Verlust des Sensibilitäts- und Schmerzempfindens

The sensory nervous system detects pressure, touch, stretching, heat, and cold and translates these stimuli into action potentials. To protect the body from tissue damage acute pain is felt when a stimulus gains a critical intensity. The combination of impaired nociception and autonomic dysfunction is the hallmark of hereditary sensory and autonomic neuropathies (HSAN). Sensory loss in HSAN patients results in ulcerations of hands and feet and may necessitate amputations. Congenital onset of HSAN leads to self-mutilating behavior in affected children. Degeneration of motor neurons can complicate the disease. HSAN is divided into five groups according to clinical symptoms. So far, nine genes have been identified as causative for the disorder. The present article reviews the clinical, genetic, and pathophysiological aspects of HSAN.     

Mosaike bei monogenen Erkrankungen

Mosaicism is defined as the simultaneous presence of cells with different genotypes that originate from a common zygote. Mutations can either be present in germline or somatic cells. Monogenic disorders apparently caused by a de novo mutation may show a recurrence risk due to germline mosaicism in a parent. Duchenne muscular dystrophy is a well investigated example with a high frequency of germline mosaicism and the estimation for the risk of recurrence is based on theoretical models and empirical data. Recently, somatic mutations have been uncovered in various syndromic disorders, such as Proteus syndrome or hemimegalencephaly and respective mutations often show gain-of-function properties. Genetic testing is mainly based on next generation sequencing technologies but still remains challenging; however, detection of somatic mosaicism is expected to be of increasing relevance in the diagnosis of monogenic disorders. Somatic mosaicism may also play a hitherto underestimated role in common disorders.