Inflammatory linear verrucous epidermal nevus in groin and labia with claudication: Successfully treated with photodynamic therapy.

SIGNIFICANCE: Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon type of epidermal nevus and is refractory to therapy. We report the effectiveness of photodynamic therapy (PDT) for treating ILVEN with claudication in a young girl. ADDITIONAL CONTRIBUTIONS: We thank the patient for granting permission to publish this information. APPROACH: Aminolaevulinic Acid Hydrochloride (ALA) photodynamic therapy (PDT) was applied six times in 1-month interval. RESULTS: Most lesions and pruritus have subsided markedly, with mild scarring and a marked reduction in claudication. CONCLUSIONS: ALA PDT might be an effective and promising treatment for ILVEN in the future.

Expansion of the complex genotypic and phenotypic spectrum of FGFR2-associated neurocutaneous syndromes.

The fibroblast growth factor receptors comprise a family of related but individually distinct tyrosine kinase receptors. Within this family, FGFR2 is a key regulator in many biological processes, e.g., cell proliferation, tumorigenesis, metastasis, and angiogenesis. Heterozygous activating non-mosaic germline variants in FGFR2 have been linked to numerous autosomal dominantly inherited disorders including several craniosynostoses and skeletal dysplasia syndromes. We report on a girl with cutaneous nevi, ocular malformations, macrocephaly, mild developmental delay, and the initial clinical diagnosis of Schimmelpenning-Feuerstein-Mims syndrome, a very rare mosaic neurocutaneous disorder caused by postzygotic missense variants in HRAS, KRAS, and NRAS. Exome sequencing of blood and affected skin tissue identified the mosaic variant c.1647=/T > G p.(Asn549=/Lys) in FGFR2, upstream of the RAS signaling pathway. The variant is located in the tyrosine kinase domain of FGFR2 in a region that regulates the activity of the receptor and structural mapping and functional characterization revealed that it results in constitutive receptor activation. Overall, our findings indicate FGFR2-associated neurocutaneous syndrome as the accurate clinical-molecular diagnosis for the reported individual, and thereby expand the complex genotypic and phenotypic spectrum of FGFR-associated disorders. We conclude that molecular analysis of FGFR2 should be considered in the genetic workup of individuals with the clinical suspicion of a mosaic neurocutaneous condition, as the knowledge of the molecular cause might have relevant implications for genetic counseling, prognosis, tumor surveillance and potential treatment options.

Schimmelpenning-Feuerstein-Mims syndrome with benign enlargement of subarachnoid space in infancy.

Schimmelpenning-Feuerstein-Mims syndrome is a rare disorder generally characterised by a craniofacial nevus with multisystemic presentations. Our patient, an infant, was brought to the emergency department in a postictal state following a first seizure episode. A physical examination showed a solitary dark brown, well-demarcated verrucous plaque extending from the patient's left temporal region to the left mandible without crossing the midline. Epibulbar choristomas were present on the ipsilateral side of the craniofacial lesion. Neuroimaging showed benign enlargement of the subarachnoid space. Due to the known risk of seizures associated with this condition, the patient was started on levetiracetam and showed adequate compliance. We present this as the first reported case of Schimmelpenning-Feuerstein-Mims syndrome with benign enlargement of the subarachnoid space in an infant presenting with seizures to emphasise the value of collaboration among multidisciplinary professionals to improve the quality of care for such patients.

Nevo sebáceo de Jadassohn. Localización atípica y síndromes asociados / Nevus sebaceus of Jadassohn. Atypical location and associated syndromes

Hamartoma benigno que puede aparecer desde el nacimiento. Se localiza sobre todo en cuero cabelludo y cara; origina una placa alopécica, amarillenta, de superficie rugosa. Tiene tres etapas, una de hiperplasia epidérmica, luego una puberal con desarrollo de glándulas sebáceas y una tardía con desarrollo de tumores benignos o malignos, en especial siringocistadenoma papilífero y tricoblastomas. Puede presentarse asociado a síndromes genéticos. Su exéresis quirúrgica es objeto de controversia (AU)

Benign hamartoma that can appear from birth. It is located mainly on the scalp and face; It causes an alopecic, yellowish plaque with a rough surface. It has three stages, one of epidermal hyperplasia, then a pubertal stage with development of sebaceous glands, and a late stage with development of benign or malignant tumors, especially papillary syringocystadenoma and trichoblastoma. It can appear associated with genetic syndromes. Its surgical excision is controversial. (AU)

Schimmelpenning-Feuerstein-Mims syndrome induced by HRAS Gly12Ser somatic mosaic mutation: Case report and literature review.

Schimmelpenning-Feuerstein-Mims syndrome (SFMS), an epidermal nevus disease, features skin lesions including craniofacial nevus sebaceous and extracutaneous anomalies (e.g. brain, eye, and bone). Recent genetic studies implicate HRAS, KRAS, and NRAS genes in somatic mutations. Our case, a 48-year-old man, presented with nevus sebaceous on the scalp; pigmented skin lesions on the right side of his neck, back, and chest along the Blaschko lines; a history of epilepsy; and mild intellectual disability. Accordingly, SFMS was suspected. DNA analysis of nevus sebaceous skin and peripheral blood leukocytes showed a pathogenic HRAS variant NM_005343.4:c.34G > A p.(Gly12Ser) in biopsy specimens from different skin layers but not blood, indicating somatic mosaic mutation. Until now, the HRAS p.(Gly12Ser) mutation has been reported in somatic RASopathies but not SFMS. The authors report this mutation in a case of SFMS, review another 15 cases of SFMS, and discuss HRAS c.34G > A p.(Gly12Ser) somatic mutations. RAS mutations of somatic RASopathies share activating hotspot mutations found in cancers, and produce different phenotypes depending on the developmental stage at which the somatic mutations occur.

