Biallelic variants in RNU12 cause CDAGS syndrome.

CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.

Influence of hair oil on scalp fungal cultures.

It has been clinically speculated that the use of oil for hair grooming may change detection of fungus on culture; however, the effect of hair oil on fungal cultures remains poorly studied. In this prospective case-controlled study, scalp cultures were collected from twenty-eight pediatric patients with clinically suspected tinea capitis before and after cosmetic hair oil was rubbed into the scalp. Following hair oil application, fifteen of the sixteen originally positive patients tested positive, while one patient that had tested negative prior to hair oil had a positive culture. Our study suggests that recent hair oil application has minimal effect on the sensitivity of fungal culture for tinea capitis and we can rely on our standard fungal cultures with or without hair oil.

Tiled array-based sequencing identifies enrichment of loss-of-function variants in the highly homologous filaggrin gene in African-American children with severe atopic dermatitis.

Filaggrin (FLG) loss-of-function (LOF) variants are a major risk factor for the common inflammatory skin disease, atopic dermatitis (AD) and are often population-specific. African-American (AA) children are disproportionately affected with AD, often later developing asthma and/or allergic rhinitis and comprise an atopy health disparity group for which the role of FLG LOF is not well known. Discovery of FLG LOF using exome sequencing is challenging given the known difficulties for accurate short-read alignment to FLG's high homology repeat variation. Here, we employed an array-based sequencing approach to tile across each FLG repeat and discover FLG LOF in a well-characterized cohort of AA children with moderate-to-severe AD. Five FLG LOF were identified in 23% of our cohort. Two novel FLG LOF singletons, c.488delG and p.S3101*, were discovered as well as p.R501*, p.R826* and p.S3316* previously reported for AD. p.S3316* (rs149484917) is likely an African ancestral FLG LOF, reported in African individuals in ExAC (Exome Aggregation Consortium), Exome Variant Server (ESP), and 4 African 1000G population databases (ESN, MSL, ASW, and ACB). The proportion of FLG LOF (11.5%) among the total FLG alleles in our cohort was significantly higher in comparisons with FLG LOF reported for African individuals in ExAC (2.5%; P = 4.3 × 10-4 ) and ESP (1.7%; P = 3.5 × 10-5 ) suggesting a disease-enrichment effect for FLG LOF. Our results demonstrate the utility of array-based sequencing in discovering FLG LOF, including novel and population-specific, which are of higher prevalence in our AA severe AD group than previously reported.

Skin cancer risk education in pediatric solid organ transplant patients: an evaluation of knowledge, behavior, and perceptions over time.

Skin cancer risk is elevated in solid OTRs. Studies of skin cancer awareness and sun-protection behaviors in pOTRs have not been reported. We measured effects over time of a multimodal educational intervention on knowledge of sun-protection practices and skin cancer risk, engagement in sun-protection behaviors, and self-efficacy and perceived barriers to photoprotection in pOTRs, their guardians, and a comparison group of children and guardians. Knowledge about skin cancer risk increased in pOTRs and their guardians (P≤.01) and frequency of pOTRs' sun-protection behaviors reported by pOTRs and their guardians also improved.

Eccrine Angiomatous Hamartoma: A Clinicopathologic Review of 18 Cases.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is a benign cutaneous lesion defined by the proliferation of hamartomatous eccrine and capillary-like vascular elements in the dermis. However, the epidemiologic, morphologic, and histopathologic aspects of this uncommon disorder have yet to be fully delineated. METHODS: The authors retrospectively reviewed 18 EAH cases (including 14 accompanying skin biopsy specimens) diagnosed at 4 American university hospitals from 1996 to 2014. RESULTS: Patients ranged from 3 days to 84 years at time of diagnosis with a median age of 15 years. A male:female ratio of 11:7 was observed. Sixty-seven percent of cases presented in the extremities, but lesions in the trunk and head/neck regions also occurred. Four patients had multiple lesions, and 2 displayed a segmental pattern. Histologically, dermal vascular dilatation and acanthosis often accompanied EAH's typical eccrine and vascular comingling. One individual developed EAH at the site of a recurrent squamous cell carcinoma after previous excision. CONCLUSIONS: Although previously thought to occur primarily as a solitary angiomatous-appearing malformation on the extremities of children, EAH may develop with some frequency in adults and may manifest in a multifocal linear distribution. The authors also raise additional histopathologic consideration in support of the vascular theory of histogenesis for this condition.

Long-term follow-up of pediatric trachyonychia.

