Characterization of a New Variant in ARHGAP31 Probably Involved in Adams-Oliver Syndrome in a Family with a Variable Phenotypic Spectrum.

Adams-Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams-Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams-Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence.

Efficacy and safety of tralokinumab in the treatment of head and neck pattern atopic dermatitis: A multicentre study of 12 patients.

BACKGROUND/OBJECTIVES: The evaluation of the efficacy and safety of new molecules for atopic dermatitis (AD) in real clinical practice is very important to obtain information that clinical trials (EECC) lack. The pattern of AD in the head and neck (H&N) continues to be a challenge in treatment today, despite the new molecules, and real-life data on the use of tralokinumab is still missing. This is the first daily practice study of tralokinumab treatment in patients with H&N AD pattern. The objective is to evaluate the efficacy and safety of tralokinumab in the short term (16 weeks) in patients with AD with H&N pattern, for the first time. METHODS: A multicentre prospective observational study was conducted, including patients with moderate-severe AD and H&N pattern who started tralokinumab treatment in four hospitals in Andalusia. Values of severity and quality of life scales, as well as patient-reported outcomes (PROs), were collected at baseline and at Weeks 4 and 16. Safety events were also recorded. RESULTS: Twelve patients were included. An improvement was observed in all efficacy and quality of life parameters evaluated at 16 weeks with respect to the baseline. No serious adverse events were recorded. CONCLUSIONS: In real clinical practice, tralokinumab is demonstrated to be an effective and safe treatment for patients with AD and H&N pattern at short term.

Photodynamic therapy combined with carbon dioxide laser pretreatment for treatment of perifolliculitis capitis abscedens et suffodiens: A case report.

Perifolliculitis capitis abscedens et suffodiens (PCAS) is a refractory and recrudescent chronic inflammatory dermatosis of the scalp, which seriously affects the appearance and quality of life of patients. The treatment of PCAS is challenging, often leading to frustrating outcome. In this paper, we report a case of PCAS who received 20 % 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with carbon dioxide (CO2) laser pretreatment. The skin lesions of this case showed complete clearance after 2 month, and there was no recurrence after 1 year of follow-up. To our knowledge, we presented the first successful regimen of ALA-PDT combined with CO2 laser therapy for PCAS.

FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

Cutis verticis gyrata associated with congenital heart disease.

Cutis verticis gyrata (CVG) is a very rare benign disorder characterised by convoluted folds and deep furrows of the scalp that mimic cerebral sulci and gyri. Associations with other pathologies as neuropsychiatric and/or ophthalmologic disorders, secondary cases to inflammatory or neoplastic processes, as well as cases associated to genetic disorders as Turner's syndrome have been reported, but there is no literature describing an association with a congenital structural heart defect and no other underlying condition. We report a case of primary CVG in a 3-week-old female infant associated with an echocardiographic diagnosis of cor triatriatum. Other systemic examination findings and investigations were unremarkable, and the patient has normal neurodevelopment at 1 year old. Aside from the neuropsychiatric and ophthalmologic pathologies commonly associated with primary non-essential CVG, it should be noted that isolated congenital cardiac lesions are also possible, so as to increase our index of suspicion in patients with the disorder.

Pediculicide regulations and usage trends in Türkiye in 2015-2022.

BACKGROUND: Over the years, the increasing prevalence of head lice infestation has led to an increase in treatment-related costs and the development of resistance to pediculicides. This study aimed to evaluate pediculicide sales over an 8-year period (2015-2022), including the COVID-19 pandemic. METHODS: Data on products registered in the Turkish Pharmaceutical Index Dataview, Intercontinental Medical Statistics (IMS) database, sold on prescription and approved by the Ministry of Health in Türkiye were formally requested from the research organization IQVIA for pharmacologically active pediculicides (PAP) such as permethrin, pyrethrin, and sumithrin. Data for physically active products containing dimethicone (DMT) were obtained from the relevant pharmaceutical companies. Sale revenues were determined based on sale prices in the aforementioned year. RESULTS: Total sales of pediculicides decreased from 2,452,846 units in 2015 to 2,028,840 units in 2022. While PAP consumption decreased over the years, from 1,832,006 to 518,460 units, DMT consumption increased from 620,840 to 1,510,380 units, from 2015 to 2022. The total price of pediculicides for the consumer increased more than threefold in Turkish currency. In terms of USD, an almost similar amount of money was spent over the years, with the exception of 2022 when the expenditure almost halved mainly due to the high inflation rate in the country. CONCLUSION: The decrease in PAP and the increase in DMT indicate that local lice have developed resistance to the former. Further studies are needed to determine the possible development of resistance in the country.

Localized Congenital Cutis Verticis Gyrate with Skull Erosion.

Localized congenital cutis verticis gyrate (CVG) is rare and potentially risks skull involvement. A 23-year-old woman presented with a congenital scalp mass in the occipital region. Local thickening of her left occipital scalp with ridges and furrows was observed on examination. Head computed tomography scan showed a lytic area underneath the same area of the occipital calvarium. The mass was surgically removed due to the skull erosion and cosmetic reasons. Pathologic evaluation established CVG. Surgical excision is best for localized congenital CVG with skull erosion due to cosmetic reasons. Surgical excision was rewarding to the patient it allowed her to style her hair.

Ultrasound Pattern of Cutis Verticis Gyrata.

Cutis verticis gyrata (CVG) is a cutaneous benign condition that usually presents symmetric or asymmetric convoluted folds and deep furrows in the scalp, which mimic the disposition of the cerebral sulci and gyri. This scalp deformation may be a worrying situation for the patients and their families. Clinically, its diagnosis may be challenging because it can mimic other cutaneous conditions. So far, the ultrasonographic pattern of CVG has not been reported. Thus, we aim to review the ultrasound findings of this entity. All patients (n = 14) presented zones with dermal and hypodermal thickening that corresponded with the elevated clinical zones, followed by folds with normal cutaneous thicknesses. There was undulation of the cutaneous layers in all cases. The scalp areas involved the frontal, parietal, and occipital regions bilaterally. The mean maximum dermal and hypodermal thicknesses and echogenicities and the color Doppler characteristics are provided. No significant dilation of the hair follicles was detected. In conclusion, CVG presents an ultrasonographic pattern that can support its diagnosis and follow-up. This can help its differential diagnosis with other scalp dermatologic conditions.