Disorder
Cohen syndrome

Clinical Characteristics

General description (for patients):

This disorder is clinically variable but within populations tends to be uniform.  Its primary features are mental retardation, general developmental delay, short stature, vision problems, obesity, floppiness, and a friendly disposition.  Children are slow to crawl, roll over, and talk with delayed walking and standing. The facial appearance may be distinctive with small mouth and jaw, a round tip of the nose, thick hair, and unusual eyelids with long lashes. The brain is often underdeveloped but there seems to be no progressive of the retardation.

Medical description (for healthcare providers):

Cohen syndrome is a global systemic disorder with CNS, hematologic, neuromuscular and ocular manifestations.  Short stature is common.  Some have truncal obesity and many have a characteristic facies with a friendly disposition.  The nasal bridge is low and the tip of the nose is bulbous.  Hypertelorism may be present and the eyelids may have a ‘wavy’ appearance with long eyelashes.  The mouth and jaw are often small.  Mild to moderate non-progressive mental retardation is characteristic and there is global developmental delay with hypotonicity and joint laxity.  Myopia and pigmentary retinopathy are common.  Some patients have neutropenia but immunologic deficiencies have not been reported.

Genetics:

This autosomal recessive disorder was initially described in 1973 and the mutant gene (COH1) was identified in 2003.  A number of mutations have been identified in Lebanese, Finnish, Belgian, Danish and British populations.  Among plain people, cases have been found only among the Geauga County, OH, Old Order Amish in which the COH1 gene on chromosome 8 (8q22-q23) contains two mutations (c.9258_9259insT and c.8459T>C).  All patients were homozygous for both mutations causing both a frameshift creating a premature stop codon, and an amino acid substitution.

Management:

No treatment for the genetic defect is available.  Supportive care and encouragement are required.

These individuals require lifelong supportive and custodial care.

Prognosis:

Most are easily assimilated into family life and generally function at a developmental age of 3-6 years.  Lifespan is unknown but most live at least to adulthood.

Specialists and specialty centers:

Neurologist, pediatrician, nutritionist

References:

Cohen, M.M. Jr., Hall, B.D., Smith, D.W, Graham, C.B., and Lampert, K.J.:  A new syndrome with hypotonia, obesity, mental deficiency, and facial, oral, ocular and limb anomalies.  J. Pediatr. 83: 280-284, 1973.  PubMed ID: 4717588

Falk, M.J.,  Feiler,  H.S.,  Neilson,  D.E.,  Maxwell,  K.,  Lee,  J.V.,  Segall,  S.K., Robin,  N.H.,  Wilhelmmsen, K.C.,  Traskelin,  A-L.,  Kolehmainen, J.,  Lehesjoki, A-E.,  Wiznitzer, M.,  and Warman, M.L.:   Cohen syndrome in the Ohio Amish.  Am. J. Med. Genet.  128A: 23-28, 2004.  PubMed  ID: 15211651

Kolehmainen,  J.,  Black,  G.C.M.,  Saarinen,  A.,  Chandler,  K.,  Clayton-Smith,  J., Traskelin, A-L.,  Perveen,  R.,  Kivitie-Kallio,  S.,  Norio, R., Warburg,  M.,  Fryns, J-P.,  de la Chapelle, A.,  and Lehesjoki,  A-E. :  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.  Am. J. Hum. Genet. 72:  1339-1369, 2003.  PubMed  ID: 12730828

Resources:

Cohen Syndrome
Cohen Syndrome Association