Height, Head Circumference, Sitting Height, Leg Length, and Body Proportions Growth References to the Argentinian and Spanish Population for Hypochondroplasia

Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia caused by gain-of-function variants in FGFR3, leading to disproportionate short stature. Available growth references are limited, and body proportion data is lacking. We conducted a retrospective cohort study of 131 children with molecularly confirmed HCH (72 males, 59 females) from Argentina and Spain. Longitudinal anthropometric data (height, sitting height, head circumference) from birth to 18 years were analyzed. Leg length and body proportion indices were derived. Age- and sex-specific centiles were constructed using the LMS method. A total of 864 height, 660 sitting height, and 777 head circumference measurements were included. The majority of the individuals had the recurrent p.Asn540Lys FGFR3 variant (116/131). Birth size was significantly lower than reference standards. Height remained below the general population, with an overlap between the third centile of reference charts and the 90th-97th centiles of HCH. Sitting height showed a mild pubertal spurt, while leg length was markedly reduced without pubertal acceleration. Head circumference was normal but relatively increased for height. Body proportion indices confirmed disproportion from early life. These new growth references, including segmental and proportional indices, provide clinically relevant tools for monitoring growth and evaluating emerging therapies in HCH.