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Differential Diagnosis
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Hemant Kumar Kar, Gunjan Verma
Vitiligo should be differentiated from Waardenburg syndrome, which is also an autosomal dominant disorder with a similar clinical presentation. It is associated with heterochromia iridis, dystopia canthorum, congenital deafness, and occasionally a congenital megacolon (Hirschsprung disease). Waardenburg syndrome is an expression of a neurocristopathy, involving not only the melanocytes in the skin but also those at the level of the eyes, hair, cochlea, and meninges. Four subtypes have been identified. Piebaldism is comparable to these depigmented macules. However, the predominantly ventral distribution of the lesions, congenital character, stable course, white forelock, and the presence of hyperpigmented maculae within the areas of depigmentation are suggestive for piebaldism [6].
New Aspects of Isotretinoin Teratogenicity
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
DiGeorge syndrome, a 22q11.2 deletion syndrome, is another neurocristopathy resembling retinoid embryopathy (83). The most studied gene of interest in the 22q11.2 deletion region is TBX1, encoding a T-box transcription factor (83). Tbx1-/- mice had a high incidence of cardiac outflow tract anomalies, hypoplasia of the thymus and parathyroid glands, abnormal facial structures, abnormal vertebrae, and cleft palate, leading to the conclusion that Tbx1 in humans is a key gene in the etiology of DiGeorge syndrome (84–86). Tbx1 controls cardiac NCC migration during arch artery development by regulating GBX2 expression in the pharyngeal ectoderm (87). Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice (86). In accordance, half dosage of this gene in humans causes most of the features of the DiGeorge or velocardiofacial syndrome phenotypes, including aortic arch and cardiac outflow tract abnormalities (88). Recently, a strong genetic interaction between Tbx1 and p53 has been found. Intriguingly, genetic ablation of TP53, or pharmacological inhibition of p53, rescues significantly the cardiovascular defects of Tbx1 heterozygous and hypomorphic mutants (88). As a result, disturbed Tbx1-p53 signaling is involved in the pathogenesis of DiGeorge syndrome.
Waardenburg syndrome
Published in Electra Nicolaidou, Clio Dessinioti, Andreas D. Katsambas, Hypopigmentation, 2019
Carmen Maria Salavastru, Stefana Cretu, George Sorin Tiplica
The neural crest was first described over 150 years ago.9 WS is a typical neurocristopathy and its characteristics are due to mutations affecting neural crest cells. These multipotent embryonic cells migrate from the dorsal part of the neural tube and are precursors for several cell lineages: melanocytes, peripheral and enteric neurons and glia, craniofacial chondrocytes, osteoblasts, adrenal chromaffin cells, intermediate cells of the stria vascularis in the cochlea, and certain cells of the heart and thymus.10–12 All melanocytes, except for those of the retina (derived from the optic cup of the brain), are derived from cells of the neural crest.9,12 The function of the protein products of the mutated genes can be absent or diminished compared to the wild-type gene, depending on the mutations present and on how much of the original protein was altered.13 The features present in WS are the result of a reduced level of expression (haploinsufficiency) of different transcription factors.12 This results in anomalies of the proliferation, survival, migration, and differentiation of the cells derived from the neural crest. These cells, at key moments in their development, express specific genes.
Harboyan syndrome with biallelic SLC4A11 pathogenic variants misdiagnosed as congenital CMV infection
Published in Ophthalmic Genetics, 2022
Cam Loveridge-Easther, Gulunay Kiray, Sarah Hull, Andrea L. Vincent
CHED is characterised by diffuse ground glass corneal oedema and thickening of Descemet membrane, and presents in two forms (6–8). CHED1 tends to be autosomal dominant and less severe, while CHED2 is autosomal recessive and usually more severe (7). CHED is nearly always present at birth, may be associated with glaucoma, isolated or syndromic, and is considered a neurocristopathy resulting from a failure of regression of the primordial endothelium during development of the anterior chamber (7,9). This results in a spectrum of disease with severe failure of regression resulting in CHED and minor failure resulting in posterior polymorphic membrane dystrophy, a milder, related but separate clinical entity (9). The preferred treatment of CHED is penetrating keratoplasty which can provide significant vision improvement (8).
Advances in the molecular biology and pathogenesis of congenital central hypoventilation syndrome—implications for new therapeutic targets
Published in Expert Opinion on Orphan Drugs, 2018
Simona Di Lascio, Roberta Benfante, Silvia Cardani, Diego Fornasari
As the PHOX2B gene plays an important role in the development of the ANS, CCHS is defined as a generalized ANS disorder caused by the defective migration and/or differentiation of neural crest derivatives (neurocristopathy). It may be isolated or associated with other conditions reflecting ANS dysregulation, including tumors originating from the sympathetic nervous system such as neuroblastomas, ganglioneuromas, and ganglioneuroblastomas, autonomic dysfunctions of the enteric nervous system, such as the aganglionic megacolon Hirschsprung’s disease (HSCR; the association of CCHS and HSCR is known as ‘Haddad syndrome’; MIM# 209880), and/or milder intestinal phenotypes (gastroesophageal reflux, constipation) and symptoms that can be attributed to the defective differentiation of the neural crest cells (cardiac arrhythmias and ocular disorders) [1,3,14].
The presence and progression of choroidal neurofibromas in a predominantly pediatric population with neurofibromatosis type-1
Published in Ophthalmic Genetics, 2021
Corina M. Chilibeck, Shaheen Shah, Heather C. Russell, Andrea L. Vincent
Neurofibromatosis type-1 (NF1) is a progressive multisystem disorder affecting 1:3500 births, due to autosomal dominant pathogenic variants in the NF1 tumor suppressor gene, resulting in abnormal neurofibromin (1). Considered a neurocristopathy, it affects cells that are neural-crest in origin (1) and approximately 50% of cases are thought to be from spontaneous mutations (2). The most commonly reported ocular feature of NF1 is iris hamartomas, also known as Lisch nodules, but other manifestations include optic pathway gliomas, orbital and plexiform palpebral neurofibromas, periocular café-au-lait spots, and choroidal neurofibromas (2).