Pediatric trachyonychia is an acquired nail disease that can cause distress to families. It is a poorly understood disease, and long-term follow-up data are lacking. We present an institutional review of 11 children with isolated pediatric trachyonychia followed over time. Children with the diagnosis of pediatric trachyonychia were identified and invited to participate. Pictures were taken on follow-up and a questionnaire was answered. Exclusion criteria include having another diagnosis at the initial visit that causes nail dystrophy. Eleven patients with the diagnosis of pediatric trachyonychia were available for follow-up. The mean age of appearance was 2.7 years (range 2-7 yrs) and the average follow-up was 66 months (range 10-126 mos). Nine patients were treated with potent topical corticosteroids, one used only petrolatum, and one took vitamin supplements. One patient was found to have an additional skin and hair diagnosis of alopecia areata on follow-up. On follow-up, 82% noted improvement of the nails, whereas 18% noted no change. A majority of cases of pediatric trachyonychia are isolated and improve with time, regardless of treatment.

Outpatient use of oral propranolol and topical timolol for infantile hemangiomas: survey results and comparison with propranolol consensus statement guidelines.

Oral and topical ß-blockers are used to treat infantile hemangiomas (IHs). Although a recent consensus report provided guidelines for the treatment of IH with propranolol, there are no standard guidelines for the use of topical timolol. The objectives of this study were to determine the current use of oral propranolol and topical timolol by pediatric dermatologists in an outpatient setting and to compare current propranolol use with published propranolol consensus guidelines. An electronic survey was sent to pediatric dermatologists in May and June 2013. One hundred forty-nine pediatric dermatologists responded to the survey, a 79% response rate. Of the respondents, 96% prescribed oral propranolol, but 75% did not follow consensus guidelines exactly; recommended history, physical examination, initial dose, and frequency varied. The dose of propranolol was usually titrated up to goal dose as recommended (89%). Fifty-six percent monitored vital signs in patients after the initial dose and 49% continued to monitor vital signs in their clinic after each dose escalation, which did not meet consensus guideline recommendations. Ninety-one percent reported using topical timolol for the treatment of IH and 66% responded they had used topical timolol in conjunction with oral propranolol to treat IH. The most common indication was superficial hemangiomas (97%). Most practitioners (74%) did not routinely monitor heart rate or blood pressure in infants treated with topical timolol. This study highlights the variability in prescribing and monitoring practices of physicians using propranolol for the treatment of IHs and demonstrates that topical timolol is commonly used alone and in conjunction with oral propranolol to treat IHs.

Glomus tumors in individuals with neurofibromatosis type 1.

BACKGROUND: Glomus tumors have recently been reported in individuals with the neurofibromatosis type 1 (NF1) cancer disposition syndrome. We compare the clinical and molecular features of these painful hamartomas in a series of sporadic and NF1-associated cases. OBJECTIVE: We sought to evaluate the association of NF1 with glomus tumors and to compare NF1-associated glomus tumors with sporadic glomus tumors. METHODS: We conducted a retrospective cohort study of all individuals with a histopathologic diagnosis of glomus tumor at a large tertiary care center from January 1998 to January 2013. Charts were reviewed for a coexisting diagnosis of NF1. RESULTS: A total of 42 glomus tumors were identified in 34 individuals. Twelve (28.6%) were found in 6 patients with NF1. In 28 individuals with 30 sporadic tumors, there was no coexisting medical condition. Although multifocal tumors (16.7%) and tumor recurrence (33.3%) were more common in association with NF1, these trends did not reach statistical significance. NF1-associated glomus tumors exhibited no neurofibromin immunoreactivity, whereas their sporadic counterparts retained neurofibromin expression. LIMITATIONS: The retrospective design resulted in incomplete data capture. CONCLUSIONS: Detection of glomus tumors should raise suspicion for a concurrent diagnosis of NF1.

Oral glycopyrrolate for refractory pediatric and adolescent hyperhidrosis.

Primary hyperhidrosis is a common disorder affecting children and adolescents, and it can have a significant negative psychosocial effect. Treatment for pediatric hyperhidrosis tends to be limited by low efficacy, low adherence, and poor tolerance. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children. We present an institutional review of 12 children with severe, refractory hyperhidrosis treated with oral glycopyrrolate; 11 (92%) noted improvement and 9 (75%) would recommend oral glycopyrrolate to their friends. No significant side effects were noted. Our retrospective analysis suggests that oral glycopyrrolate is safe and effective in children with hyperhidrosis.