Withdrawal of iodinated disinfectants at delivery decreases the recall rate at neonatal screening for congenital hypothyroidism.

LetterSCOPUS: le.jinfo:eu-repo/semantics/publishe

GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1.

CONTEXT: KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE: Our objective was to identify deleterious mutations in KISS1. PATIENTS AND METHODS: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. RESULTS: Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.1-3659C→T) impairs transcription in vitro, and another (c.1-7C→T) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 ± 99, to double heterozygotes, 69 ± 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 ± 0.2 vs. 15.6 ± 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 ± 0.2 vs. 5.6 ± 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 ± 0.09 vs. 0.71 ± 0.06 litters/month, P < 0.04) and size (3.5 ± 0.2 vs. 5.4 ± 0.3 pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS: Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/−)/Kiss1r(+/−) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function

Supplementary Material for: Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal

<p><b><i>Background:</i></b> Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents. <b><i>Methods:</i></b> Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice communication with (i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young woman with 46,XY gonadal dysgenesis. The replies were analysed regarding completeness, quality, and evidence of empathy. Guidelines for structured assessment of responses were developed by 22 senior paediatric endocrinologists worldwide who assessed 10 selected replies. Consensus of assessors was established and the evaluation guidelines were created. <b><i>Results:</i></b> The replies of the fellows showed considerable variation in completeness, quality of wording, and evidence of empathy. Many relevant aspects of competent clinical communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies were considered poor/insufficient. There was also marked variation between 17 senior experts in the application of the guidelines to assess communication skills. The guidelines were then adjusted to a 3-level assessment with empathy as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators. <b><i>Conclusions:</i></b> E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD and their families and should be refined by all stakeholders, notably interdisciplinary health professionals and patient representatives.</p