Noonan syndrome-like disorder: Case report and review of the literature.

Of patients with a Noonan syndrome phenotype, only about 1% are found to be related to pathological variants in CBL, also known as Noonan syndrome-like disorder (NSLD). We present a case of a 4-year-old boy diagnosed with NSLD, presenting with multiple melanocytic nevi and superficial neurofibromas. A literature review identified common cutaneous findings of NSLD, for example, café-au-lait macules (22%), juvenile xanthogranuloma (16%), and thin hair (10%). As there are no documented cases of neurofibromas associated with NSLD, and only a single report of multiple melanocytic nevi, inclusion of these features in the phenotype may be warranted and mitigate the necessity for future biopsies in other children.

Phacomatosis pigmentokeratotica: Exploring extracutaneous comorbidities and topical therapy.

Phacomatosis pigmentokeratotica (PPK) is a RASopathy characterized by the presence of a sebaceous nevus and a papular speckled lentiginous nevus. This case report highlights the associated extracutaneous comorbidities, including life-threatening arrhythmia, and introduces topical rapamycin as a potential therapeutic avenue for sebaceous nevus in PPK patients.

Dermatology Life Quality Index survey in patients with Down syndrome and caregivers.

Down syndrome (DS) is associated with many dermatological conditions, including hidradenitis suppurativa, folliculitis, and alopecia areata. Despite the high incidence of skin conditions in this population, there are no quality of life (QoL) studies in the dermatology literature focused on patients with DS or their caregivers. The frequently used QoL assessment tool, the Dermatology Life Quality Index (DLQI), has yet to be studied in this population. This study addresses these disparities by capturing how various skin conditions affect the QoL of people with DS and their caregivers and assessing the utility of the DLQI.

Widespread keratinocytic epidermal nevus with an associated chylous pericardial effusion.

A 17-year-old male presented for review of a widespread keratinocytic epidermal nevus (KEN) in the setting of a chronic pericardial effusion. Biopsy of the epidermal nevus revealed a KRAS mutation. Pericardiocentesis revealed a chylous effusion and magnetic resonance lymphangiogram demonstrated an underlying lymphatic malformation. There are rare case reports of KEN with an associated KRAS mutation. This case highlights the importance of being alert to epidermal nevus syndrome, particularly in patients with a widespread nevus and seemingly unrelated pathology.

Oral candidiasis and seborrheic dermatitis in an 8-year-old female with a heterozygous variant of the IL-17RC gene.

An 8-year-old female with chronic oral candidiasis and severe seborrheic dermatitis was found to have a heterozygous mutation (p.R14X c.40 C>T) of the IL-17RC gene, which was predicted to possibly represent a new pathogenic variant via truncation or nonsense-mediated mRNA decay. Given previously reported IL-17RC-related disorders are autosomal recessive, we would expect an affected individual to have two mutated alleles whereas our patient was heterozygous. Given the overlapping clinical picture, this variant could be responsible for altered immunity against both Candida and Malassezia species. This is the first report to our knowledge of chronic oral candidiasis and severe seborrheic dermatitis in a patient with a heterozygous variant (p.R14X c.40 C>T) for the IL-17RC gene.

White epidermal nevus as an early sign of tuberous sclerosis complex-A case series.

Tuberous sclerosis complex (TSC) is a rare genetic disease with neurocutaneous manifestations, often presenting initially to the dermatology clinic. We report a cohort of neonates who presented with a novel finding of white epidermal nevus and were eventually diagnosed with TSC. White epidermal nevus may be yet another dermatological finding that may aid in the early diagnosis of TSC.

Neonatal cutaneous inflammatory syndrome associated with homozygous epidermal growth factor receptor mutation.

