RESUMEN
Klinefelter's syndrome, the most common sex disorder associated with chromosomal aberrations, is characterized by a plethora of clinical features. Parameters for diagnosis of the syndrome are constantly expanding as new anatomical and hormonal abnormalities are noted, yet Klinefelter's remains underdiagnosed and underreported. This review outlines the key anatomical characteristics associated with the syndrome, which are currently used for clinical diagnosis, or may provide means for improving diagnosis in the future. Clin. Anat. 29:606-619, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Síndrome de Klinefelter/patología , Enfermedades del Sistema Endocrino/etiología , Fertilidad , Humanos , Síndrome de Klinefelter/complicaciones , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/psicología , Tamizaje Masivo , Enfermedades Musculoesqueléticas/etiología , Diagnóstico Prenatal , Caracteres SexualesRESUMEN
Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation, involving Chromosome 15. The phenotypical appearance of individuals with the syndrome follows a similar developmental course. During infancy, universal hypotonia accompanied by feeding problems, hypogonadism, and dolichocephaly are evident. Characteristic facial features such as narrow bifrontal diameter, almond-shaped eyes, and small mouth (with downturned corners and thin upper lip) may also be evident at this stage. In early childhood, the craniofacial features become more obvious and a global developmental delay is observed. Simultaneously, individuals develop hyperphagia that leads to excessive or rapid weight gain, which, if untreated, exists throughout their lifespan and may predispose them to numerous, serious health issues. The standard tool for differential diagnosis of PWS is genetic screening; however, clinicians also need to be aware of the characteristic features of this disorder, including differences between the genetic subtypes. As the clinical manifestations of the syndrome vary between individuals and become evident at different developmental time points, early assessment is hindered. This article focuses on the clinical and anatomical manifestations of the syndrome and highlights the areas of discrepancy and limitations within the existing literature. Clin. Anat. 29:590-605, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Síndrome de Prader-Willi/patología , Dentición , Facies , Humanos , Hipopigmentación/etiología , Anomalías Musculoesqueléticas/etiología , Fenotipo , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/fisiopatología , Visión OcularRESUMEN
Skeletal muscle development has been the focus of intensive study for many decades. Recent advances in genetic manipulation of the mouse have increased our understanding of the cell signalling involved in the development of muscle progenitors which give rise to adult skeletal muscles and their stem cell populations. However, the influence of a vital tissue type - the peripheral nerve-has largely been ignored since its earliest descriptions. Here we carefully describe the timing in which myogenic progenitors expressing Pax3 and Pax7 (the earliest markers of myogenic cells) enter the limb buds of rat and mouse embryos, as well as the spatiotemporal relationship between these progenitors and the ingrowing peripheral nerve. We show that progenitors expressing Pax3 enter the limb bud one full day ahead of the first neurites and that Pax7-expressing progenitors (associated with secondary myogenesis in the limb) are first seen in the limb bud at the time of nerve entry and in close proximity to the nerve. The initial entry of the nerve also coincides with the first expression of myosin heavy chain showing that the first contact between nerves and myogenic cells correlates with the onset of myogenic differentiation. Furthermore, as the nerve grows into the limb, Pax3 expression is progressively replaced by Pax7 expression in myogenic progenitors. These findings indicate that the ingrowing nerve enters the limb presumptive muscle masses earlier than what was generally described and raises the possibility that nerve may influence the differentiation of muscle progenitors in rodent limbs.
Asunto(s)
Esbozos de los Miembros/embriología , Esbozos de los Miembros/inervación , Desarrollo de Músculos/fisiología , Músculo Esquelético/embriología , Músculo Esquelético/inervación , Unión Neuromuscular/embriología , Animales , Diferenciación Celular/genética , Embrión de Mamíferos , Femenino , Regulación del Desarrollo de la Expresión Génica , Esbozos de los Miembros/metabolismo , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Unión Neuromuscular/genética , Unión Neuromuscular/metabolismo , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Embarazo , Ratas , Ratas WistarRESUMEN
This work investigates the role of NT-3 in peripheral myelination. Recent articles, based in vitro, propose that NT-3 acting through its high-affinity receptor TrkC may act to inhibit myelin formation by enhancing Schwann cell motility and/or migration. Here, we investigate this hypothesis in vivo by examining myelination formation in NT-3 mutant mice. On the day of birth, soon after the onset of myelination, axons showed normal ensheathment by Schwann cells, no change in the proportion of axons which had begun to myelinate, and no change in either myelin thickness or number of myelin lamellae. However in postnatal day 21 mice, when myelination is substantially complete, we observed an unexpected reduction in mRNA and protein levels for MAG and P(0), and in myelin thickness. This is the opposite result to that predicted from previous in vitro studies, where removal of an inhibitory NT-3 signal would have been expected to enhance myelination. These results suggest that, in vivo, the importance of NT-3 as a major support factor for Schwann cells (Meier et al., (1999) J Neurosci 19:3847-3859) over-rides its potential role as an myelin inhibitor, with the net effect that loss of NT-3 results in degradation of Schwann cell functions, including myelination. In support of this idea, Schwann cells of NT-3 null mutants showed increased expression of activated caspase-3. Finally, we observed significant reduction in width of the Schwann cell periaxonal collar in NT-3 mutant animals suggesting that loss of NT-3 and resulting reduction in MAG levels may alter signaling at the axon-glial interface.