Compound Heterozygous Variants in a Patient with Severe Congenital Myopathy: Case Report and Comparison with Additional Cases of Recessive -Related Myopathy.

Pathogenic variants in the ryanodine receptor 1 () gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes.

Description of bone health in adolescents and young persons with Klinefelter syndrome - results from a pilot study.

Background: In adults with Klinefelter syndrome (KS), impaired bone health with reduced bone mineral density (BMD) has been described even in the presence of testosterone replacement therapy. The aim of the present study was to characterize bone health in young patients with KS.

Patients And Methods: 20 participants aged 16.

New Reference Values for Thyroid Volume by Ultrasound in German Children and Adolescents From a Population-Based Study.

Context: Reliable reference values for thyroid ultrasound measurements are essential to effectively guide individual diagnostics and direct population-level health care measures, such as iodine fortification programs. However, the latest reference values for total thyroid volume (Tvol) provided by the World Health Organization (WHO) in 2004 only apply to the 6- to 12-year-old age group and are limited to countries with a long history of iodine sufficiency, which does not reflect the situation in most European countries, including Germany.

Objective: This study aims to derive up-to-date thyroid volume ultrasound reference values in German children and adolescents.

ACOX1 Gain-of-Function Variant in Two German Pediatric Patients, in One Case Mimicking Autoimmune Inflammatory Disease.

Mitchell syndrome is a very rare genetic disorder due to a specific de novo gain-of-function variant in acyl-CoA oxidase 1 (). So far, only five patients with this disease have been described worldwide. We present here two additional unrelated German patients found to carry the same heterozygous  N237S variant through exome sequencing (ES).

Exome Sequencing and Optical Genome Mapping in Molecularly Unsolved Cases of Duchenne Muscular Dystrophy: Identification of a Causative X-Chromosomal Inversion Disrupting the Gene.

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to X-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, or point mutations in the dystrophin-encoding gene. However, in a small subset of patients clinically diagnosed with DMD, the molecular cause is not identified with these routine methods.

Cardiorespiratory fitness in adolescents and young adults with Klinefelter syndrome - a pilot study.

Background: Klinefelter syndrome (KS) may be associated with a wide spectrum of phenotypic changes including endocrine, metabolic, cognitive, psychiatric and cardiorespiratory pathologies in adults. However, in adolescence the clinical phenotype of KS is not well described, especially regarding physical fitness. The present study reports on cardiorespiratory function in adolescents and young adults with KS.

Subclinical Hypothyroidism and Incident Depression in Adolescents and Young Adults: Results from a Nationwide Representative Prospective Study.

Although the relationship between subclinical hypothyroidism and major depressive disorder (MDD) has been studied in adults in cross-sectional and prospective population-based studies, this has not yet been done in adolescents. However, since thyroid function and MDD risk are subjected to maturational processes and ramifications of illness duration over the life span, these findings may not readily transfer to adolescents. The relationship between subclinical hypothyroidism and MDD was studied in a representative subsample of the nationwide KIGGS ("The German Health Interview and Examination Survey for Children and Adolescents") survey.

Rhizomelia and Impaired Linear Growth in a Girl with Juvenile Paget Disease: The Natural History of the Condition.

In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway.

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) due to ENPP1-deficiency.

Awareness for hypophosphatemic rickets has increased in the last years, based on the availability of specific medical treatments. Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hypophosphatemic rickets, which is known to develop in survivors of generalized arterial calcification of infancy (GACI). Both disorders are based on a deficiency of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and present with a high clinical variability and a lack of a phenotype-genotype association.

No Effect of Thyroid Dysfunction and Autoimmunity on Health-Related Quality of Life and Mental Health in Children and Adolescents: Results From a Nationwide Cross-Sectional Study.

In adults, a significant impact of thyroid dysfunction and autoimmunity on health-related quality of life (HRQoL) and mental health is described. However, studies in children and adolescents are sparse, underpowered, and findings are ambiguous. Data from 759 German children and adolescents affected by thyroid disease [subclinical hypothyroidism: 331; subclinical hyperthyroidism: 276; overt hypothyroidism: 20; overt hyperthyroidism: 28; Hashimoto's thyroiditis (HT): 68; thyroid-peroxidase antibody (TPO)-AB positivity without apparent thyroid dysfunction: 61] and 7,293 healthy controls from a nationwide cross-sectional study ("The German Health Interview and Examination Survey for Children and Adolescents") were available.

Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis.

Background: Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood.

Novel Nonsense Mutation in Initially Presenting as Myopathy: Case Report and Review of the Literature.

Myopathies comprise a heterogeneous group of disorders characterized by variable phenotypes. The increasing use of next-generation sequencing allows identification of the causative genes in a much higher percentage of patients with hereditary muscle disorders and also illustrates a considerable degree of overlap with other clinical entities, including connective tissue disorders. Here, we present a 14-year-old German patient who was initially suspected to suffer from myopathy based on his clinical, radiological, and muscle biopsy findings.

Prospective Evaluation of Predictive DNA Testing for Huntington's Disease in a Large German Center.

We present a prospective study of counselees seeking predictive testing for Huntington's disease at the Huntington Center North Rhine-Westphalia (Bochum, Germany) between 2010 and 2012. The aim was to observe the decision-making process of at-risk individuals and explore their experiences following the decision as well as the impacts of positive and negative mutation results. Data were collected using two standardized questionnaires as well as via a semi-standardized telephone interview one year after the initial counseling session.

A Novel ECM1 Splice Site Mutation in Lipoid Proteinosis: Case Report plus Review of the Literature.

Lipoid proteinosis (LP) is an autosomal recessive genodermatosis known to be caused by mutations in ECM1. Nonsense and missense mutations are the most common variations in LP. Up to date, only 6 splice site mutations have been observed.

WDR45 mutations in Rett (-like) syndrome and developmental delay: Case report and an appraisal of the literature.

Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood. Recent reports suggest that WDR45 mutations are associated with a broader phenotypic spectrum. We identified a novel splice site mutation (c.

Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia.

The hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative diseases. Here, we evaluated the spectrum and frequency of mutations in the CYP7B1, PNPLA6 and C19orf12 genes (causative for the subtypes SPG5A, SPG39 and SPG43, respectively) in a cohort of 63 unrelated HSP patients with suspected autosomal recessive inheritance. Two novel homozygous mutations (one frameshift and one missense mutation) were detected in CYP7B1 (SPG5A), while no disease-causing mutation was identified for SPG39 or SPG43.