 infection other than the child with AAE ("index child"). The definition of a case was based on characteristic clinical signs and a positive PCR or serology. RESULTS: The study included 103 children in 10 French departments and in Quebec. The median age was 13 years and the interquartile range [8-15], with a female-to-male ratio of 1/1.15. In children with AAE, all PCR tests were negative (n=18), and serology was positive in 2/14 (14.3%) cases. We found no significant anomalies in the lab results. A total of 66 of the 103 families (64.1%) of included children had at least one other infected member apart from the index child. The total number of household members was 292, of whom 119 (40.8%) were considered possibly infected by SARS-CoV-2. No index children or households exhibited severe COVID-19. DISCUSSION: Among the 103 households included, 64.1% had at least one infected member. Neither children with AAE nor their households showed severe COVID-19.

Ivermectin safety in infants and children under 15 kg treated for scabies: a multicentric observational study.

BACKGROUND: Scabies is a frequent condition seen in infants and children. Only topical treatments have been approved in infants, but some of them are poorly tolerated. Oral ivermectin is approved for the treatment of scabies in several countries, but its use in infants and children weighing < 15 kg is off label. OBJECTIVES: To assess the safety of ivermectin in infants and young children, and to collect data on ivermectin efficacy in these age groups. METHODS: This study was performed in the dermatology and paediatric dermatology departments of 28 French centres between July 2012 and November 2015. Physicians treating an infant or child weighing < 15 kg for scabies with oral ivermectin were asked to send back a completed standardized and anonymous questionnaire, and the data were analysed. RESULTS: Data were collected on 170 infants and children aged 1-64 months, with a body weight of 4-14·5 kg, who were treated with oral ivermectin. The mean dose received was 223 µg kg-1 and 89% of the patients received a systematic second dose. Concomitant topical treatment was administered to 73% of patients. Adverse events were reported in seven patients (4%) and were not severe. At the follow-up visit, 139 (85%) patients had achieved healing. Factors significantly associated with healing were an ivermectin dose > 200 µg kg-1 (P < 0·001), and a delay between those two doses of < 10 days (P = 0·025). CONCLUSIONS: Our findings suggest the safety and efficacy of ivermectin for the treatment of scabies in infants and young children. What's already known about this topic? Scabies is a frequent condition in small children and infants, but the therapeutic options are limited. Ivermectin has been approved for the treatment of scabies in adults and children > 15 kg, but its use is off-label in infants and children weighing < 15 kg. Safety data on the use of ivermectin in children weighing < 15 kg are limited. What does this study add? Of 170 infants and children weighing < 15 kg who were treated for scabies with oral ivermectin, there were only seven reported mild adverse events and no serious ones. Our results show that ivermectin is effective in treating scabies in 85% of patients. Efficacy is higher when the received dose exceeds 200 µg kg-1 and when the delay between the two doses is < 10 days. Respond to this article.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder.

NR4A2, a member of the nuclear receptor superfamily, is involved in modulation of target gene transcription, regulating several developmental processes such as regulation of cellular homeostasis, neuronal development, inflammation and carcinogenesis. 2q24.1 deletions are extremely rare, and only 1 patient with a de novo deletion encompassing only NR4A2 gene was reported so far. We report 3 additional patients with a de novo deletion encompassing NR4A2: 2 patients have deletions encompassing only NR4A2 gene and 1 patient has a deletion including NR4A2 and the first exon of GPD2. Our patients presented a neurodevelopmental disorder including language impairment, developmental delay, intellectual disability and/or autism spectrum disorder. We suggest that NR4A2 haploinsufficiency is implicated in neurodevelopmental disorder with high penetrance.

CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.

Clinical and haemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations: data from the national paediatric French cohort CONAPE.

BACKGROUND: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. OBJECTIVES: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. METHODS: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2-12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. RESULTS: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. CONCLUSIONS: ABF measured by Duplex ultrasonography is a simple, low-cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated.

Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective study.

OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.