Uncommon Large and Bilateral Fibrous Cephalic Plaques in a Patient with TSC2-Related Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a genetic disorder, frequently characterized by early dermatological manifestations. The recognition and adequate description of these dermatological manifestations are of utmost importance for early diagnosis, allowing for the implementation of therapeutic and preventive measures. Fibrous cephalic plaques (FCPs) are considered a major diagnostic criterion for TSC, as FCPs are the most specific skin lesions of TSC. The localization, consistency, color, and size of FCPs vary widely, which can cause diagnostic delay, especially in patients with atypical presentations. The present report describes a female TSC patient with a confirmed heterozygous pathogenic genotype, NG_005895.1 (TSC2_v001): c.2640-1G>T, who presented with uncommon large and bilateral FCPs causing bilateral ptosis and marked with hyperostosis of the diploe that generated an asymmetry of the brain parenchyma. Differential diagnoses considered initially in this patient due to the atypical FCPs are described.

Angelman Syndrome due to familial translocation: unexpected additional results characterized by Microarray-based Comparative Genomic Hybridization.

BACKGROUND: The 15q11q13 region is subject to imprinting and is involved in various structural rearrangements. Less than 1% of Angelman Syndrome patients are due to translocations involving 15q11q13. These translocations can arise de novo or result from the segregation of chromosomes involved in a familial balanced translocation. RESULTS: A 5-year-old Mexican girl presented with developmental delay, minor dysmorphic features and history of exotropia. G-banding chromosome analysis established the diagnosis of Angelman Syndrome resulting from a familial translocation t(10;15) involving the 15q11.2 region. The available family members were studied using banding and molecular cytogenetic techniques, including Microarray-based Comparative Genomic Hybridization, which revealed additional unexpected results: a coincidental and smaller 15q deletion, asymptomatic duplications in 15q11.2 and Xp22.31 regions. CONCLUSIONS: This report demonstrates the usefulness of array CGH for a detailed characterization of familial translocations, including the detection of submicroscopic copy number variations, which would otherwise be missed by karyotype analysis alone. Our report also expands two molecularly characterized rare patient cohorts: Angelman Syndrome patients due to familial translocations and patients with 15q11.2 duplications of paternal origin.