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.

Atypical pediatric presentation of alopecic and aseptic nodules of the scalp with features of dissecting cellulitis.

Alopecic and aseptic nodules of the scalp (AANS) and dissecting cellulitis of the scalp (DCS) are rare, closely related conditions of young men that exclusively affect the hair-bearing scalp. We describe a 9-year-old boy who presented with a 6-year history of chronically relapsing, sterile, partially scarring nodules of the scalp and facial skin. Histopathology revealed mixed inflammatory infiltrates consisting of neutrophils, macrophages, lymphocytes, and plasma cells in the deep dermis, consistent with the morphological pattern of suppurative, partly granulomatous dermatitis. The present atypical case is characterized by prepubertal onset and facial involvement which, to our knowledge, has not yet been described before, may be included in the spectrum of "typical" AANS and "typical" DCS.

Erosive Pustular Dermatosis of the Scalp.

Erosive pustular dermatosis (EPD) is a rare entity, but it is generally overlooked or missed, rather than rarely encountered. It presents with erosions and shallow ulcers, accompanied by delayed healing and associated with cutaneous atrophy, rather than pustules. It exhibits predominance for women, with a predilection for a chronically sun-damaged scalp and, less commonly, the extremities, particularly the legs, as well as the face and mucosal surfaces. The role of infection, actinic damage, trauma, hormones, autoimmune disease, cutaneous atrophy, and genetics in the pathogenesis of EPD has been described in literature. Increased awareness and a high index of suspicion permit prompt treatment with topical corticosteroids, with or without oral zinc, followed by maintenance therapy with topical calcineurin inhibitors. Prevention, prior recognition, and prompt treatment are required for addressing this complex condition. (SKINmed. 2023;21:12-19).

Clinical benefit and tolerance profile of a keratolytic and hydrating shampoo in subjects with mild to moderate psoriasis. Results from a double-blind, randomized, vehicle-controlled study.

INTRODUCTION: Scalp psoriasis frequently goes with other disease location and may lead to a significant burden and impairment of quality of life (QoL). Adherence to local treatments is a frequent problem. A keratolytic and hydrating shampoo containing 2% salicylic acid, 5% urea, and 1% glycerin (active shampoo) has been developed for psoriasis-prone scalp. OBJECTIVE: To assess the efficacy and tolerability of an active shampoo in subjects with mild to moderate scalp psoriasis. MATERIALS AND METHODS: A single-center, randomized, double-blind, vehicle-controlled study was conducted on 67 adults with mild to moderate psoriasis. The active shampoo or its vehicle were applied daily for 14 days and 3 times/week for another 14 days. Assessments included the Psoriasis Scalp Severity Index (PSSI), Investigator Global Assessment (IGA), calculated total surface affected hair, scalp greasiness, irritation, and assessed scalp dermatitis-specific quality-of-life issues using SCALPDEX and product acceptability. RESULTS: The active shampoo significantly (p < 0.05) reduced the PSSI by 39.0%, 37.2%, 63.0%, and 69.0% immediately after washing compared to a 22.8%, 5.5%, 19.6%, and 13.0% with the vehicle at Days 1, 8, 15, and 30, respectively. SCALPDEX items, IGA, and irritation significantly (p < 0.05) reduced with the active shampoo. Hair and scalp greasiness improved continuously with both products until Day 21. Subject-reported symptom scores paralleled the positive evolution of clinical signs. The active shampoo was well tolerated, subjects were highly satisfied and had an improved QoL. CONCLUSION: The active shampoo significantly improved clinical signs, symptoms, and QoL of mild-to-moderate scalp psoriasis compared to the vehicle. It was very well tolerated and highly appreciated by the subjects.

Cuero cabelludo sensible: diagnóstico y manejo práctico / Sensitive Scalp: Diagnosis and Practical Management

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

[Translated article] Sensitive Scalp: Diagnosis and Practical Management / Cuero cabelludo sensible: diagnóstico y manejo práctico

Sensitive scalp is sensitive skin located on the scalp. Sensitivity is considered primary in the absence of an associated scalp disorder and secondary when caused by conditions such as psoriasis, seborrheic dermatitis, and atopic dermatitis. The clinical manifestations of primary sensitive scalp are subjective. Common presenting symptoms are burning, itching, trichodynia, and dysesthesia, often coinciding with hair loss. Clinically, the skin appears normal or red. An objective diagnosis based on laboratory or histologic findings is not possible. Triggers may be endogenous (e.g., stress and emotional or psychopathological disturbances) or exogeneous (e.g., topical products and cosmetics). Treatment must be individualized. Options include pimecrolimus, hydration with hyaluronic acid, and mesotherapy with plasma rich in growth factors (AU)

El cuero cabelludo sensible es una piel sensible de localización especial. Puede ser primario, cuando se presenta sin enfermedad del cuero cabelludo, y secundario cuando es atribuible a procesos como psoriasis, dermatitis seborreica, dermatitis atópica y otros. Las manifestaciones clínicas de la forma primaria son subjetivas. El escozor, picor, tricodinia y sensaciones disestésicas son el motivo de consulta, muy a menudo coincidiendo con alopecia. Clínicamente la piel del cuero cabelludo puede ser normal o eritematosa. No hay datos de laboratorio o histológicos específicos para un diagnóstico objetivo. Los factores desencadenantes son endógenos como el estrés y alteraciones emocionales y psicopatológicas, o ambientales como los tópicos inadecuados y los cosméticos. El tratamiento debe ser personalizado, incluyendo pimecrólimus, la hidratación con ácido hialurónico, y la mesoterapia con plasma rico en factores de crecimiento (AU)

Trichoscopy beyond scalp. A narrative review.

Dermoscopy is becoming an indispensable tool in everyday practice, with an expanding range of applications. Trichoscopy is effective not only in establishing the diagnosis of scalp disorders but also in the follow-up of treatment. The MEDLINE database was searched using the terms "dermoscopy" and "trichoscopy" in combination with each of the following: "axilla," "pubic area," "beard," "eyebrows," "eyelashes," and "body hairs." We included case reports, case series, and review articles mentioning the previous terms. By providing an updated review from the literature, we aimed to emphasize the potential uses of trichoscopy in detecting diseases in hairy locations other than the scalp. Various inflammatory conditions, infections, and infestations are discussed.

Cutaneous squamous cell carcinoma in an autosomal-recessive Adams-Oliver syndrome patient with a novel frameshift pathogenic variant in the EOGT gene.

Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.