MedGen

MPV17-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. MPV17-related mtDNA maintenance defect, encephalohepatopathic form is characterized by: Hepatic manifestations (liver dysfunction that typically progresses to liver failure, cholestasis, hepatomegaly, and steatosis); Neurologic involvement (developmental delay, hypotonia, microcephaly, and motor and sensory peripheral neuropathy); Gastrointestinal manifestations (gastrointestinal dysmotility, feeding difficulties, and failure to thrive); and Metabolic derangements (lactic acidosis and hypoglycemia). Less frequent manifestations include renal tubulopathy, nephrocalcinosis, and hypoparathyroidism. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported. [from GeneReviews]

Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease. [from GeneReviews]

Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease. [from GeneReviews]

Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.

The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed. [from MedlinePlus Genetics]

Marsili syndrome (MARSIS) is an autosomal dominant pain insensitivity disorder characterized by a lowered ability to sense pain, to experience temperature, and to sweat. Affected individuals do not perceive broken bones and burns as painful, and have lowered sensitivity to capsaicin. However, visceral pain (e.g., childbirth-related) and light touch are perceived (summary by Habib et al., 2018). [from OMIM]

An increased tendency to fractures following trauma, with fractures occurring without pain. [from HPO]