The epidermal growth factor receptor (EGFR) is a transmembrane protein with tyrosine kinase signaling activity regulating many essential cellular functions, and loss of function mutations in EGFR result in a life-threatening neonatal syndrome. We present the case of a preterm boy born with intrauterine growth restriction who developed multisystem disease due to a homozygous mutation in the EGFR gene. He experienced a tumultuous and complex clinical course with recurrent skin infections and sepsis, nephrocalcinosis, failure to thrive, severe electrolyte imbalances, rectal perforation, and thrombus formation, and died after 11 months due to renal failure. This case report builds on work recently published in 2020 describing a case series of 18 similar patients and adds to the growing literature describing the severe phenotype and multisystem disease associated with loss of EGFR mutation in the Roma population.

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.

Alopecia and hyperpigmentation in a neonatal patient with lanosterol synthase gene deficiency and Spectrin alpha, non-erythrocytic 1 mutation.

Lanosterol synthase is required for cholesterol synthesis, and deficiencies have been associated with hypotrichosis as well as neuroectodermal syndromes including intellectual delay and epilepsy. Here, we report a case of lanosterol synthase deficiency in a 4-day-old patient who presented with alopecia and a previously unreported dermatologic manifestation of congenital localized hyperpigmentation.

Diagnostic outcomes from a combined Pediatric Dermatology-Genetics clinic.

Multispecialty clinics can be exceedingly helpful for diagnostically challenging and clinically complicated patients. This study highlights the diagnostic outcomes of the multispecialty Pediatric Dermatology-Genetics clinic at Children's Mercy-Kansas City over a 5-year period.

An unusual case of pediatric embryonal rhabdomyosarcoma with subsequent diagnosis of neurofibromatosis type 1.

A 10-month-old girl presented with a 4-month history of a rapidly growing lesion on the lower lip. Initial assessment and Doppler ultrasound supported a diagnosis of pyogenic granuloma. However, emergent biopsy revealed an embryonal rhabdomyosarcoma, a highly malignant tumor commonly associated with cancer-susceptible syndromes including neurofibromatosis type 1 (NF1). Despite having no apparent clinical features of NF1 at initial presentation, she was later found to have multiple café-au-lait spots and a subsequent diagnosis of NF1 was made.

Conradi-Hünermann-Happle syndrome associated with severe hypocalcemia in a newborn.

Conradi-Hünermann-Happle syndrome is rare X-linked dominant syndrome associated with stippled epiphyseal calcifications, congenital cataracts, Blaschkoid ichthyosiform scaling, and follicular atrophoderma. This case describes a novel finding of hypocalcemia and hypoparathyroidism in an infant with Conradi-Hünermann-Happle syndrome.

Identification of a novel variant of FOXP3 resulting in severe immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome highlights potential pitfalls of molecular testing.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genetic disorder that typically presents in the first year of life with severe diarrhea, autoimmune endocrine disorder, and inflammatory dermatitis, most commonly an eczematous dermatitis. IPEX syndrome is caused by variants in the FOXP3 gene leading to dysregulation of T-regulatory (Treg) cells and an aberrant immune response. Here, we present a case of severe IPEX syndrome diagnosed following whole genome sequencing (WGS) in a 2-week-old boy with bloody mucoid diarrhea, failure to thrive, and a diffuse eczematous dermatitis. As multiple variants of interest were identified with WGS, this case highlights the importance of relating the clinical symptoms to the genetic results.

Junctional epidermolysis bullosa with extensive lung involvement in three patients with a LAMB3 Mutation.

Junctional epidermolysis bullosa (JEB) is characterized by skin and mucous membrane fragility leading to easy blistering. Blistering may be the result of multiple genetic mutations, including the LAMB3 gene encoding a subunit of laminin 332, an important protein in the basement membrane zone. The clinical presentation of JEB includes blistering and granulation tissue forming anywhere on the skin including around oral and nasal cavities, fingers, toes, and within mucous membranes such as the upper respiratory tract. Lung pathology associated with JEB is less commonly reported; we describe three children with LAMB3 pathogenic variants with extensive lung injury contributing to decline in clinical status and likely leading to their demise early in life.

Cutaneous mastocytosis in a child with a de novo GNB1 mutation.

