Atrichia with papular lesions in Syrian siblings exposing global diagnostic challenges in genetic alopecia: A rare case report

Congenital atrichia with papular lesions is a rare, recessively inherited condition of total alopecia, characterized clinically by complete and irreversible hair loss, which begins shortly after birth with the development of the papular lesions of keratin-filled cysts over an extensive area of the body. Mutations in the human hairless (HR) gene have been implicated in the pathogenesis of this disorder. To search for a mutation in human HR in a family with congenital atrichia. Linkage analysis was carried out using genotyping markers closely linked to congenital atrichia locus on chromosome 8p12. Subsequently, human HR was sequenced to identify a disease-causing mutation. A novel 11 bp insertion mutation, G202 (InsCTTCCCCCAGG), in exon 2 of the hairless gene was identified in a Pakistani consanguineous family affected by congenital atrichia. The insertion results in the expansion of 11 bp tandem repeat, which introduces a translational frameshift leading to downstream premature termination codon. This mutation is the first insertion mutation identified in the coding sequence of human HR. This extends our knowledge of mutations in HR that define the pathogenic basis of this disease.

Atrichia with papular lesions is a rare autosomal recessive condition characterized by complete irreversible hair loss during the first months of life and papules that appear during early childhood. Atrichia with papular lesions is frequently misdiagnosed as alopecia universalis, despite increasing reports of its prevalence and the presence of well-defined diagnostic criteria. Most cases of atrichia with papular lesions have been reported in consanguineous families residing in small geographical regions, but the increasing number of sporadic cases of unrelated individuals suggests that atrichia with papular lesions is more common than previously thought. Mutations in the human hairless gene on chromosome 8p12 have been implicated in this disease. Here, we report two novel heterozygous mutations in an Australian family and a novel homozygous mutation in 2 Arab siblings. We also revise the diagnostic criteria for atrichia with papular lesions in order to clarify its uniqueness and distinguishing features from alopecia universalis.

Heart failure (HF) is a global health burden and new strategies to achieve timely diagnosis and early intervention are urgently needed. Natriuretic peptide (NP) testing can be used to screen for left ventricular systolic dysfunction (LVSD), but evidence on test performance is mixed, and international HF guidelines differ in their recommendations. Our aim was to summarize the evidence on diagnostic accuracy of NP screening for LVSD in general and high-risk community populations and estimate optimal screening thresholds. We searched relevant databases up to August 2020 for studies with a screened community population of over 100 adults reporting NP performance to diagnose LVSD. Study inclusion, quality assessment, and data extraction were conducted independently and in duplicate. Diagnostic test meta-analysis used hierarchical summary receiver operating characteristic curves to obtain estimates of pooled accuracy to detect LVSD, with optimal thresholds obtained to maximize the sum of sensitivity and specificity. Twenty-four studies were identified, involving 26 565 participants: eight studies in high-risk populations (at least one cardiovascular risk factor), 12 studies in general populations, and four in both high-risk and general populations combined. For detecting LVSD in screened high-risk populations with N-terminal prohormone brain natriuretic peptide (NT-proBNP), the pooled sensitivity was 0.87 [95% confidence interval (CI) 0.73-0.94] and specificity 0.84 (95% CI 0.55-0.96); for BNP, sensitivity was 0.75 (95% CI 0.65-0.83) and specificity 0.78 (95% CI 0.72-0.84). Heterogeneity between studies was high with variations in positivity threshold. Due to a paucity of high-risk studies that assessed NP performance at multiple thresholds, it was not possible to calculate optimal thresholds for LVSD screening in high-risk populations alone. To provide an indication of where the positivity threshold might lie, the pooled accuracy for LVSD screening in high-risk and general community populations were combined and gave an optimal cut-off of 311pg/mL [sensitivity 0.74 (95% CI 0.53-0.88), specificity 0.85 (95% CI 0.68-0.93)] for NT-proBNP and 49pg/mL [sensitivity 0.68 (95% CI 0.45-0.85), specificity 0.81 (0.67-0.90)] for BNP. Our findings suggest that in high-risk community populations NP screening may accurately detect LVSD, potentially providing an important opportunity for diagnosis and early intervention. Our study highlights an urgent need for further prospective studies, as well as an individual participant data meta-analysis, to more precisely evaluate diagnostic accuracy and identify optimal screening thresholds in specifically defined community-based populations to inform future guideline recommendations.

