Collagen VI-related disorders constitute a spectrum of severities from the milder Bethlem myopathy (BM) to the Ullrich congenital muscular dystrophy (UCMD), which is more severe, and an intermediate form characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in the ankles, elbows, knees, and spine in childhood.
View Article and Find Full Text PDFLesch-Nyhan syndrome (LNS) is a rare genetic disease secondary to a HPRT1 mutation on chromosome X. It is characterized by dystonia, developmental delay, hyperuricemia and self-harming behaviours. The HPRT enzyme is implicated in the purine salvage pathway.
View Article and Find Full Text PDFBackground: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. A progressive systemic skeletal chondrodysplasia, leading to significant morbidity and reduced life expectancy is the main clinical feature of this multisystemic disease. Although enzyme replacement therapy with elosulfase alfa is established in Europe, the rarity of disease and other factors still set hurdles in having patients treated in some countries.
View Article and Find Full Text PDFPurpose: Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed.
Methods: We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome.
Results: Computational facial and Human Phenotype Ontology-based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity.
Background: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients.
View Article and Find Full Text PDFNeurodegeneration with brain iron accumulation (NBIA) is a group of inherited disorders characterised by cerebral iron overload mainly in the basal ganglia. Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a form of NBIA caused by pathogenic C19orf12 gene variants. We report on a Romanian patient with MPAN confirmed through exome sequencing, revealing a homozygous nonsense variant in the C19orf12 gene, NM_001031726.
View Article and Find Full Text PDFBackground-Children with genetic disorders have multiple anatomical and physiological conditions that predispose them to obstructive sleep apnea syndrome (OSAS). They should have priority access to polysomnography (PSG) before establishing their therapeutic protocol. We analyzed the prevalence and the severity of OSAS in a particular group of children with genetic disorders and strengthened their need for a multidisciplinary diagnosis and adapted management.
View Article and Find Full Text PDFJuvenile segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ starting in childhood. Hutchinson-Gilford progeria syndrome (HGPS), caused by a recurrent de novo synonymous LMNA mutation resulting in aberrant splicing and generation of a mutant product called progerin, is a prototypical example of such disorders. Here, we performed a joint collaborative study using massively parallel sequencing and targeted Sanger sequencing, aimed at delineating the underlying genetic cause of 14 previously undiagnosed, clinically heterogeneous, non-LMNA-associated juvenile progeroid patients.
View Article and Find Full Text PDFDuring the last years, Down syndrome has been the focus of special attention. Down syndrome is a genetic disorder characterized by distinct physical features and some degree of cognitive disability. Patients with Down syndrome also present many other congenital anomalies.
View Article and Find Full Text PDFWe report the case of a 28-year-old female with progressive diaphyseal dysplasia, who presented with history of a similar neuromuscular condition. Clinical, radiological and molecular data confirmed Camurati-Engelmann Disease (CED). This is the first Romanian family who was diagnosed with CED.
View Article and Find Full Text PDFBruton's agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter's syndrome caused by an additional X chromosome is the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.
View Article and Find Full Text PDFJ Matern Fetal Neonatal Med
January 2014
Chromosome abnormalities represent the leading cause in many human genetic disorders. Gain or loss of genetic material can disrupt the normal expression of genes important in fetal development and result in abnormal phenotypes. Approximately 60% of first-trimester spontaneous abortions exhibit karyotype abnormalities.
View Article and Find Full Text PDFBackground: Tetrasomy 18p is a very rare chromosomal disorder and is the result of a spontaneous mutation early in embryonic development in most of the cases. This condition is characterised by the presence of a supernumerary 18p isochromosome (i(18p)) in all or some cells of the affected individual. It has a prevalence of 1/180000 live births and affects both genders equally.
View Article and Find Full Text PDFIntroduction: Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing.
Materials And Methods: In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department.