ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Novel Postzygotic Variants Associated With Hypomelanosis of Ito Expand the ACTB-Related Neurocutaneous Disease Spectrum.Clinical genetics · 2026Article
- A Case of Neonatal Hypomelanosis of Ito With Early-Onset Refractory Seizures and Cortical Malformations.Cureus · 2025Article
- A postzygotic GNA13 variant upregulates the RHOA/ROCK pathway and alters melanocyte function in a mosaic skin hypopigmentation syndrome.Nature communications · 2025Article
- Smith-Kingsmore syndrome with nystagmus as the initial symptom.Acta epileptologica · 2023Article
- Observation of a Possible Successful Treatment of DEPDC5-Related Epilepsy with mTOR Inhibitor.Neuropediatrics · 2023Article
- mTORC1 activity negatively regulates human hair follicle growth and pigmentation.EMBO reports · 2023Article
- Article
- A rare case of hypomelanosis of Ito with enlargement of Virchow-Rabin spaces in a 10-year-old child with symptoms of seizures.American journal of neurodegenerative disease · 2023Article
- Pigmentary mosaicism as a recurrent clinical manifestation in three new patients with mosaic trisomy 12 diagnosed postnatally: cases report and literature review.BMC medical genomics · 2022Review
- Review
- Correspondence on "Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities," by Carmignac et al.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
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Authors and funding
44 authors at 20 institutions in 3 countries.
Funding
Abstract
purposeHypomelanosis 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.
methodsFrom 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.
resultsMTOR 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.
conclusionMTOR-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.
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