Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex

Vascular Anomalies in Otolaryngology-Head and Neck Surgery Resident Education

The evaluation and treatment of vascular anomalies is rapidly evolving. In recent years, improved imaging, medical therapies, interventional radiology procedures, and technical advances have led to improved functional and aesthetic outcomes with reduced morbidity. With management of vascular anomalies becoming increasingly complex, we wanted to assess the opinions of otolaryngology-head and neck surgery resident trainees regarding education in this evolving subspecialty. The results of our survey show that a significant majority of trainees feel that vascular anomalies are best managed by a multidisciplinary team, consistent with practice in large vascular anomalies centers. While training in this area does not seem to be deficient, it may be helpful to identify those otolaryngology residents who are interested in gaining exposure to patients with vascular anomalies, so that they may seek additional subspecialty experiences to complement their otolaryngology training

Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome

BACKGROUND—In adults, erythema multiforme (EM) is thought to be mainly related to herpes infection and Stevens-Johnson syndrome (SJS) to drug reactions.
AIMS—To investigate this hypothesis in children, and to review our experience in the management of these patients.
METHODS—A retrospective analysis of 77 paediatric cases of EM or SJS admitted to the Children's Hospital in Bordeaux between 1974and 1998.
RESULTS—Thirty five cases, inadequately documented or misdiagnosed mostly as urticarias or non-EM drug reactions were excluded. Among the remaining 42 patients (14 girls and 28 boys), 22 had EM (11EM minor and 11 EM major), 17 had SJS, and three had isolated mucous membrane involvement and were classified separately. Childhood EM was mostly related to herpes infection and SJS to infectious agents, especially Mycoplasma pneumoniae. Only two cases were firmly attributed to drugs (antibiotics). No patient died. EM and SJS sequelae were minor and steroids were of no overall benefit.
CONCLUSION—In paediatric practice EM is frequently misdiagnosed. The proposal that SJS is drug related in adults does not apply to children, and in our recruitment EM and SJS are mostly triggered by infectious agents. The course of both diseases, even though dramatic at onset, leads to low morbidity and mortality when appropriate symptomatic treatment is given.