Effectiveness of a nurse-led one-to-one education programme in addition to standard care in children with atopic dermatitis: a multicentre randomized control trial.

BACKGROUND: Therapeutic patient education (TPE) is recommended for children with atopic dermatitis (AD), but no consensus has been reached on the optimal tailoring of delivery. While repeated multidisciplinary group education sessions have shown effectiveness, the benefits of one-on-one educational interventions led by nurses for children with AD have not yet been assessed. OBJECTIVES: To assess the benefits of additional, well-structured, 1-h nurse-led individual TPE interventions in children with AD and their families compared with standard care alone. METHODS: Children with moderate-to-severe AD and their parents were randomized to receive a 1-h nurse-led education session in addition to standard care vs. standard care alone. The primary outcome was the area under the curve (AUC) of the SCORing of Atopic Dermatitis index (SCORAD) from baseline to week 24 (lower AUC values represent better long-term control of the disease). RESULTS: In our study, 176 patients were randomized across 11 centres, and 153 were included in the full analysis set. The mean (SD) age was 4.47 (4.57) years. By week 24, there were no significant differences in the AUCs of the SCORAD between the two groups (P = 0.3). Secondary outcomes including patient-reported severity and quality of life [AUCs of the patient-oriented SCORAD (PO-SCORAD) and Infants' Dermatitis Quality of Life Index (IDLQI), Children's Dermatitis Quality of Life Index (CDLQI) and Family Dermatitis Quality of Life Index (FDLQI)] were not significantly different between the two groups. The only significant change observed in the intervention group, when compared with the one receiving standard care, was a decrease in topical steroid phobia, as assessed by the topical corticosteroid phobia (TOPICOP) score. Prespecified subgroup analyses showed that disease severity in the intervention group was significantly lower throughout the study, compared with the standard-care group when participants had moderate AD at baseline (n = 47); while participants with severe AD at baseline (n = 106) did not show benefit from the intervention. Participants showed no additional benefit from the intervention regardless of age group. CONCLUSIONS: This study did not show any additional effectiveness, in long-term severity control, of a 1-h nurse-led TPE intervention in children with AD treated with standard care, compared with those treated with standard care alone. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for patients in the subgroup with moderate AD.

Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing disease that affects 7­15% of children worldwide. Therapeutic patient education (TPE) is recommended for children with AD, but no agreement has been reached on the best way to tailor delivery. While repeated multidisciplinary group education sessions in a hospital setting have been found effective, this type of intervention requires a lot of resources and is time-consuming. To assess the benefits of TPE in children with AD, researchers in France carried out this study with children with moderate-to-severe AD, to compare a 1-hour nurse-led education session in addition to standard care vs. standard care alone. The main aim of this research was to assess the effectiveness of a TPE intervention over a period of 6 months, using a measurement tool called the SCORAD (SCORing of Atopic Dermatitis index). We found no additional benefits in terms of long-term severity control and quality of life at 6 months of a 1-hour nurse-led education intervention in children with AD treated with standard care. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for people in the moderate AD subgroup.

Validation of a dermatoscopy-based algorithm for the diagnosis of acral melanoma.

INTRODUCTION: Diagnosis of acral melanocytic lesions can be challenging. The BRAAFF checklist was introduced as a tool to help differentiate between acral nevi and melanoma but has not been validated. METHODS: We asked raters with varying expertise in dermatoscopy to diagnose dermatoscopic images of 533 acral nevi and 144 melanomas via an online platform with and without use of the BRAAFF checklist. From the ratings we calculated sensitivity, specificity, and interrater agreement. Additionally, a new simplified version of the checklist was also tested. RESULTS: We collected 6880 ratings from 175 readers. The BRAAFF checklist achieved a sensitivity of 92.5% and a specificity of 65.0%, which was similar to diagnosis from pattern recognition (sensitivity 90.0%, specificity: 72.1%). Interrater agreement for the BRAAFF criteria ranged from fair to moderate, with lowest agreement for parallel ridge and fibrillar pattern (alpha=0.31) and highest for asymmetry of colors and structures (alpha=0.46). Agreement and diagnostic accuracy were higher for more experienced readers. A simplified version with only two criteria achieved similar sensitivity (95.0%) and lower specificity (60.0%) as the original BRAAFF checklist. Conclusion: The BRAAFF checklist is a useful tool for the diagnosis of melanocytic acral lesions with acceptable sensitivity and reasonable specificity but is not superior to pattern recognition. A simplified version of the checklist could be easier to use with equal sensitivity while exhibiting a modest reduction in specificity.

Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. OBJECTIVES: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. METHODS: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). CONCLUSIONS AND RELEVANCE: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations.

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.

