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Re: X-linked inheritance of Myhre syndrome is more likely than autosomal dominant.

Dear Editor

We read with interest the work by Burglen et al.[1]

We really appreciate their attempt to provide a careful differential diagnosis with other rare syndromes whose pathogenesis is still unknown. We observed one patient with Myhre syndrome [2] and another one affected by geleophysic dysplasia [3] and find their table 2 very useful in everyday clinical practice.

However, after their report of 4 more male patients with Myhre syndrome, we do not agree with their conclusion about the inheritance of the disease. They observe that paternal age was increased in half of the reported cases, suggesting a new mutation of an autosomal dominant gene. They also state that X linked transmission cannot be excluded since all reported cases (11/11) were males. The probability to observe 11 consecutive male patients is 1/2064, e.g. less than 5%, that is the usual value indicating statistical significance. Moreover, mean paternal age at birth is 35 years but the range is wide, varying from 23 to 43 years. So, we think that a X-linked pattern of inheritance is more likely in Myhre syndrome. That could be an important data to plan further investigation about the molecular basis of the disease. All reported cases are sporadic. So, a candidate gene approach is the only possibility to date. Our findings of abudant close-packed collagen fibers at skin biopsy could be a key-point to identify possible candidate genes involved in collagen metabolic pathway localized on the X chromosome. Understanding the pathogenesis of Myhre syndrome could provide further clues to identify the molecular basis of similar syndromes.

References

(1) L Burglen, D Héron, A Moerman, A Dieux-Coeslier, J-P Bourguignon, A Bachy, J-C Carel, V Cormier-Daire, S Manouvrier, A Verloes. Myhre syndrome: new reports, review, and differential diagnosis. J Med Genet 2003;40:546-551.

(2) Titomanlio L, Della Casa R, Lecora M, Farina V, Sebastio G, Andria G, Parenti G. Geleophysic dysplasia: 7-year follow-up study of a patient with an intermediate form. Am J Med Genet 1999; 86:82-5.

(3) Titomanlio L, Marzano MG, Rossi E, D’Armiento M, De Brasi D, Vega GR, Andreucci MV, Orsini AVM, Santoro L and Sebastio G. Case of Myhre syndrome with autism and peculiar skin histological findings. Am J Med Genet 2001;103:163-5.