Congenital alopecia has broad differential diagnosis and poses diagnostic and therapeutic challenges. It is a rare form of irreversible alopecia inherited autosomal recessively. Atrichia congenita with papular lesions represents a complex and heterogeneous group of genodermatoses characterized by irreversible complete hair loss soon after birth, and associated with the development of keratin-filled cysts over the body. We report a case of 4-year-old boy presenting with complete loss of hair over scalp, eye brows, eye lashes, and body since birth. Patient also had papular lesions over body.

Evaluation of hair loss

Atrichia with papular lesions (APL) is a hair abnormality characterized by loss of hair on the scalp and rest of the body. In a few cases, hair loss is accompanied by the appearance of keratotic papules on the body. It is inherited in an autosomal recessive manner. Sequence variants in the HR (hairless) gene are responsible for this hair abnormality. Here, we present nine consanguineous families and one nonconsanguineous family with clinical manifestations of APL. Whole exome followed by Sanger sequencing and/or direct Sanger sequencing was performed to identify pathogenic variants. The study revealed seven novel pathogenic variants c.794del;p.(Pro265Argfs*98), c.2921-2936del;p.(Tyr974Leufs*16), c.2889C>A;p.(Cys963*), c.2689C>T;p.(Gln897*), c.3186_3187dup;p.(Gln1063Profs*43), c.560dup;p.(Tyr188Ilefs*131), c.2203+5G>C, c.2776+5G>A, and the previously reported variant c.1837C>T;p.(Arg613*) in HR in these families. The study not only expands the mutational spectrum in the HR gene but also highlights the unusual phenotypic findings and will facilitate genetic counseling of families with members showing various types of hair loss disorders in the local population.

Clinicopathologic findings of guttate leukoderma in Darier disease: A helpful diagnostic feature

<p>Congenital atrichia or papular atrichia is a rare form of irreversible alopecia inherited autosomal recessively. Atrichia congenita with papular lesions represents a complex and heterogeneous group of genodermatoses characterized by irreversible complete hair loss soon after birth, and associated with the development of keratin-filled cysts over the body. Mutation of the human hairless (HR) gene on chromosome 8p22 has been implicated with this condition. It has broad differential diagnosis and poses diagnostic and therapeutic challenges. We report an 8 year girl presenting with complete loss of hair over scalp, eye brows, eye lashes, and body soon after birth with papular lesions over face.<strong></strong></p>

Introduction Patients with breast cancer who received chemotherapy have distressing side effects such as mucositis, alopecia, gastritis, and BM suppression. Chemotherapy-induced alopecia(CIA) is one of considerable psychological events in self-esteem in patients with breast cancer, but the possibility of irreversible alopecia is often overlooked by physician. We investigated clinical characteristics of CIA and prevalence of irreversible severe hair loss in patient with breast cancer who received chemotherapy. Methods We conducted a survey to collect demographic information about CIA with 150 breast cancer patients who had passed at least 6 months since their last day of chemotherapy from February 2015 to May 2015 in Yonsei Cancer Center. We obtained clinical information as age, elapsed time from end of chemotherapy, chemotherapy regimen, and other adjuvant therapy using their electrical medical records. We compared irreversible CIA characters between anthracycline and cyclophosphamide (AC) and taxane based regimen groups. The severe alopecia was defined as the hair density loss over 50% compared to the hair density before chemotherapy. Results The mean age at chemotherapy was 48 years old (±17.3) and the mean elapsed time after chemotherapy was 37 months (±9.5) in total patients. Remnant alopecia was reported in 71 patients (47.3%). Wig or hat were used in 39 patients (26.0%). The mean satisfaction score with a five-point scale was 4 in patients without alopecia or hair character change and 2.2 in patients with irreversible alopecia (p<0.001). The severe irreversible hair loss was complained by the 12 (8.2%) patients. AC and taxane based chemotherapy were carried out in 65 and 85 patients, respectively. In AC group, remnant alopecia was shown in 18 patients (27.7%), and more than a half of patients in taxane group, 53 patients (62.4%), showed remnant alopecia (p<0.001). While only five patients (7.8%) in AC group suffered for severe hair loss, 26 patients (31.3%) in taxane group were affected by severe hair loss (p=0.001). The mean satisfaction level of hair status in patients in taxane group was 2.5 as compared to 3.6 in those in AC group (p<0.001). Conclusion Contrary to general expectation, About a half of breast cancer patients who received chemotherapy complained of irreversible hair loss even though at least 6 months has elapsed since the end of chemotherpy. In particular, patients with taxane based chemotherapy had more irreversible and severe alopecia than those with AC chemotherapy. Citation Format: Kim S, Park HS, Kim JY, Nam S, Kim GM, Sohn JH, Kim SI. Irriversible chemotherapy-induced alopecia in breast cancer patient. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-15-04.

