MedGen

Carpal tunnel syndrome-1 (CTS1) is characterized by hand pain and numbness in the distribution of the median nerve, with onset in the sixth decade of life. Amyloid deposits are observed in synovial tissue of the wrist and in the transverse carpal ligament (Murakami et al., 1994). Genetic Heterogeneity of Carpal Tunnel Syndrome CTS2 (619161) is caused by mutation in the COMP gene (600310) on chromosome 19p13. Susceptibility to the development of mononeuropathy of the median (MNMN; 613353) may be conferred by heterozygous mutation in the SH3TC2 gene (608206) on chromosome 5q32. Carpal tunnel syndrome has been described as a feature in amyloid neuropathy (see 176300) and in mucopolysaccharidoses (e.g., 253200) and mucolipidoses (252600). [from OMIM]

Carpal tunnel syndrome is a disorder caused by disturbances in nerve function (neuropathy), leading to pain and numbness or tingling (paresthesia) primarily in the wrist and hand. While carpal tunnel syndrome can occur at any age, it most often affects people between the ages of 40 and 60. In more than half of cases, both hands are affected; however, the severity may vary between hands. When only one hand is affected, it is most often the hand used for writing (the dominant hand).

In carpal tunnel syndrome, the pain or paresthesia is usually felt in the wrist, the palm, and the first four fingers of the hand. These signs and symptoms often develop during sleep and are noticeable upon waking. Affected individuals typically shake their hand to get rid of the pain and numbness, a characteristic move known as the flick sign. As the condition advances, the signs and symptoms begin to occur during the day as well. Affected individuals may have difficulty performing manual tasks such as turning doorknobs, fastening buttons, or opening jars. The symptoms of carpal tunnel syndrome may be triggered by certain activities that flex or extend the wrist, such as driving, typing, or holding a telephone.

Over time, people with carpal tunnel syndrome can have muscle and nerve wasting (atrophy) in the affected hand and a reduced ability to detect sensations, which can be mistaken for an improvement of symptoms. [from MedlinePlus Genetics]

Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation. The vast majority of affected individuals are male; on rare occasion heterozygous females manifest findings. Age of onset, disease severity, and rate of progression vary significantly among affected males. In those with early progressive disease, CNS involvement (manifest primarily by progressive cognitive deterioration), progressive airway disease, and cardiac disease usually result in death in the first or second decade of life. In those with slowly progressive disease, the CNS is not (or is minimally) affected, although the effect of GAG accumulation on other organ systems may be early progressive to the same degree as in those who have progressive cognitive decline. Survival into the early adult years with normal intelligence is common in the slowly progressing form of the disease. Additional findings in both forms of MPS II include: short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepatosplenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome. [from GeneReviews]

Carpal tunnel syndrome-2 (CTS2) is characterized by the relatively early onset of symptoms of median nerve compression in the wrist. Patients experience pain and numbness in the thumb, index, and middle fingers, correlating with the median nerve distribution in the hand. In addition to thickening of the tendons and ligaments of the wrist, thickening of other tendons has been observed (Li et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of carpal tunnel syndrome, see CTS1 (115430). [from OMIM]

1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1.

Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication.

Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities. [from MedlinePlus Genetics]

Hereditary systemic amyloidosis-6 (AMYLD6) is an autosomal dominant systemic amyloidosis characterized by onset in middle age of gastrointestinal and cardiac symptoms resulting from progressive amyloid deposition. Neurologic involvement, sicca syndrome, and carpal tunnel syndrome may also be present (summary by Prokaeva et al., 2022 and Haslett et al., 2023). For a discussion of genetic heterogeneity of hereditary systemic amyloidosis, see AMYLD1 (105210). [from OMIM]

Injury to the median nerve caused by its entrapment at the wrist as it traverses through the carpal tunnel. Clinically, constrictive median neuropathy is characterized by pain, paresthesia, and weakness in the median nerve distribution of the hand. [from HPO]

A form of amyloidosis affecting patients with chronic kidney disease (CKD), on long term dialysis characterized by the accumulation of amyloid fibrils consisting of beta 2 microglobulin (β2M) deposits in the musculoskeletal system leading to carpal tunnel syndrome (CTS), chronic arthropathy, cystic bone lesions, destructive osteoarthropathy, and pathologic fractures. [from ORDO]

A rare rheumatologic disease characterized by bilateral morning stiffness which lasts > 45-60 min of duration associated with a subacute-onset of severe pain with active movements, typically affecting the shoulders, proximal upper limbs, neck and/or, less commonly, the pelvic girdle and proximal aspects of thighs, which are exacerbated with inactivity and improve progressively over the day. Muscle tenderness, peripheral synovitis, arthritis, carpal tunnel syndrome or distal tenosynovitis, as well as non-specific symptoms, such as fatigue, asthenia, malaise, low-grade fever, anorexia and weight loss, may be associated. Acute phase reactants (erythrocyte sedimentation rate, C-reactive protein) are increased. [from ORDO]

Disease involving the median nerve, from its origin at the brachial plexus to its termination in the hand. Clinical features include weakness of wrist and finger flexion, forearm pronation, thenar abduction, and loss of sensation over the lateral palm, first three fingers, and radial half of the ring finger. Common sites of injury include the elbow, where the nerve passes through the two heads of the pronator teres muscle (pronator syndrome) and in the carpal tunnel (carpal tunnel syndrome). [from MONDO]

A common form of systemic amyloidosis characterized by deposition of wild type transthyretin predominantly in the heart and the soft tissues (mainly the carpal tunnel region, lumbar canal and tendons). [from ORDO]

Localized lichen myxedematosus with monoclonal gammopathy or systemic symptoms is a form of atypical lichen myxedematosus, characterized by the appearance of several 2-4 mm erythematous waxy papules confined to a few sites that may be associated with either an immunoglobulin A (IgA) nephropathy in patients with acral persistent papular mucinosis; discrete papular lichen myxedematosus; a scleromyxedema-like involvement, with dysphagia, hoarseness, pulmonary involvement, and carpal tunnel syndrome; myositis without skin sclerosis; or paraproteinemia. [from MONDO]