Effectiveness of biologic therapies in children with palmoplantar plaque psoriasis: An analysis of real-life data from the BiPe cohorts.

BACKGROUND: Palmoplantar plaque psoriasis is a frequent clinical subtype of childhood psoriasis. This study evaluated the effectiveness of biologic therapies in children with palmoplantar plaque psoriasis using data from the two Biological treatments for Pediatric Psoriasis (BiPe) cohorts. METHODS: Data for all 170 patients included in the BiPe cohorts were analyzed. Data on the effectiveness (PGA, PASI between baseline and 3 months of treatment) of biologic therapies were then compared between children with palmoplantar plaque psoriasis (n = 20) and those with generalized plaque psoriasis (n = 136). Clinical and demographic data were also analyzed. RESULTS: Children in the palmoplantar group were more likely to be male (p = .04), with an earlier age of psoriasis onset (p < .001), and more frequent nail involvement (p < .001). After 3 months of biologic treatment, mean PGA scores were higher in the palmoplantar group than in the generalized plaque psoriasis group (p = .004). In the palmoplantar group, continuation rates were higher for adalimumab than for etanercept or ustekinumab (p = .01). Primary inefficacy was a more frequent reason for stopping biologic therapies in the palmoplantar group (p = .01), and disease remission was less frequent (p = .05). Combined systemic and biologic therapies were more frequently used in palmoplantar plaque psoriasis (p < .001). CONCLUSIONS: This study demonstrated the treatment-resistant nature of palmoplantar plaque psoriasis and indicated that adalimumab could be the most effective biologic treatment. Larger studies are needed to allow therapeutic algorithms for palmoplantar plaque psoriasis to be proposed in pediatric psoriasis management guidelines.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Biologics combined with conventional systemic agents for the treatment of children with severe psoriasis. Real-life data from the BiPe cohorts and a practice survey among French and Italian pediatric dermatologists.

Combined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We evaluated the use of combinations of conventional systemic therapies and biologics in children with psoriasis in daily practice. This two-part study used data from the 170 children in the Franco-Italian BiPe cohorts to evaluate the use, efficacy, and safety of combined conventional systemic-biologic therapies, and from a survey carried out among French and Italian dermatologists to better understand the reasons for using or avoiding these combinations. In total, 33 children (19.4%) from 13 dermatology centers received 48 combined conventional systemic-biologic therapies (cumulative duration: 43.6 years), including three triple combination therapies (acitretin-methotrexate, with a TNF-alpha inhibitor). A total of 14 different combinations were used, most frequently etanercept-acitretin (n = 10), adalimumab-acitretin (n = 7), adalimumab-methotrexate (n = 5), and ustekinumab-methotrexate (n = 5). The combined therapies were started at biologic initiation in 41 cases (85.4%), and after a period of biologic monotherapy in the remaining 7 cases. Mean PGA and PASI scores decreased between baseline and M3 with all the combinations used. Four serious adverse events were reported, all with favorable outcomes. The survey was completed by 61 dermatologists: 39 (63.9%) had previously used or planned to use the combined therapies, most commonly TNF-alpha inhibitors with acitretin or methotrexate. The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. Combined therapies have been used frequently in the treatment of childhood psoriasis, in a range of clinical situations and in variable drug combinations, without significant toxicity. Although the use of these combined therapies needs to be clarified in future management guidelines, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis, and recalcitrant disease.

Perialar intertrigo in children and adolescents: A multicenter prospective study of 41 cases.

BACKGROUND/OBJECTIVES: We observed isolated cases of perialar intertrigo in children and teenagers that did not appear to correspond to any known clinical entity. The objective of this study was to describe the clinical features of this dermatosis and the clinical characteristics of the patients. METHODS: We conducted a prospective, multicenter cohort study in France from August 2017 to November 2019. All the patients under 18 years of age with chronic perinasal intertrigo were included. A standardized questionnaire detailing the clinical characteristics of the patients and the description of the intertrigo. If possible, a Wood's lamp examination of the intertrigo was done. RESULTS: Forty-one patients were included (25 boys and 16 girls, average age: 12.1 years). Intertrigo was bilateral in 38 patients (93%). The majority of patients had no symptoms (54%). Pruritus was present in 39% of cases. Orange red follicular fluorescence was present in the perialar region on Wood's light examination in 78% of cases with active fluorescence. The presumptive diagnoses suggested by the investigators were acne (24.4%), seborrheic dermatitis (19.5%), rosacea (9.8%), psoriasis (9.8%) and perioral dermatitis (7.3%). No diagnosis was proposed in 22% of the cases. CONCLUSIONS: We describe a previously undescribed clinical sign which is characterized by a chronic bilateral erythematous intertrigo located in the perialar region. It can be isolated or associated with various facial dermatoses.

