title: Delineation of dermatan 4-O-sulfotransferase 1 deficient Ehlers-Danlos syndrome: observation of two additional patients and comprehensive review of 20 reported patients.
abstract: Loss-of-function mutations in CHST14, dermatan 4-O-sulfotransferase 1 (D4ST1) deficiency, have recently been found to cause adducted thumb-clubfoot syndrome (ATCS; OMIM#601776) and a new type of Ehlers-Danlos syndrome (EDS) coined as EDS Kosho Type (EDSKT) [Miyake et al., 2010], as well as a subset of kyphoscoliosis type EDS without lysyl hydroxylase deficiency (EDS VIB) coined as musculocontractural EDS (MCEDS) [Malfait et al., 2010]. Lack of detailed clinical information from later childhood to adulthood in ATCS and lack of detailed clinical information from birth to early childhood in EDSKT and MCEDS have made it difficult to determine whether these disorders would be distinct clinical entities or a single clinical entity with variable expressions and with different presentations depending on the patients' ages at diagnosis. We present detailed clinical findings and courses of two additional unrelated patients, aged 2 years and 6 years, with EDSKT with a comprehensive review of 20 reported patients with D4ST1 deficiency, which supports the notion that these disorders constitute a clinically recognizable form of EDS. The disorder, preferably termed D4ST1-deficient EDS, is characterized by progressive multisystem fragility-related manifestations (joint dislocations and deformities, skin hyperextensibility, bruisability, and fragility; recurrent large subcutaneous hematomas, and other cardiac valvular, respiratory, gastrointestinal, and ophthalmological complications) resulting from impaired assembly of collagen fibrils, as well as various malformations (distinct craniofacial features, multiple congenital contractures, and congenital defects in cardiovascular, gastrointestinal, renal, ocular, and central nervous systems) resulting from inborn errors of development.
authors: Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan.
authors: Kenji
authors: K
authors: Shimizu
authors: Nobuhiko
authors: N
authors: Okamoto
authors: Noriko
authors: N
authors: Miyake
authors: Katsuaki
authors: K
authors: Taira
authors: Yumiko
authors: Y
authors: Sato
authors: Keiko
authors: K
authors: Matsuda
authors: Noriko
authors: N
authors: Akimaru
authors: Hirofumi
authors: H
authors: Ohashi
authors: Keiko
authors: K
authors: Wakui
authors: Yoshimitsu
authors: Y
authors: Fukushima
authors: Naomichi
authors: N
authors: Matsumoto
authors: Tomoki
authors: T
authors: Kosho
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003025:Clubfoot / Q000601:surgery; D019465:Craniofacial Abnormalities / Q000235:genetics; D003456:Cryptorchidism / Q000235:genetics; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology* / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D010641:Phenotype; D015238:Sulfotransferases / Q000172:deficiency* / Q000235:genetics
chemical_list: D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1