ESPE Abstracts

Introduction: Familial tall stature (FTS) is defined as height taller than +2 SD in a subject growing within his/her midparental height (MPH) with no apparent dysmorphic features. FTS is routinely not an indication for genetic investigation. However, some subtle dysmorphic features of various genetic disorders might be missed justifying the need for further investigation.

Aims: To elucidate the genetic cause of FTS and to reevaluate the syndromic features via detailed anthropometric examination.

Methods: Tall children with height > +2 SD, absence of intellectual disorder, no apparent dysmorphic features (those identified by routine endocrinological examination), absence of endocrine disease, unknown genetic cause of tall stature and taller parent’s height > +2 SD, who were referred to our outpatient clinic from September 2020 to March 2023, were enrolled to the study. In total, 29 children (17 girls) with FTS were enrolled in the study. Their median height was 3.07 SD (IQR 2.64 - 3.67 SD) and their age was 13 years (9 - 16 years). All subjects underwent routine examination by pediatric endocrinologist followed by detailed anthropometric examination. DNA samples were examined cytogenetically (karyotype and FISH) and via next-generation sequencing panel of 788 genes related to growth. The results were evaluated using American College of Medical Genetics and Genomics guidelines.

Results: We elucidated the genetic cause of tall stature in 10/29 (34.4%) children (genes NSD1 [2], FGFR3 [1], SUZ12 [2], PPP2R5D, SHOX duplication [2] and sex chromosome trisomy [2]). Moreover, by four subjects we found 4 variants of uncertain significance in genes FGFR1, FGFR3, TCF20, FBN2. Detailed anthropometric examination revealed subtle syndromic features in 6/10 subjects with positive genetic finding such as arachnodactyly (SUZ12), mild facial stigmatization (SHOX duplication), positive thumb and wrist sign and dolichocephaly (FGFR3), dolichocephaly and macrocephaly (NSD1), macrocephaly, positive thumb and wrist sign (PPP2R5D), dolichocephaly and high palate (NSD1).

Conclusion: Genetic causes traditionally associated with syndromic tall stature can be also found in children with FTS. Subtle syndromic features can be identified in these children by detailed anthropometric examination.

Acknowledgement: Supported by Ministry of Health of the Czech Republic, grant nr. NU21-07-00335.