Maternal uniparental disomy 14 dissection of the phenotype with respect to rare autosomal recessively inherited traits, trisomy mosaicism, and genomic imprinting

The phenotype of maternal uniparental disomy of chromosome 14 (upd(14)mat) is characterized by pre and postnatal growth retardation, early onset of puberty, joint laxity, motor delay, and minor dysmorphic features of the face, hands, and feet. Based on a clinical analysis of 24 cases extracted from the literature the phenotype of upd(14)mat was dissected with respect to each symptom’s most likely primary causative: trisomy mosaicism, rare autosomal recessively inherited traits, and the impact of known imprinted genes located on chromosome 14q32. As a result, primary factors are confined placental mosaicism for prenatal growth retardation and one or more imprinted genes, which contribute to the reduced final height by accelerated skeletal maturation. As a secondary effect the latter might also cause early onset of puberty. Other secondary effects might be postnatal adaptation problems associated with neurological deficits such as muscular hypotonia due to premature delivery and reduced birthweight and most dysmorphic features as a consequence of subtle skeletal abnormalities and muscular hypotonia. Considering the rarity of traits such as cleft palate, trisomy mosaicism in the fetus is more likely causative than homozygosity of autosomal recessively inherited mutations. Totally, the variable phenotype of upd(14)mat is mainly the consequence of trisomy mosaicism and genomic imprinting. Rare traits might be due to homozygosity of autosomal recessively inherited mutations.