Switching biologics in children with psoriasis: Results from the BiPe cohort.

BACKGROUND: There is currently little information on switching biologics in pediatric psoriasis. OBJECTIVE: To evaluate the real-world clinical practice and safety of switching biologics in the "Biological Treatments for Pediatric Psoriasis" (BiPe) cohort. METHODS: Data for all 134 patients included in the BiPe cohort were analyzed. A further evaluation of the subpopulation of patients who switched from a first-line biologic to a second-line biologic was then conducted. Drug survival rates were also compared between biologics given as first-line or second-line agents. RESULTS: Overall, 29 patients (female: 55%; mean age: 16.6 ± 3.0 years) switched between two biologics. Etanercept (ETN) was the first-line biologic used in 23 patients: 16 (69.6%) switched to adalimumab (ADA) and seven (30.4%) to ustekinumab (UST). Six patients received first-line ADA and switched to UST. Loss of efficacy (62.1%), primary inefficacy (20.7%), and parental choice (6.9%) were the main reasons for switching biologics. One (3.4%) of the switches was performed because of adverse events or intolerance. For UST and ADA, the 18-month drug survival rate did not differ according to whether the agent was given as a first-line or second-line biologic (UST: P = .24; ADA: P = .68). No significant differences in drug survival rates were observed between the three different switches (ADA to UST, ETN to ADA, and ETN to UST). CONCLUSION: Our study provided key insights into the real-life clinical practice of switching biologics in pediatric psoriasis patients. However, more information and guidance on switching biologics in pediatric psoriasis are needed to improve real-life practice and outcomes.

Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. METHODS: Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. RESULTS: Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently. CONCLUSION: This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk-benefit evaluations for sirolimus treatment in PROS.

Clinical Profile of Methotrexate-resistant Juvenile Localised Scleroderma.

Methotrexate has demonstrated its efficiency for the treatment of juvenile localized scleroderma but some patients may be resistant. The aim of our study was to define the profile of such patients. We performed an observational retrospective multicenter study between 2007 and 2016 and included all children seen in the French Paediatric Dermatology and Rheumatology departments with active localized scleroderma treated by methotrexate for a minimum of 4 months. Metho-trexate efficacy was assessed clinically and/or by imaging between the fourth to twelfth months of treatment. A total of 57 patients were included. Metho-trexate dosage ranged from 7 to 15 mg/m2/week. Only 4 patients were resistant. No common features could be identified between these 4 patients. Children with localized scleroderma are rarely resistant to metho-trexate and we did not identify a clinical profile for those resistant patients.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Prevalence of Nail Scabies: A French Prospective Multicenter Study.

INTRODUCTION: To assess the prevalence of nail involvement in children <16 years old with a confirmed diagnosis of scabies. STUDY DESIGN: Observational, prospective study in 7 French dermatology departments between June 2015 and January 2017. Children were included if they had scabies confirmed by dermoscopy and/or microscopy and if nails could be sampled. The first toenails and thumbnails as well as clinically affected nails were systematically sampled for microscopic examination. Individual data were recorded via a standardized questionnaire. RESULTS: A total of 47 children with scabies were included (26 females [55.3%], mean age 3.6 ± 4.0 years). Pruritus was present in 42 children (89.3%); the relapse rate was 38.3% (n = 18). In 3 infants (6.4%), Sarcoptes mites were revealed by dermoscopy or microscopy of the first toenails (2 cases) and a thumbnail (1 case), but nails were normal in 2 children. Two of the 3 infants had already received treatment for scabies in the previous weeks. CONCLUSION: Prevalence of nail involvement in children with confirmed scabies was 6.4%. Nails should not be overlooked during scabies treatment.

Clinical and dermoscopic characterization of pediatric and adolescent melanomas: Multicenter study of 52 cases.

BACKGROUND: Knowledge regarding the morphologic spectrum of pediatric melanoma (PM) is sparse, and this may in part contribute to delay in detection and thicker tumors. OBJECTIVE: To analyze the clinicodermoscopic characteristics of PM. METHODS: Retrospective study of 52 melanomas diagnosed in patients before the age of 20 years. RESULTS: On the basis of its clinical, dermoscopic, and histopathologic characteristics, PM can be classified as spitzoid or nonspitzoid. The nonspitzoid melanomas (n = 37 [72.3%]) presented in patients with a mean age of 16.3 years (range, 8-20) and were associated with a high-risk phenotype and a pre-existing nevus (62.2%). The spitzoid melanomas (n = 15 [27.7%]) were diagnosed in patients at a mean age of 12.5 years (range, 2-19) and were mostly de novo lesions (73.3%) located on the limbs (73.3%). Whereas less than 25% of PMs fulfilled the modified clinical ABCD criteria (amelanotic, bleeding bump, color uniformity, de novo at any diameter), 40% of spitzoid melanomas did. Dermoscopic melanoma criteria were found in all cases. Nonspitzoid melanomas tended to be multicomponent (58.3%) or have nevus-like (25%) dermoscopic patterns. Spitzoid melanomas revealed atypical vascular patterns with shiny white lines (46.2%) or an atypical pigmented spitzoid pattern (30.8%). There was good correlation between spitzoid subtype histopathologically and dermoscopically (κ = 0.66). LIMITATIONS: A retrospective study without re-review of pathologic findings. CONCLUSION: Dermoscopy in addition to conventional and modified clinical ABCD criteria helps in detecting PM. Dermoscopy assists in differentiating spitzoid from nonspitzoid melanomas.

