Broader geographical spectrum of Cohen syndrome due to COH1 mutations

Changing facial phenotype in Cohen syndrome: towards clues for an earlier diagnosis

“…If neutrophil count is performed in patients with developmental delay and shows neutropenia, CS can be suspected; CRD, when evidenced, reinforces CS suspicion but it is present in only about half of the patients in this period of life. 12,13,15,16,18,22,23 Interestingly, in our series, 2 out of 17 patients did not display typical facial features even with advancing age (P24-F18 and P25-F18) ( Figure 5). In P25-F18, the grimacing expression of the face was present, but there were no photographs showing this specific expression, demonstrating that it can be very difficult to raise a diagnosis of CS on photographs alone.…”

“…In all patients CRD or myopia was present. 12,13,15,16,18,22,23 Thus, CS early diagnosis in late infancy and early preschool age (2-5 years) is a real challenge for physicians. We therefore searched for clues that could improve the detection of CS in childhood by describing the facial phenotype of 17 patients with a molecular diagnosis of CS from infancy onwards.…”

“…1,7,8 To date, the late appearance of certain clinical signs have been the main cause of delay in the diagnosis. [12][13][14][15][16] Indeed, in preschool age (3-to o6 years) and even more in infants o3 years of age, the facial characteristics are less noticeable: 3,8,17 for example, CRD is either not yet apparent on fundus examination or rarely investigated by electroretinography except when severe clinical visual disturbances are present, and neutropenia can be present but is rarely screened for, or even considered, in the absence of clinical manifestations. The goal of this study was to describe the facial features in the beginning of life, including the preschool period, and to analyse their evolution with advancing age to find clues for an earlier diagnosis, in a series of 17 patients with molecularly confirmed CS.…”

Clinical and molecular characterization of Italian patients affected by Cohen syndrome

“…Convex The frameshift mutation p.Q721fs744X and the nonsense mutation p.R2707X, both leading to premature protein interruption were found in case 7. The frameshift mutation p.Y3855fs3877X was identified in case 8, in which a partial gene deletion in the other allele has been found (Falk et al 2004;Hennies et al 2004;Kolehmainen et al 2003;Mochida et al 2004;Seifert et al 2006). Patient 7 was 6 years old at assessment and presented wave-shaped eyelids, a hypotonic facial expression with an open mouth (picture not reported).…”

“…More recently, Cohen syndrome was found to be associated with mutations in the COH1 gene in different populations with a broader clinical spectrum than the Finnish subtype (Falk et al 2004;Hennies et al 2004;Kolehmainen et al 2003;Mochida et al 2004;Seifert et al 2006). To clarify the clinical and molecular features associated with Cohen syndrome in the Italian population, we describe here 10 patients from nine Italian families in which COH1 mutations have been identified.…”