This rare disorder is an autosomal recessively inherited congenital overgrowth syndrome with phenotypic similarities to Beckwith–Wiedemann syndrome. Affected children are large at birth and hypotonic and have organomegaly, characteristic facial dysmorphisms (inverted V-shape upper lip, prominent forehead, deep-set eyes, broad flat nasal bridge, low set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality (Perlman 1986; Greenberg et al. 1988). Perlman syndrome is associated with a very high risk of Wilms Tumours (64 % incidence in infants surviving beyond the neonatal period), an earlier age at diagnosis than in sporadic cases (<2 years and 3–4 years, respectively), and a high frequency of bilateral Tumours (55 %).
Histological examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis (an important precursor lesion for Wilms Tumours).
Perlman syndrome is caused by germline inactivating mutations in DIS3L2 (a homologue of the yeast Dis3 gene). Dis3 is a critical component of the evolutionarily conserved exosome complex, and it has been suggested
that the inactivation of DIS3L2 leads to disordered RNA metabolism with aberrant expression of mitotic checkpoint proteins (Astuti et al. 2012; Greenberg et al. 1986).