Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.

Background: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving cause KBG syndrome, but no genotype-phenotype correlation has been reported.

Methods: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire.

First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center.

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease.

Coexistence of dyschondrosteosis associated to deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report.

We present an unusual case of deficiency associated with Léri-Weill dyschondrosteosis (LWD), Hashimoto's thyroiditis and pseudohypoparathyroidism 1B in a young woman. To our knowledge, this is the first ever report of these disorders coexisting. At the age of nine years, the proband was diagnosed of hypothyroidism due to Hashimoto's thyroiditis, and developed biochemical abnormalities consistent with hyperphosphatemia, mild hypocalcemia and elevated parathyroid hormone without any clinical symptoms except short stature.

Early-onset nucleotide excision repair disorders with neurological impairment: Clues for early diagnosis and prognostic counseling.

Nucleotide excision repair associated diseases comprise overlapping phenotypes and a wide range of outcomes. The early stages still remain under-investigated and underdiagnosed, even although an early recognition of the first symptoms is of utmost importance for appropriate care and genetic counseling. We systematically collected clinical and molecular data from the literature and from newly diagnosed NER patients with neurological impairment, presenting clinical symptoms before the age of 12 months, including foetal cases.

Correction to: Panel Discussion: Some Aspects of the Management of Patients with X-Linked Hypophosphataemic Rickets.

In the original article, there is an error in age related reference.

Correction to: Panel Discussion: Some Aspects of the Management of Patients with X-Linked Hypophosphataemic Rickets.

In the original article, third author name has been published incorrectly.

Panel Discussion: Some Aspects of the Management of Patients with X-Linked Hypophosphataemic Rickets.

X-linked hypophosphataemia (XLH) rickets is a rare disease frequently misdiagnosed and mismanaged. Despite having clinical guidelines that offers some therapeutic recommendations based on the clinical experience of experts, physicians still have questions about some important aspects of the diagnosis and treatment of XLH, such as when the disease should be suspected, who should be in charge of the diagnosis, what should be done once the disease is diagnosed, or what therapeutic options are currently available. The objective of this paper is to answer some of the more frequent questions related to the management of patients with XLH by a group of experts participating in a scientific conference on XLH held in Madrid.

A novel GLI2 mutation responsible for congenital hypopituitarism and polymalformation syndrome.

Objective: We report a novel GLI2 frameshift mutation and describe the phenotypic spectrum of mutations within this gene.

Patients And Methods: A male with congenital hypopituitarism and polymalformation syndrome was clinically, biochemically and neuroradiologically characterized. Genetic analysis for congenital hypopituitarism was performed using a targeted NGS custom gene panel.

A rare male patient with Fontaine progeroid syndrome caused by p.R217H de novo mutation in SLC25A24.

We report the clinical and genetic findings in a 15-year-old Spanish boy presenting prenatal and postnatal growth retardation, reduced subcutaneous adipose tissue, premature skin wrinkling, sparse hair, short distal phalanges with small nails, umbilical hernia, wide anterior fontanel, and normal cognitive and motor development. Exome sequencing uncovered a heterozygous mutation in SLC25A24 (NM_013386: c.650G>A: p.

Novel Dominant-Negative GH Receptor Mutations Expands the Spectrum of GHI and IGF-I Deficiency.

Context: Autosomal-recessive mutations in the growth hormone receptor (GHR) are the most common causes for primary growth hormone insensitivity (GHI) syndrome with classical GHI phenotypically characterized by severe short stature and marked insulin-like growth factor (IGF)-I deficiency. We report three families with dominant-negative heterozygous mutations in the intracellular domain of the causing a nonclassical GHI phenotype.

Objective: To determine if the identified heterozygous variants exert potential dominant-negative effects and are the cause for the GHI phenotype in our patients.

Chromosome 1p31.1p31.3 Deletion in a Patient with Craniosynostosis, Central Nervous System and Renal Malformation: Case Report and Review of the Literature.

Interstitial deletions in the short arm of chromosome 1 are infrequent. We report a female with a 1p31.1p31.

[Phenotypic variability of the 1q21.1 microdeletion syndrome in members of the same family: relevance of detection of neuropsychiatric disorders for diagnosis of genetic syndromes].

Introduction: 1q21.1 microdeletion syndrome is a caused by a recurrent deletion of the 1q21.1 copy-number variant, which spans 800 kb and includes at least seven genes.

Tumor-induced rickets in a child with a central giant cell granuloma: a case report.

Tumor-induced osteomalacia/rickets is a rare paraneoplastic disorder associated with a tumor-producing fibroblast growth factor 23 (FGF23). We present a child with symptoms of rickets as the first clinical sign of a central giant cell granuloma (CGCG) with high serum levels of FGF23, a hormone associated with decreased phosphate resorption. A 3-year-old boy presented with a limp and 6 months later with painless growth of the jaw.

Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study.

Unlabelled: Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height -1.

Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.

Craniosynostosis, caused by the premature fusion of one or more of the cranial sutures, can be classified into non-syndromic or syndromic and by which sutures are affected. Clinical assignment is a difficult challenge due to the high phenotypic variability observed between syndromes. During routine diagnostics, we screened 182 Spanish craniosynostosis probands, implementing a four-tiered cascade screening of FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1.

In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome.

Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism.

Individualised vs fixed dose of oral 17β-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial.

Context: Oestrogen induction of pubertal changes in Turner girls may reinforce their psychological well-being and may also optimise final height; however, oestrogen type, dose, and route are not well established.

Objective: To induce normal pubertal development in Turner girls and ovarian insufficiency with oral 17β-oestradiol (E(2)), either as individualised dose (ID) or as fixed dose (FD), and to determine whether growth is affected.

Design: Open-label randomised, parallel groups, multicentre clinical trial in 48 GH-treated Turner girls.

Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy.

Introduction And Objectives: Molecular characterization of congenital heart diseases now includes the not infrequent dysmorphic Noonan syndrome. A study of 6 genes of the RAS-MAPK pathway in Spanish patients is presented: the impact of heart disease, clinical expressivity, and diagnostic yield are investigated.

Methods: The study included 643 patients (and 182 family members) diagnosed by dysmorphologists, cardiologists, and pediatric endocrinologists from 74 tertiary hospitals.