ABSTRACT
Mosaic mutations in genes GNAQ or GNA11 lead to a spectrum of diseases including Sturge-Weber syndrome and phakomatosis pigmentovascularis with dermal melanocytosis. The pathognomonic finding of localized "tramlining" on plain skull radiography, representing medium-sized neurovascular calcification and associated with postnatal neurological deterioration, led us to study calcium metabolism in a cohort of 42 children. In this study, we find that 74% of patients had at least one abnormal measurement of calcium metabolism, the commonest being moderately low serum ionized calcium (41%) or high parathyroid hormone (17%). Lower levels of ionized calcium even within the normal range were significantly associated with seizures, and with specific antiepileptics despite normal vitamin D levels. Successive measurements documented substantial intrapersonal fluctuation in indices over time, and DEXA scans were normal in patients with hypocalcemia. Neurohistology from epilepsy surgery in five patients revealed not only intravascular, but perivascular and intraparenchymal mineral deposition and intraparenchymal microvascular disease in addition to previously reported findings. Neuroradiology review clearly demonstrated progressive calcium deposition in individuals over time. These findings and those of the adjoining paper suggest that calcium deposition in the brain of patients with GNAQ/GNA11 mosaicism may not be a nonspecific sign of damage as was previously thought, but may instead reflect the central postnatal pathological process in this disease spectrum.
Subject(s)
Calcinosis , Neurocutaneous Syndromes , Child , Humans , GTP-Binding Protein alpha Subunits/genetics , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , Calcium/metabolism , Mosaicism , Neurocutaneous Syndromes/diagnosis , Neurocutaneous Syndromes/genetics , Calcinosis/geneticsSubject(s)
Keratinocytes/immunology , Molecular Biology , Molecular Targeted Therapy/methods , Nevus, Sebaceous of Jadassohn/genetics , Nevus, Sebaceous of Jadassohn/therapy , Biopsy , CARD Signaling Adaptor Proteins/genetics , Case-Control Studies , Child , Child, Preschool , Connexin 43/genetics , Female , Guanylate Cyclase/genetics , Humans , Infant , Inflammation , Keratinocytes/metabolism , Male , Membrane Proteins/genetics , Mosaicism , Mutation, Missense , Treatment OutcomeSubject(s)
Neutropenia/diagnosis , Neutropenia/etiology , Rothmund-Thomson Syndrome/diagnosis , Rothmund-Thomson Syndrome/etiology , Skin Abnormalities/diagnosis , Skin Abnormalities/etiology , Alleles , Diagnosis, Differential , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Mutation , PhenotypeABSTRACT
Keratinocytic epidermal nevi (KEN) are characterized clinically by permanent hyperkeratosis in the distribution of Blaschko's lines and histologically by hyperplasia of epidermal keratinocytes. KEN with underlying RAS mutations have been associated with hypophosphatemic rickets and dysplastic bone lesions described as congenital cutaneous skeletal hypophosphatemia syndrome. Here, we describe two patients with keratinocytic epidermal nevi, in one associated with a papular nevus spilus, who presented with distinct localized congenital fibro-osseous lesions in the lower leg, diagnosed on both radiology and histology as osteofibrous dysplasia, in the absence of hypophosphatemia or rickets, or significantly raised FGF23 levels but with distinct mosaic HRAS mutations. This expands the spectrum of cutaneous/skeletal mosaic RASopathies and alerts clinicians to the importance of evaluating for bony disease even in the absence of bone profile abnormalities.
Subject(s)
Hypophosphatemia , Keratosis , Nevus , Skin Neoplasms , Epidermis , Fibroblast Growth Factor-23 , Humans , Keratinocytes , Nevus/genetics , Skin Neoplasms/diagnosis , Skin Neoplasms/geneticsABSTRACT
Psoriasis is one of the most common chronic skin diseases, affecting 1%-3% of the general population. It can have a significant negative impact on a patient's quality of life, and in approximately 30% of patients first symptoms can be traced back to childhood. We have performed a comprehensive literature search using the MEDLINE database in order to ascertain the efficacy and adverse reactions of topical treatments in pediatric psoriasis. A total of 13 relevant articles were identified on the following topical agents: corticosteroids, calcineurin inhibitors, vitamin D analogs, and dithranol. Corticosteroids achieved clearance in 72.7% of patients. Calcitriol lead to a 57.2%-100% mean improvement in severity, and calcipotriol to 52%-64%. Combination of calcipotriol and corticosteroids achieved an improvement in mean severity ranging between 32.1% and 80%. Treatment with tacrolimus lead to an >50% improvement. Finally, short contact dithranol lead to a variable response in clearance between different studies, ranging between 3.7% and 81%. No serious adverse reactions were documented, the most common local reaction being irritation. Pediatric psoriasis is a common and challenging condition with no easy and definitive solution. Topical agents are safe, easy to use, readily available and cheap. However, they need to be applied repeatedly, may cause skin irritation, and can be messy. Based on the results presented above, we recommend utilizing all the available topical options before escalating to systemic treatments.