In the last few years, de novo mutations in the GNB1 gene have been found to cause a neurodevelopmental disorder typically characterized by global developmental delay and hypotonia. Only 4 cases of maculopapular cutaneous mastocytosis in children with GNB1 mutations have been reported to date. Here, we describe another case of the condition with concomitant cutaneous mastocytosis.

Novel CD63-PRKCB fusion in a case of pigmented epithelioid melanocytoma.

Pigmented epithelioid melanocytoma (PEM) is an intermediate-grade melanocytic tumor with considerable histologic overlap with other melanocytic neoplasms such as epithelioid blue nevus (EBN), which is associated with the neoplastic syndrome Carney complex (CC). Next-generation sequencing is a valuable tool for identifying the primary drivers of melanocytic neoplasms and differentiating them from one another. While germline variants in the protein kinase cAMP-dependent regulatory type 1 alpha (PRKAR1A) gene have been associated with EBN and CC, fusions in protein kinase C-alpha (PRKCA) have been shown as sporadic drivers of PEM. Herein, we report the diagnosis and workup of a case of pigmented epithelioid melanocytoma with a novel protein kinase C-beta (PRKCB) fusion.

Skin and Mucosal Manifestations in NEMO Syndrome: A Case Series and Literature Review.

OBJECTIVES: To characterize the skin and mucosal findings of NEMO syndrome. METHODS: Retrospective review of clinical characteristics from a cohort of two families with mutations in IKBKG (the NEMO-encoding gene). A literature review identified 86 studies describing 192 patients with IKBKG mutations whose data were also included. SETTING: Single center with literature review. PARTICIPANTS: Patients with mutations in IKBKG from our center and reported in the literature. MAIN OUTCOMES AND MEASURES: Skin and mucosal characteristics of patients with NEMO syndrome. RESULTS: In addition to ectodermal dysplasia and recurrent infections, male patients had findings of ichthyosis, palmoplantar keratoderma, and inflammatory skin diseases. Both male and female patients had mucocutaneous ulcers and slow-to-heal chronic wounds. In combination with patients from the literature, 59% (85/144) of males had ectodermal dysplasia with anhidrosis (EDA) features, and 8% and 10% (12/144; 6/63) of males and females had dental findings, respectively. 4% (6/144) of males and 32% (20/63) of females had mucocutaneous ulcers. Ichthyosis/xerosis was present in 15% of males (21/144) but only 2% (1/63) females. Similarly, 13% (18/144) of male patients presented with dermatitis while this was reported in only 2% (1/63) of females. CONCLUSIONS: Our results both confirm and expand upon the known spectrum of mucocutaneous findings in NEMO syndrome. Further genetic studies are needed to correlate specific mutations to clinical and morphologic subtypes.

Life-threatening hypothermia in a child with primary erythromelalgia.

Primary erythromelalgia is a rare autosomal-dominant condition due to pathogenic variant in the SCN9A gene, characterized by childhood onset of excruciating pain, redness, and warmth of acral sites. Patients often resort to ice water baths and other cooling measures to manage the discomfort. Hypothermia is a rare complication, reported only twice previously. We report a child with primary erythromelalgia due to a confirmed pathogenic variant admitted with life-threatening hypothermia. Although the overuse of cooling mechanisms may have contributed, we postulate that the SCN9A mutation may lead to thermodysregulation and make patients with primary erythromelalgia particularly susceptible to this complication.

Porokeratotic eccrine ostial and dermal duct nevus associated with an 11 megabase 3p deletion.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare eccrine hamartoma; the etiology is incompletely understood. A patient presented with congenital, widespread PEODDN. Clinical assessment, histopathologic, cytogenetic, and molecular genetic investigations on affected cells were pursued. Histopathology confirmed PEODDN, and chromosomal microarray on affected tissues identified a mosaic 3p26.3p25.3 deletion in affected tissues. This 11Mb deletion encompasses 47 OMIM genes. We propose that this and other chromosomal deletions may be implicated in some cases of PEODDN, suggesting locus heterogeneity and underscoring the importance of incorporating cytogenetic and molecular investigations into the multidisciplinary care of individuals with suspected mosaic genetic skin disorders.