Atrichia with papular lesions (APL) is a rare autosomal recessive disorder resulting in complete and irreversible hair loss shortly after birth. Affected individuals also develop papular lesions of keratin-filled follicular cysts over extensive areas of the body. Mutations in the hairless gene, a putative single zinc-finger transcription factor protein, have been implicated in the pathogenesis of APL. In this report, we describe a novel missense mutation, E583V, in the hairless gene in an Italian family affected with APL. The mutation resides between the LXXLL motif found in TRIPs (thyroid hormone receptor interacting proteins) in exon 5 and the six-cysteine zinc-finger motif in exon 6. The amino acid sequence neighbouring the LXXLL motif and zinc-finger domain is highly conserved in human, monkey, rat, and mouse hairless proteins. Our finding extends the body of evidence that supports the importance of the zinc-finger and LXXLL domains in the function of the hairless protein. Moreover, we continue to find small APL families without consanguinity from around the world.

Atrichia with papular lesions (APL) is a rare autosomal recessive form of total alopecia, characterized by hair loss soon after birth and the development of papular lesions of keratin-filled cysts over extensive areas of the body. Mutations in the hairless (hr) gene, a putative single zinc finger transcription factor, have been implicated in the pathogenesis of this disorder. In the present study, we describe two novel deletion mutations in exons 2 and 8 of the human hairless gene leading to frameshift and downstream premature termination codons in two consanguineous Pakistani families affected with atrichia.

Benefits and harms of screening for hepatocellular carcinoma in high-risk populations: systematic review and meta-analysis

Efficacy of tofacitinib in treatment of alopecia universalis in two patients

Atrichia with papular lesions (APL) is a rare irreversible form of complete hair loss inherited in autosomal recessive manner. Hair loss is often followed by the appearance of multiple keratin-filled cysts or papules on exterior parts of the body. This phenotype results due to mutations in the human hairless gene (HR) mapped on chromosome 8p21.3. The present study was aimed to search for disease-causing sequence variants in the HR gene in five consanguineous families exhibiting features of APL. Linkage in five Pakistani lineal consanguineous families, displaying features of APL, was tested using microsatellite markers flanking the HR gene on chromosome 8p21.3. After constructing the haplotypes, variants in the gene HR were searched by dideoxy-chain termination sequencing. Haplotype analysis established linkage in all five families to the HR gene located on chromosome 8p.21.3. Subsequently, sequencing HR identified a novel homozygous nonsense variant (c.2541G>A, p.Trp847*) in one and previously reported two pathogenic variants (p.Cys690*, p.Pro1157Arg) in the other four families. Mutations identified extend the spectrum of mutations in the HR gene resulting in APL. Characterizing the clinical spectrum resulting from the disease-causing homozygous variants in the HR gene will direct clinical care of the family members.

A Summary of the 2020 Gastric Cancer Summit at Stanford University