Abstract: Central precocious puberty is the premature activation of the hypothalamic-pituitary-gonadal axis, leading to an early epiphyseal fusion and, in many cases, heights below the genetic target. Therefore, a proper adult stature prediction is essential for the treatment decision. Objective: To compare the concordance of final height using height prediction made by two validated methods versus the ge netic target height in girls who consulted due to central precocious puberty. Patients and Method: Retrospective, non-concurrent cohort study including 93 girls with central precocious puberty, who were not treated with LHRH analogs and had reached their final adult height. The data was obtained from the clinical records. To predict height, the Bayley-Pinneau method and the Roche-Wainer- Thissen method were applied, and the results were compared with the genetic target height. The concordance between the estimated final height and the final height obtained was evaluated using the Bland-Altman method. Results: When comparing the final height obtained with that predicted by the Bayley-Pinneau method, there was a mean difference of 1.01 cm, and using the Rocke-Wainer-Thissen method, there was a difference of +0.96 cm. The calculation of the genetic target height showed a difference of +0.05 cm with respect to the final height. Conclusion: The prediction of height made by the Bayley-Pinneau and Roche-Wainer-Thissen methods was adequate and, contrary to expectations, it was similar to the calculation of the genetic target height that does not use the age of bone maturation. This also presented better concordance and less dispersion of the results with respect to the final height obtained.

Resumen: La pubertad precoz central consiste en una activación prematura del eje hipotálamo-hipófisis-gonadal, lo que produce una fusión temprana del cartílago de crecimiento y, en muchos casos, una talla inferior al objetivo genético. Un adecuado pronóstico de estatura final es fundamental para definir el tratamiento. Objetivo: Comparar la concordancia de la talla final utilizando la predicción de la esta tura efectuada por dos métodos validados versus la talla diana o talla objetivo genético, en niñas que consultaron por pubertad precoz central. Pacientes y Método: estudio retrospectivo de cohorte no concurrente en el que participaron 93 niñas con pubertad precoz central no tratadas con análogos de LHRH y que alcanzaron su talla final. Los datos iniciales se obtuvieron de sus fichas clínicas. Para pre decir la talla se aplicaron los métodos más utilizados en la práctica clínica, Bayley-Pinneau y Roche- Wainer-Thissen, y luego se compararon los resultados con la talla objetivo genético. La concordancia entre la talla final estimada y la talla final obtenida se evaluó mediante el método de Bland y Altman. Resultados: Al comparar la talla final obtenida con la predicha por el método de Bayley-Pinneau se observó una diferencia promedio de 1,01 cm. Mediante el método de Roche-Wainer-Thissen, se observó una diferencia de +0,96 cm. El cálculo de la talla objetivo genético, arrojó una diferencia de +0,05 cm respecto a la talla final. Conclusión: La predicción de estatura realizada por los métodos Bayley-Pinneau y Roche-Wainer-Thissen fue adecuada, y contrario a lo esperado, fue similar al cálcu lo de la talla objetivo genético que no utiliza la edad de maduración ósea. Esta además presentó mejor concordancia y menor dispersión de los resultados respecto a la talla final obtenida.

O objetivo deste estudo foi descrever uma nova mutação no GNAS em uma família com pseudo-hipoparatireoidismo tipo Ia (PHP Ia), doença osteometabólica rara. Um garoto de oito meses foi visto por um endocrinologista por obesidade e baixa velocidade de crescimento. Chamava a atenção o fato de sua mãe apresentar fenótipo típico da osteodistrofia hereditária de Albright (OHA). O diagnóstico clínico de PHP Ia foi suspeitado. A região codificadora do GNAS da mãe e do filho foi amplificada e submetida ao sequenciamento direto. Uma nova mutação missense em heterozigose (c.673T>C) foi identificada no éxon 5 em ambos. O quadro clínico materno foi a pista para o diagnóstico do filho. A análise molecular do GNAS confirmou o diagnóstico de PHP Ia nos dois pacientes possibilitando o diagnóstico precoce da criança. Além disso, essa nova substituição missense expande o espectro de mutações no GNAS associadas a essa doença e permite o aconselhamento genético nesta família.

The objective of this study was to describe a new mutation in GNAS in a family with pseudohypoparathyroidism type Ia (PHP Ia), a rare osteometabolic disease. An 8-month-old boy was seen by an Endocrinologist due to obesity and low growth velocity. Noteworthy, his mother exhibited typical Albright hereditary osteodystrophy (AHO) phenotype. The clinical diagnosis of PHP Ia was suspected. The GNAS coding region from mother and son was amplified and directly sequenced. A novel heterozygous missense mutation (c.673T>C) was identified in exon 5 in both patients. In this family, the mother's clinical picture was the clue for the son's diagnosis. Molecular analysis of GNAS confirmed the diagnosis of PHP Ia in both patients and the child's early diagnosis was possible. Moreover, this novel missense substitution expands the spectrum of GNAS mutations associated with this disorder and allows for genetic counseling of this family.