Association of Central Precocious Puberty with a Rare Presentation of Schimmelpenning–Feuerstein–Mims Syndrome in a Peruvian Girl

Abstract

<jats:p>Schimmelpenning–Feuerstein–Mims syndrome (SFM), an epidermal nevus syndrome characterized by skin lesions, has an estimated incidence of 1 per 10 000 live births. Nevus sebaceous, the most common cutaneous lesion, and verrucous nevus, the less frequent lesion, are coupled with a wide range of extracutaneous manifestations. As part of these manifestations, rarely, central precocious puberty can arise. We report the case of a 1-year-5-month-old girl who presented to the Endocrinology and Metabolism Department with breast enlargement that began at one year of age, growth of pubic and axillary hair three months later, and vaginal bleeding that occurred five months later. During clinical examination, melanocytic nevi, with a diameter ranging from 3 to 5 mm, were noted on the face. Verrucous nevi of variable size with a tendency for coalescence following the lines of Blaschko and melanocytic nevi with a diameter ranging from 3 to 6 mm were observed on the right hemibody and on the left hemibody, respectively. Right asymmetry of the lower extremities was observed. Laboratory findings showed a significant increase in the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after the gonadotropin-releasing hormone (GnRH) stimulation test; additionally, imaging demonstrated advanced bone age and pubertal changes in the internal genitals. Analyses of the H-RAS, K-RAS, and N-RAS genes in the blood and in the skin were performed, and a missense mutation in exon 2 of the gene, H-RAS c37G &gt; C (p.G13R), was detected in the latter. Treatment with triptorelin, a GnRH analog, was initiated, and it gave good clinical response. Epidermal nevus syndrome has a wide and variable systemic involvement. Thus, it is important to consider the development of precocious puberty for a prompt diagnosis and to strategize a multidisciplinary approach from the beginning.</jats:p>

Nevus Sebaceous Syndrome: A Case Report and Literature Review of the Associated Neurological Complications

“…Developmental Delays: De Vito et al [60], Israni et al [36], Ullah et al [37]. "Other" includes nystagmus, right-sided weakness, headaches [35], significant scoliosis, and musculoskeletal pains [38]. The patient with scoliosis and musculoskeletal pains was also diagnosed with hypophosphatemia.…”

“…Importantly, the earlier in embryogenesis they occur, the more widespread the nevus and the greater the chance (and more extensive and severe) of extracutaneous anomalies. Among patients diagnosed with NSS (which we consider identical to LNSS), HRAS mutations were the most common, including G13R [34,35,[48][49][50][51], G12C [25], G12S [26], and G13V [23], as were KRAS mutations, specifically G12D [14,22,24,25,26,27,30], G12V [28], G12C [20,53], and A146T [31]. One NRAS mutation (Q61R) was found, marking the first causative NRAS mutation in NSS [5], as well as unique mutations such as in the PRKRIR gene (A1674T, R558S) for one patient, and a mutation in the RRP7A gene (C670T, R224W) in another [27].…”

Sebaceous nevus of Jadassohn: review and clinical-surgical approach

“…6,15 Studies have indicated the presence of androgen receptors in nevus sebaceous, 4 so that lesions take on a verrucous appearance and a more intense color, due to the processes of hyperkeratosis, papillomatosis, and acanthosis. 6,14,15 Finally, the third stage is seen in the adulthood, when there is a higher risk of secondary neoplasm development. 6,15 A linear nevus is usually reported in Schimmelpenning-Feuerstein-Mims syndrome and, as a component of multisystemic disorders, which have been previously described in a wide variety of organs, such as the nervous, ocular, cardiovascular, muscular, urogenital systems, and bones, among others.…”

“…6,15 A linear nevus is usually reported in Schimmelpenning-Feuerstein-Mims syndrome and, as a component of multisystemic disorders, which have been previously described in a wide variety of organs, such as the nervous, ocular, cardiovascular, muscular, urogenital systems, and bones, among others. 14,15,22,23 Aiming to facilitate the identification and clinical diagnosis, Table 1 shows the main disorders that have been previously identified and related to Schimmelpenning-Feuerstein-Mims syndrome, among which the most frequently reported in the literature are: hypophosphatemic rickets, intellectual disability, and cognitive impairment, coloboma and strabismus. 5,11,22…”

Identification of a recurrent mosaic KRAS variant in brain tissue from an individual with nevus sebaceous syndrome

“…Conversely, in the rarer individuals with NSS, KRAS appears to be more common in 13 reported individuals in whom the molecular basis has been determined with the identification of postzygotic variants. Of those 13 reported individuals with NSS, KRAS variants account for nine, with HRAS variants in three and NRAS in one ( Groesser et al 2012 ; Sun et al 2013 ; Kuroda et al 2015 ; Igawa et al 2016 ; Jiang et al 2017 ; Mitchell et al 2018 ; Chacon-Camacho et al 2019 ; Nagatsuma et al 2019 ; De los Santos-La Torre et al 2020 ; Pan et al 2020 ; Pepi et al 2021 ). Pathogenic variants tend to be recurrent affecting residues functionally conserved across all RAS proteins ( Groesser et al 2012 ).…”