Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.

[wolf-hirschhorn syndrome]

Wolf-Hirschhorn syndrome (WHS ) is a well-known multiple congenital anomalies /mental retardation syndrome , firstly described in 1961 by Cooper and Hirschhorn . Its frequency is estimated as 1 /50 ,000 -1 /20 ,000 births , with a female predilection of 2 :1 . The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4 p 16 .3 ), and is considered a contiguous gene syndrome . No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype . Since the disorder was brought to the attention of geneticists , many additional cases have been published . Only in 1999 , however , were the first data on the natural history brought to the attention of the medical community . The purpose of the present study is to help delineate in more detail and over a longer period of time , the natural history of WHS , in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder . We have collected information on 87 patients diagnosed with WHS (54 females and 33 males ) both in USA and Italy . Age at first observation ranged between newborn and 17 years . Twenty patients have been followed from 4 months to 23 years . The deletion proximal breakpoint varied from 4 p 15 .32 to 4 p 16 .3 , and , by FISH , was terminal and included both WHSCR . Deletion was detected by standard cytogenetics in 44 /87 (50 .5 %) patients , whereas FISH was necessary in the other 43 (49 .5 %). Array-CGH analysis at 1 Mb resolution was performed in 34 /87 patients , and , in 15 /34 (44 %), showed an unbalanced translocation leading to both a 4 p monosomy and a partial trisomy for another chromosome arm . Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe . Sixty -five of 87 patients had an apparent pure , de novo , terminal deletion ; and 1 /87 a tandem duplication of 4 p 16 .1 p 16 .3 associated with 4 p 16 .3 pter deletion . Age at diagnosis varied between 7 months gestation and 16 years . Ninety -three percent had a seizure disorder with a good outcome ; 80 % had prenatal onset growth deficiency followed by short stature and slow weight gain ; 60 % had skeletal anomalies ; 50 % had heart lesions ; 50 % had abnormal tooth development ; and 40 % had hearing loss . Distinctive EEG findings were seen in 90 %. Structural CNS anomalies were detected in 80 %. Global developmental delay of varying degrees was present in all patients . Almost 50 % was able to walk either alone or with support . Hypotonia was present in virtually all patients . A global improvement was observed in all individuals , over time . Our survey has also shown how the characteristic facial phenotype tends to be less pronounced in those patients with a smaller deletion , and microcephaly is not observed in the patients with certain cryptic unbalanced translocations .

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Diseases presenting "specific probe" symptom

monosomy 21

wolf-hirschhorn syndrome

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