ESPE Abstracts (2015) 84 P-2-451

SHOX Deficiency: Clinical, Radiological Signs and Value of Screening Scores

Giulia Genonia, Sandra Espositoa, Valentina Agarlaa, Alice Monzania, Matteo Castagnoa, Silvia Ravioloa, Antonella Petria, Flavia Prodama,b, Simonetta Bellonea,b & Gianni Bonaa

aDepartment of Health Sciences, Division of Pediatrics, University of Piemonte Orientale ‘A. Avogadro’, Novara, Italy; bEndocrinology, Department of Translational Medicine, University of Piemonte Orientale ‘A. Avogadro’, Novara, Italy

Objective and hypotheses: We studied the prevalence of deficiency in the short stature homeobox containing gene (SHOX) in short-statured children and analysed clinical and radiological signs.

Method: A total of 162 children aged 1–17 years (53% females, 67% prepubertal, median age 6.6 years, median height SDS −1.7) presenting with short stature between 2008 and 2014, were analysed for SHOX mutations by direct sequencing and multiplex ligation probe-dependent amplification analysis. Children with SHOX deficiency (SHOX-D) were compared to 1:2 age- and gender- matched children without SHOX deficiency with respect to radiological findings and anthropometrics.

Results: We identified 8 (4.9%) patients with SHOX-D and functionally relevant SHOX variations: one (12.5%) subject had a deletion, two children (25%) demonstrated a deletion in the enhancer domain, and five (62.5%) patients showed a point mutation in the coding region. The two groups did not differ with respect to height SDS, BMI SDS, or target height SDS. Subjects with SHOX mutations demonstrated significantly more frequently micrognathia. While none of the controls showed radiological signs, 25% of SHOX-D patients demonstrated Madelung deformity (P<0.05). The ratio of arm span to height did not significantly differ between the two groups while sitting height-to-height ratio was increased in SHOX-D children (P<0.05). The arm span to height ratio and the Rappold score showed the highest sensitivity to detect SHOX deficiency, while sitting height-to-height ratio demonstrated the best positive predictive value. The negative predictive values did not differ between the various scores. However, screening criteria would not identify some SHOX-D patients.

Conclusion: The phenotype of children with SHOX deficiency is highly variable. Moreover, clinical and radiological features are nonspecific or difficult to highlight, limiting their diagnostic value thus many subjects may be missed.

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