Management of childhood psoriasis in France. A national survey among general practitioners, pediatricians, and dermatologists.

Psoriasis affects 0.5-2% of children. Severe forms required use of systemic treatments. Few studies are published on efficiency and tolerance of systemic treatments in children. We conducted a survey in France to better understand management of children with psoriasis. A survey on childhood psoriasis management was sent by e-mail to GPs, pediatricians, and dermatologists. The survey included 384 physicians. Respectively 53.1%, 49.8%, and 83.3% of GPs, pediatricians, and dermatologists declare to have seen at least one child with psoriasis during the 3 previous months. Less than 5% of GPs and pediatricians used severity score versus 23.7% of dermatologists. If most of physicians declare to use local treatments, less than 5% of GPs and pediatricians used systemic treatments. 32.4% of dermatologists declared to use at least one systemic treatment, but only 2.9% to use the 4 systemic treatments available in France. This survey shows that only half of GPs and pediatricians see children with psoriasis, but most of dermatologists. However, the management of severe forms seems limited by the underuse of severity scores and systemic treatments. These results should stimulate dermatology societies to promote prospective studies and guidelines in young populations with psoriasis.

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.

PURPOSE: Postzygotic activating mutations of PIK3CA cause a wide range of mosaic disorders collectively referred to as PIK3CA-related overgrowth spectrum (PROS). We describe the diagnostic yield and characteristics of PIK3CA sequencing in PROS. METHODS: We performed ultradeep next-generation sequencing (NGS) of PIK3CA in various tissues from 162 patients referred to our clinical laboratory and assessed diagnostic yield by phenotype and tissue tested. RESULTS: We identified disease-causing mutations in 66.7% (108/162) of patients, with mutant allele levels as low as 1%. The diagnostic rate was higher (74%) in syndromic than in isolated cases (35.5%; P = 9.03 × 10-5). We identified 40 different mutations and found strong oncogenic mutations more frequently in patients without brain overgrowth (50.6%) than in those with brain overgrowth (15.2%; P = 0.00055). Mutant allele levels were higher in skin and overgrown tissues than in blood and buccal samples (P = 3.9 × 10-25), regardless of the phenotype. CONCLUSION: Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions.Genet Med advance online publication 02 February 2017.

Congenital Cases of Concomitant Harlequin and Horner Syndromes.

We report three pediatric cases of concomitant congenital Horner and Harlequin syndromes. This association suggests a lesion at the superior cervical ganglion or just inferior. Often, no underlying lesion is documented.

The scalp hair collar and tuft signs: A retrospective multicenter study of 78 patients with a systematic review of the literature.

BACKGROUND: Hair collar sign (HCS) and hair tuft of the scalp (HTS) are cutaneous signs of an underlying neuroectodermal defect, but most available data are based on case reports. OBJECTIVE: We sought to define the clinical spectrum of HCS and HTS, clarify the risk for underlying neurovascular anomalies, and provide imaging recommendations. METHODS: A 10-year multicenter retrospective and prospective analysis of clinical, radiologic, and histopathologic features of HCS and HTS in pediatric patients was performed. RESULTS: Of the 78 patients included in the study, 56 underwent cranial and brain imaging. Twenty-three of the 56 patients (41%) had abnormal findings, including the following: (1) cranial/bone defect (30.4%), with direct communication with the central nervous system in 28.6%; (2) venous malformations (25%); or (3) central nervous system abnormalities (12.5%). Meningeal heterotopia in 34.6% (9/26) was the most common neuroectodermal association. Sinus pericranii, paraganglioma, and combined nevus were also identified. LIMITATIONS: The partial retrospective design and predominant recruitment from the dermatology department are limitations of this study. CONCLUSIONS: Infants with HCS or HTS are at high risk for underlying neurovascular anomalies. Magnetic resonance imaging scans should be performed in order to refer the infant to the appropriate specialist for management.