A case of successful treatment of concurrent verrucous epidermal naevi and psoriasis with apremilast.

In a rare case of concurrent verrucous epidermal naevi (VEN) with psoriasis, previous treatments with oral methotrexate and acitretin showed minimal improvement. However, treatment with oral apremilast resulted in complete resolution of psoriasis and significant improvement in VEN lesions after 1 month. This is the first documented case of successful VEN treatment with apremilast, highlighting its potential efficacy in treating verrucous epidermal naevus. Further studies are needed to validate its effectiveness.

Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway.

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction of KRASG12V in the developing mouse cortex results in subcortical nodular heterotopia and enhanced excitability, recapitulating major pathological manifestations of LNSS. Moreover, we show that decreased firing frequency of inhibitory neurons without KRASG12V expression leads to disrupted excitation and inhibition balance. Transcriptional profiling after destabilization domain-mediated clearance of KRASG12V in human neural progenitors and differentiating neurons identifies reversible functional networks underlying LNSS. Neurons expressing KRASG12V show molecular changes associated with delayed neuronal maturation, most of which are restored by KRASG12V clearance. These findings provide insights into the molecular networks underlying the reversibility of some of the neuropathologies observed in LNSS caused by dysregulation of the RAS pathway.

Verrucous epidermal nevus as a manifestation of a type 2 mosaic PTEN mutation in Cowden syndrome.

Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature.

Report of a case of RAVEN, hair heterochromia and autism in the setting of FGFR2 mutation.

A newborn presented with extensive rounded and velvety epidermal nevus (RAVEN) with a genetic study of the cutaneous lesions revealing a heterozygous mutation in FGFR2 (p.Cys382Arg). By 2 years of age, the patient developed hair heterochromia and autism spectrum disorder. Although RAVEN was initially associated with fibroblast growth factor 3 (FGFR3) mutations, three cases of RAVEN have been identified with mutations in FGFR2 (p.Ser252Trp) and one case of linear keratinocytic epidermal nevi has been identified with the same mutation as the mutation identified in our patient. This strongly supports the pathogenic role of these mutations.

Basal cell carcinoma arising on two variants of epidermal nevus: A case series

Introduction@#Epidermal nevi are hamartomas of the epidermis and papillary dermis that are usually present during the first years of life. Rarely, malignant transformations develop in association with epidermal nevi. Few cases have been reported worldwide, however the lifetime risk and incidence are unknown. @*Case Report@#This is a case series about basal cell carcinoma arising on epidermal nevus. The first patient is a 42-year-old Filipino female, who presented with a verrucous plaque at birth on the left temple which then developed multiple, discrete to confluent, grayish, papules and nodules on the surface. Histological examination revealed nevus sebaceus and basal cell carcinoma, pigmented type. The second patient is a 53-year-old Filipino male, who presented with a papillomatous plaque on the left temple since the first year of life which then increased in size along with the presence of a solitary bluish-black macule noted by dermoscopic examination. Histologic examination showed verrucous epidermal nevus and basal cell carcinoma, pigmented type.@*Conclusion@#Two rare cases of basal cell carcinoma arising on epidermal nevus are reported. Despite the rarity of malignant transformation on epidermal nevus, any suspicious growth warrants a biopsy. Knowledge of these cases is important for probing suspicious growth over an epidermal nevus that would prompt early treatment before these lesions progress in size making it harder to manage.

Sebaceous nevus of Jadassohn: review and clinical-surgical approach.

BACKGROUND: Nevus sebaceous of Jadassohn is defined as a rare congenital malformation characterized as a non-hereditary hamartoma of the adnexal structures of the skin. Its etiology is not yet well understood, but it is believed to be related to post-zygotic mutations in the HRAS, NRAS and KRAS genes. OBJECTIVE: To describe the clinical manifestation of nevus sebaceous, as well as the main management techniques addressed in the medical literature. Moreover, the present study discusses a case report of a congenital linear nevus in the left retroauricular region found in a male patient, without extracutaneous manifestations. METHOD: A narrative review of the literature was carried out. DISCUSSION: Nevus sebaceous occurs as lesions with a linear or oval appearance, with a smooth or verrucous texture, generally alopecic and with very variable color. Moreover, nevus sebaceous is one of the components of the so-called linear nevus syndrome or Schimmelpenning-Feuerstein-Mims syndrome, which is associated with multisystemic complications. The treatment of the lesions is still controversial; however, most experts indicate surgical excision as the most frequently adopted treatment method, in addition to multidisciplinary follow-up when the diagnosis of Schimmelpenning-Feuerstein-Mims syndrome is established. CONCLUSION: The linear nevus syndrome constitutes a rare manifestation; however, its diagnosis should be considered in children born with nevus sebaceous. There is no consensus yet on the best therapy, but surgical removal has shown to be a viable option.