Trisomy 5p is a chromosomal abnormality resulting from the duplication of a segment of variable size of the short arm of chromosome 5, which usually involves the distal band 5p15. The clinical presentation is variable but is always associated with severe intellectual deficit.
To date, more than 40 cases have been reported, the majority in association with another chromosomal anomaly.
Duplication of the 5p13 band determines the characteristic phenotype of trisomy 5p (the critical region): dolichocephaly or scaphocephaly with macrocephaly, oval elongated face, epicanthus, absent malar, long philtrum, ogival palate, macroglossia, dysplasic and low-set ears, micrognathia and short neck. Fingers are long. Patients may have microphthalmia or coloboma of the iris. At birth, the fontanelles are wide. Cerebral malformations (hydrocephalus, agenesis of the corpus callosum or Dandy-Walker malformation) are common. Visceral malformations are rare. Hypotonia is severe. There is a marked susceptibility to infections, especially respiratory infections, which can be life-threatening. Intellectual deficit is severe and may be accompanied by epilepsy. Larger duplications (up to the 5p11 band) have similar dysmorphisms, but more often are associated with failure to thrive, visceral and anorectal malformations, diaphragmatic hernia and club feet. Hydramnios may complicate pregnancy.
The duplication may extend towards the centromere, to the 5p11 band. The majority of reported patients have a large duplication, visible on the standard karyotype. Small subtelomeric duplications are rare. Duplications that extend to the 5p14 band result in variable intellectual deficit, epilepsy and a specific phenotype. There are no established correlations between genes in the critical region and the phenotype observed. In the majority of patients the 5p duplication is associated with the deletion of another chromosome as part of a translocation (familial or de novo). ``Pure'' duplications are rare. Some patients have been reported with interstitial duplication of 5p or an extra chromosome derived from the 5p arm (possibly in the form of a 5p isochromosome); these patients have a phenotype comparable to classical duplication.
Diagnosis is based on standard karyotyping or molecular determination of the karyotype (FISH, MLPA, CGH array).
In cases of de novo anomalies, the risk of recurrence is low and can be explained by the possibility of a mosaic germline parent.
Disease management does not differ from that of other patients with severe intellectual deficit and includes physical and psychomotor therapy. Respiratory infections should be treated aggressively.
The prognosis is poor; many patients die in childhood as a result of neurological complications or respiratory infections.
Last update: April 2009