Longitudinal study of somatic development in Polish patients with Silver-Russell syndrome reveals that chest-to-head proportion as a new clinical indicator for the syndrome

Background Silver-Russell syndrome (SRS) is a rare congenital imprinting disorder associated with the loss of methylation in H19/IGF2 :IG-DMR at chromosome 11p15.5 (11p15 LOM) or maternal uniparental disomy of chromosome 7 (upd(7)mat). Methods Longitudinal analysis of somatic development was performed in 99 Polish patients with Silver-Russell syndrome: 82 (82.8%) with 11p15 LOM, 17 (17.2%) with upd(7)mat, without growth hormone therapy. All patients were assessed by a clinical geneticist and molecular tests were taken. Birth parameters were analyzed. Weight, height, BMI, and chest-to-head proportions were collected cross-sectionally and in different stages of development (every year, until the age of 16-18y). Results ROC analysis showed good diagnostic performance of head–chest proportionality indices in distinguishing SRS patients from SGA patients at birth. The difference between head and chest circumference demonstrated an AUC of 0.840 (95% CI 0.768–0.912), increasing to 0.850 (95% CI 0.771–0.929) after exclusion of preterm infants, while the chest-to-head ratio showed an AUC of 0.812 (95% CI 0.732–0.892) and 0.827 (95% CI 0.741–0.912), respectively. These simple indices, derived from routine neonatal measurements, may support early identification of SRS among SGA infants. Moreover chest-to-head circumference proportion in SRS patients does not change until the age of 9 years in boys and 8 years in girls. Long-term studies showed that body height, weight, weight-for-height, and BMI were higher in patients with 11p15LOM up to the age of 10-12; however, this trend reverses later in favor of the upd(7)mat group. Conclusion The introduction of head and chest circumference measurement into routine clinical examination may be useful, especially when the diagnosis of SRS is based solely on clinical symptoms. Long-term studies have shown a tendency for changes in body weight, height, and BMI depending on age and molecular abnormalities.