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Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Differential diagnosis:Loeys-Dietz syndrome; probably the most similar condition, is characterised by generalised arterial tortuosity and aneurysms, cardiac defects and brain abnormalities; developmental delay can be present. Caused by mutations in the genes TGFBR1 and TGFBR2. Marfan syndrome (p. 534). Congenital contractural arachnodactyly, an autosomal dominant disorder caused by mutations in FBN2, does not show intellectual impairment or craniosynostosis. Homocystinuria caused by a deficiency of the enzyme cysthathionine synthetase, presents with a very similar phenotype and mental retardation but also subluxation of the lens and thrombophilia. Lujan–Fryns syndrome is an X-linked disorder also characterised by marfanoid habitus and mental delay but does not show craniosynostosis and joint contractures. Melnick-Needles syndrome (p. 130); frontometaphyseal dysplasia (p. 126).
Eye and ocular adnexa manifestations of MED12-related disorders
Published in Ophthalmic Genetics, 2022
Arth Shah, Monika Bapna, Hind Al-Saif, Rachel Li, Natario L. Couser
Background:MED12-related disorders are a rare group of intellectual disability syndromes, which involve disease-causing variants in the MED12 gene located on chromosome Xq13. This gene encodes the mediator complex subunit 12. The mediator complex is a unit composed of 25 proteins, and links transcription factors with RNA polymerase II, which is involved in transcription process. The mediator complex plays a role in transcriptional activation and repression of genes involved with the Wnt signaling pathway and SHH pathway, which are known to be crucial for embryonic cell differentiation and the developmental process (1). The syndrome was initially reported in a family of five affected males with intellectual disability, macrocephaly, and hypotonia, as described by John M. Opitz & Elisabeth G. Kaveggia, and was named FG Syndrome (OMIM #305450) using the Opitz system of using initials of the patients’ surname, also called Opitz-Kaveggia syndrome (2). This syndrome, in addition to Lujan-Fryns syndrome (OMIM #309520) and Ohdo syndrome (OMIM #300895) now represent a phenotypic spectrum of MED12-related disorders (3). Common findings within this spectrum include intellectual disability and characteristic craniofacial features. FG syndrome is characterized by macrocephaly, tall forehead, abnormal corpus callosum, downslanting palpebral fissures, small ears, broad thumbs, and hypotonia (4). Lujan-Fryns syndrome is characterized by cognitive impairment, macrocephaly, abnormalities of the corpus callosum, high narrow palate, short philtrum, thin body habitus, and hypotonia (5). Ohdo syndrome is characterized by intellectual disability, facial coarsening, and blepharophimosis (6). Additionally, there have been other less common phenotypes within the phenotypic spectrum; reported clinical features among these include retinal detachment, glaucoma, cataracts, and mild intellectual disability in heterozygous females (7,8).