upd(20)mat Syndrome

Maternal uniparental disomy of chromosome 20 syndrome (upd(20)mat)

Maternal uniparental disomy of chromosome 20 (upd(20)mat) has been reported in twelve patients [1], three of whom also had mosaicism for complete or partial trisomy of chromosome 20. All patients with upd(20)mat had intrauterine and postnatal growth retardation, and prominent feeding difficulties with failure to thrive often requiring gastric-tube feeding in the first few years of life. No dysmorphisms or congenital abnormalities or major developmental delay have been reported. So far, other types of molecular alterations have not yet been reported, and a candidate region on chromosome 20 has not yet been defined. It is striking that these patients have not been described to have features reminiscent of paternal GNAS loss of function mutations, although the loss of the paternal GNAS allele (on chromosome 20) is associated with pre- and post natal growth defect and Albright Hereditary Osteodystrophy. However, upd(20)mat probably presents a new imprinting disorder and its identification requires specialized molecular testing, which should be performed in patients with early-onset idiopathic isolated growth failure. In particular patients with a clinical diagnosis of SRS or TS14, but exclusion of their known molecular disturbances, are strong candidates for upd(20)mat as there appears to be significant phenotypic overlap.

References:

Mulchandani S, Bhoj E, Luo M, Powell-Hamilton N, Jenny K, Gripp K, et al. Maternal Uniparental Disomy of Chromosome 20: A Novel Imprinting Disorder of Growth Failure. Genet in Med: in press