[Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage]. / La pubertad en niños Chilenos muestra un adelantamiento en el inicio del crecimiento testicular.

BACKGROUND: A secular trend towards a younger age of puberty onset has been reported in Chilean girls. AIM: To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. MATERIAL AND METHODS: A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. RESULTS: Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. CONCLUSIONS: Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Primary Ovarian Failure in Addition to Classical Clinical Features of Coats Plus Syndrome in a Female Carrying 2 Truncating Variants of CTC1.

Coats plus syndrome is an autosomal recessive multisystemic and pleiotropic disorder affecting the eyes, brain, bone, and gastrointestinal tract, usually caused by compound heterozygous variants of the conserved telomere maintenance component 1 gene (CTC1), involved in telomere homeostasis and replication. So far, most reported patients are compound heterozygous for a truncating mutation and a missense variant. The phenotype is believed to result from telomere dysfunction, with accumulation of DNA damage, cellular senescence, and stem cell depletion. Here, we report a 23-year-old female with prenatal and postnatal growth retardation, microcephaly, osteopenia, recurrent fractures, intracranial calcification, leukodystrophy, parenchymal brain cysts, bicuspid aortic valve, and primary ovarian failure. She carries a previously reported maternally inherited pathogenic variant in exon 5 (c.724_727del, p.(Lys242Leufs*41)) and a novel, paternally inherited splice site variant (c.1617+5G>T; p.(Lys480Asnfs*17)) in intron 9. CTC1 transcript analysis showed that the latter resulted in skipping of exon 9. A trace of transcripts was normally spliced resulting in the presence of a low level of wild-type CTC1 transcripts. We speculate that ovarian failure is caused by telomere shortening or chromosome cohesion failure in oocytes and granulosa cells, with early decrease in follicular reserve. This is the first patient carrying 2 truncating CTC1 variants and the first presenting primary ovarian failure.

Pseudohypoparathyroidism type 1B associated with assisted reproductive technology.

Evidence suggests an increased incidence of imprinting disorders in children conceived by assisted reproductive technologies (ART). Maternal loss-of-methylation at GNAS exon A/B, observed in pseudohypoparathyroidism type 1b (PHP1B), leads to decreased expression of the stimulatory Gsα. We present a patient conceived by ART, who presented at age 4 years with delayed neurocognitive development and persistently increased creatine kinase (CK). At 6 years an elevated PTH was detected with normal calcium and a low 25(OH) vitamin D level (25OHD). Physical exam showed a narrow forehead, nasal bridge hypoplasia and micropenis. After normalizing vitamin D, PTH remained elevated and PHP1B was therefore considered as the underlying diagnosis. An almost complete loss-of-methylation was observed at GNAS exons A/B and AS, but not at exon XL, which was associated with a gain-of-methylation at exon NESP. There was no evidence of a microdeletion within the GNAS/STX16 region and analysis of several microsatellite markers for the GNAS region on Chr.20q revealed no evidence for paternal uniparental disomy (patUPD20q). Established facts Increased incidence of imprinting disorders in children conceived by assisted reproductive technologies (ART) Pseudohypoparathyroidism is caused by imprinting abnormalities. Novel Insights First report of a possible association between a methylation defects that causes PHP1B and assisted conception Increased creatine kinase level was associated with an increase in PTH concentration.

Talla baja: enfoque diagnóstico y bases terapéuticas / Short stature: diagnostic approach and therapeutic basis

La talla baja es un motivo de consulta cada vez más frecuente que el pediatra debe pesquisar. La evaluación debe incluir una historia clínica completa, examen físico con una correcta evaluación auxológica y un seguimiento adecuado de la velocidad de crecimiento. De esta forma, los exámenes complementarios irán orientados a confirmar una sospecha diagnóstica. En países desarrollados la mayoría de los pacientes que consulta por talla baja corresponderá a retraso constitucional del crecimiento o a una talla baja familiar, sin embargo, en alrededor de un 5% de los casos estaremos frente a patología como por ejemplo desnutrición, malabsorción, enfermedades sistémicas y sus tratamientos, déficit de hormona de crecimiento y enfermedades genéticas entre otras. El enfoque terapéutico, debe estar siempre orientado a la causa. Existen terapias que pueden mejorar la estatura final pero tienen indicaciones precisas y no están exentas de complicaciones. Un estilo de vida saludable y un ambiente psicosocial favorable, permitirán que el niño desarrolle al máximo su potencial genético.

Short stature is a complaint of increasing frequency in pediatrics. Given the diverse etiology of growth failure, the pediatrician must be able to make a correct assessment of the growth and development of children, including a complete medical history, physical examination and a proper auxological assessment with a carefully monitoring of their growth rate. This way, any further examination shall be designed to confirm a diagnostic suspicion. Although most patients will have an idiopathic short stature, in about 5% of cases we will find pathology. The therapeutic approach should always be oriented to the cause. There are therapies that can improve the final height but have precise indications and are not exempt from complications. A healthy lifestyle and a positive psychosocial environment, allow the child to develop his full genetic potential.

La pubertad en niños chilenos muestra un adelantamiento en el inicio del crecimiento testicular / Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage

Background: A secular trend towards a younger age of puberty onset has been reported in Chilean girls. Aim: To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. Material and Methods: A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Results: Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Conclusions: Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.