The Head Circumference Height Index (HCH-I) to Quantify Relative Macrocephaly and Aid Identification of Hypochondroplasia in Children.

Abstract

Hypochondroplasia (HCH) is a rare skeletal dysplasia caused by pathogenic variants in the FGFR3 gene. We hypothesized that the relative disproportion between head circumference and height in HCH might be diagnostically informative and generated a simple index of head-stature disproportion to help pediatricians diagnose HCH. The Head Circumference Height Index (HCH-I), based on formal statistical principles, is defined as height Z-score - 1/2 head circumference Z-score, with the Z-scores based here on the UK90 growth reference. An HCH-I below the cut-off of -2 indicates substantial head-height disproportion. We validated the index by comparing children diagnosed with HCH (n = 364), using data from the recent European HCH growth charts, to children from the Cambridge Infant Growth Study (CIGS) (n = 4620). The mean (SD) HCH-I was -3.0 (1.2) in the HCH cohort, compared to -0.2 (0.9) in the CIGS cohort. An HCH-I below -2 correctly identified 78% of children with HCH, while only 2.4% of CIGS children fell below the cut-off. An HCH-I below -2 identifies children with head-height disproportion who may have HCH or another genetic disorder. The index is deliberately simple to calculate and should prove useful in clinical practice.