Abstract：A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G > A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
Cohen MM Jr, Hall BD, Smith DW, et al. A new syndrome with hypotonia, obesity, mental deficiency, and facial, oral, ocular, and limb anomalies[J]. J Pediatr, 1973, 83:280-284.
[2]
Kolehmainen J, Wilkinson R, Lehesjoki AE, et al. Delineation of Cohen syndrome following a large-scale genotype-phenotype screen[J]. Am J Hum Genet, 2004, 75(1):122-127.
[3]
Chandler KE, Kidd A, Al-Gazali L, et al. Diagnostic criteria, clinical characteristics, and natural history of Cohen syndrome[J]. J Med Genet, 2003, 40(4):233-241.
[4]
Kivitie-Kallio S, Norio R. Cohen syndrome:essential features, natural history, and heterogeneity[J]. Am J Med Genet, 2001, 102(2):125-135.
[5]
Katzaki E, Pescucci C, Uliana V, et al. Clinical and molecular characterization of Italian patients affected by Cohen syndrome[J]. J Hum Genet, 2007, 52(12):1011-1017.
[6]
Taban M, Memoracion-Peralta DS, Wang H, et al. Cohen syndrome:report of nine cases and review of the literature, with emphasis on ophthalmic features[J]. J AAPOS, 2007, 11(5):431-437.
[7]
Coppola G, Federico RR, Epifanio G, et al. Focal polymicrogyria, continuous spike-and-wave discharges during slow-wave sleep and Cohen syndrome:a case report[J]. Brain Dev, 2003, 25(6):446-449.
[8]
Kolehmainen J, Black GC, Saarinen A, et al. Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport[J]. Am J Hum Genet, 2003, 72(6):1359-1369.
[9]
Seifert W, Holder-Espinasse M, Kühnisch J, et al. Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1[J]. Hum Mutat, 2009, 30(2):E404-E420.
[10]
Seifert W, Kühnisch J, Maritzen T, et al. Cohen syndrome-associated protein, COH1, is a novel, giant Golgi matrix protein required for Golgi integrity[J]. J Biol Chem, 2011, 286(43):37665-37675.
[11]
Duplomb L, Duvet S, Picot D, et al. Cohen syndrome is associated with major glycosylation defects[J]. Hum Mol Genet, 2014, 23(9):2391-2399.
[12]
Seifert W, Kühnisch J, Maritzen T, et al. Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth[J]. J Biol Chem, 2015, 290(6):3349-3358.
[13]
Massa G, Dooms L, Vanderschueren-Lodeweyckx M. Growth hormone deficiency in a girl with the Cohen syndrome[J]. J Med Genet, 1991, 28(1):48-50.
[14]
Kivitie-Kallio S, Rajantie J, Juvonen E, et al. Granulocytopenia in Cohen syndrome[J]. Br J Haematol, 1997, 98(2):308-311.
[15]
Seow WK, Bartold PM, Thong YH, et al. Cohen syndrome with neutropenia-induced periodontitis managed with granulocyte colony-stimulating factor (G-CSF):case reports[J]. Pediatr Dent, 1998, 20(5):350-354.
