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Ichthyotic disorders
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Conradi-Hünermann-Happle (CHH) syndrome is a rare X-linked dominant multisystem disorder. It occurs due to postzygotic mutation in the EBP (emopamil binding protein) gene on chromosome Xp11.23. It is characterized by linear ichthyosis, chondrodysplasia punctata, cataract, and short stature. The child is born with severe ichthyosiform erythroderma, and the scales are arranged in swirls and whorls along the lines of Blaschko. With age, ichthyosis improves and mild ichthyosis presents on the extremities along with follicular atrophoderma along the lines of Blaschko with hypopigmented and hyperpigmented streaks on the trunk. There may be persistent psoriasiform lesions in intertriginous areas (ptychotrophism) [15]. Localized scarring alopecia may be seen. Other features include asymmetrical skeletal involvement with stippled calcification of the epiphyseal region resulting in shortening of long bones, severe kyphoscoliosis, congenital dislocation of the hip, facial dysplasia, congenital heart defects, sensorineural deafness, renal anomalies, and ophthalmological changes like cataract, microphthalmia, and microcornea.
Cutting edge approaches to detecting brain mosaicism associated with common focal epilepsies: implications for diagnosis and potential therapies
Published in Expert Review of Neurotherapeutics, 2021
Zimeng Ye, Mark F. Bennett, Melanie Bahlo, Ingrid E. Scheffer, Samuel F. Berkovic, Piero Perucca, Michael S. Hildebrand
Identification of mosaic pathogenic variants is critical to take clinical management into the exciting arena of precision medicine. It leads to diagnostic certainty, alleviating a patient’s, or their family’s, concern about why they have epilepsy. Secondly, it informs precise genetic counseling about recurrence risk, or lack thereof, in the case of a post-zygotic mutation. Thirdly, molecular diagnoses can guide selection of existing therapies, such as sodium channel blockers (i.e. carbamazepine) to treat KCNQ2-related early onset epileptic encephalopathy, N-methyl-D-aspartate receptor antagonists (i.e. memantine) to treat GRIN2A-related early onset epileptic encephalopathy or potassium channel openers (i.e. quinidine) to treat KCNT1-related epilepsy of infancy with migrating focal seizures [34]. Determining a molecular diagnosis also provides opportunities for precise therapeutic trials of repurposed or novel drugs [34,72–75], such as mTOR inhibitors (i.e. everolimus) [72], as well as for use of emerging therapies, such as fenfluramine and cannabidiol [73–75].
Clinical diagnosis of presumed SOX2 gonadosomatic mosaicism
Published in Ophthalmic Genetics, 2021
Malena Daich Varela, Robert B. Hufnagel, Bin Guan, Delphine Blain, Julie C. Sapp, Andrea L. Gropman, Ramakrishna Alur, Jennifer J. Johnston, Leslie G. Biesecker, Brian P. Brooks
Mosaicism refers to a phenomenon in which a mutational event occurs post-conceptually, resulting in two or more different cell populations within the same individual (20). Depending on the timing of the post-zygotic mutation, mutant cells can be observed in different patterns. If the mutation occurs before left-right differentiation (in human, exact date unknown, but likely before five weeks of gestation; in mouse, around day 8 post-fertilization) (21), mutant cells populate both sides of the embryo, including the gonads. Mutations that happen after this point are typically unilateral and may show a striking respect for the midline when manifest on the skin. Another embryologic milestone is the differentiation of the primordial germ cells, which occurs by the 24th embryonic day in humans. If a mutation occurs after this point, it usually affects either the somatic or germinal lineage, not both. If the mosaicism hypothesis were correct in the family described here, the maternal variant in SOX2 must have occurred before the differentiation of the primordial germ cells (gonads and eyes affected), and even before left-right differentiation, (both eyes involved), but after or as a cause of the twinning event (only one twin affected) (22).
Monochorionic Twin Discordance for Horseshoe Lung and Tricuspid Atresia
Published in Fetal and Pediatric Pathology, 2022
Marina Sousa Gomes, José Monterroso, Otília Brandão, Carla Ramalho
In conclusion, the prognosis of a horseshoe lung is related to the associated cardiovascular valvular disease and not to the horseshoe lung itself. The discordance between monozygotic twins for horseshoe lung and tricuspid atresia raises the hypothesis that a postzygotic mutation, epigenetic or environmental factors may have a role in these malformations.