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Hormone Research in Paediatrics 2020Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky... (Review)
Review
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.
Topics: Adult; Child; Diabetes Mellitus, Type 2; Dwarfism, Pituitary; Humans; Hypothyroidism; Practice Guidelines as Topic; Pseudohypoparathyroidism; Transition to Adult Care
PubMed: 32756064
DOI: 10.1159/000508985 -
Orthopaedics & Traumatology, Surgery &... Feb 2020Congenital pathologies of the forefoot encompass two broad entities with vastly different treatments and prognosis: malformations, which occur during the embryonic... (Review)
Review
Congenital pathologies of the forefoot encompass two broad entities with vastly different treatments and prognosis: malformations, which occur during the embryonic period and cause anatomical defects, and deformations, which occur during the fetal period on a foot that is configured normally. These deformities are more easily cured when they occur later during the fetal period. When the anomaly is bilateral, a genetic origin must be considered. There are two main entities under the term "deformity": metatarsus adductus and skewfoot (aka "Z"-foot or serpentine foot). Within malformations are brachydactyly (transverse defects), longitudinal defects, syndactyly, polydactyly, clinodactyly and macrodactyly. Among other forefoot abnormalities are hallux valgus, which rarely presents in congenital form, and for which conservative treatment is sometimes sufficient. Also in this group are sequelae of amniotic band constriction, forefoot anomalies secondary to the treatment of congenital pathologies (talipes equinovarus and congenital vertical talus) and nail-related pathologies (ingrown toe nail and incorrect nail position).
Topics: Child; Foot Deformities, Congenital; Global Health; Humans; Incidence; Metatarsal Bones; Radiography
PubMed: 31648997
DOI: 10.1016/j.otsr.2019.03.021 -
Reumatologia Clinica 2020Trichorhinophalangeal syndrome I (TPRSI) has an autosomal dominant inheritance; the proportion of «de novo» cases is unknown. It is characterized by unique facial...
Trichorhinophalangeal syndrome I (TPRSI) has an autosomal dominant inheritance; the proportion of «de novo» cases is unknown. It is characterized by unique facial features, bulbous nose, flat and elongated nasolabial furrow, thin hair and slow growth. Skeletal abnormalities that include short phalanges and metacarpals -brachydactyly-, cone-shaped epiphyses, hip dysplasia and short stature.
Topics: Female; Fingers; Hair Diseases; Humans; Langer-Giedion Syndrome; Male; Nose; Pedigree
PubMed: 30522940
DOI: 10.1016/j.reuma.2018.08.015 -
Human Mutation May 2020Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioral abnormalities, and seizures....
Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioral abnormalities, and seizures. Only 11 affected individuals have been reported to date, and the phenotype associated with pathogenic variants in this gene have not been fully defined. Here, we present 16 additional patients with predicted pathogenic heterozygous variants in including four individuals from the same family, to further delineate and expand the genotypic and phenotypic spectrum of ZMYND11-related syndromic intellectual disability. The associated phenotype includes developmental delay, particularly affecting speech, mild-moderate intellectual disability, significant behavioral abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, a depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip, and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia. Most identified variants are likely to result in premature truncation and/or nonsense-mediated decay. Two ZMYND11 variants located in the final exon-p.(Gln586*) (likely escaping nonsense-mediated decay) and p.(Cys574Arg)-are predicted to disrupt the MYND-type zinc-finger motif and likely interfere with binding to its interaction partners. Hence, the homogeneous phenotype likely results from a common mechanism of loss-of-function.
Topics: Alleles; Cell Cycle Proteins; Child; Child, Preschool; Co-Repressor Proteins; DNA-Binding Proteins; Facies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haploinsufficiency; Humans; Intellectual Disability; Male; Mutation; Nonsense Mediated mRNA Decay; Phenotype; Syndrome; Zinc Fingers
PubMed: 32097528
DOI: 10.1002/humu.24001