Titre : | SH3TC2-Related Hereditary Motor and Sensory Neuropathy : Synonyms: Charcot-Marie-Tooth Disease Type 4C, CMT4C, SH3TC2-HMSN, SH3TC2-Related Charcot-Marie-Tooth Neuropathy |
Revue : | GeneReviews® [Internet] |
Auteurs : | Azzedine H ; Salih MA |
Type de document : | Article |
Année de publication : | 11/03/2021 |
Langues: | Anglais |
Mots-clés : | article de type review ; CMT4C ; conseil génétique ; corrélation génotype-phénotype ; description de la maladie ; diagnostic ; diagnostic différentiel ; gène SH3TC2 ; neuropathie sensitivomotrice ; physiopathologie ; prévalence ; prise en charge thérapeutique ; SH3TC2 (maladie neuromusculaire liée à) |
Résumé : |
Initial Posting: March 31, 2008; Last Update: March 11, 2021.
Clinical characteristics. SH3TC2-related hereditary motor and sensory neuropathy (SH3TC2-HMSN) is a demyelinating neuropathy characterized by severe spine deformities (scoliosis or kyphoscoliosis) and foot deformities (pes cavus, pes planus, or pes valgus) that typically present in the first decade of life or early adolescence. Other findings can include cranial nerve involvement (most commonly tongue involvement, facial weakness/paralysis, hearing impairment, dysarthria) and respiratory problems. Diagnosis/testing. The diagnosis of SH3TC2-HMSN is established in a proband with suggestive findings and biallelic pathogenic variants in SH3TC2 identified by molecular genetic testing. Management. Treatment of manifestations: Treatment is symptomatic. Affected individuals are often managed by a multidisciplinary team that includes neurologists, physiatrists, orthopedic surgeons, physical and occupational therapists, audiologists/otolaryngologists, speech and language therapists, and pulmonologists. Surveillance: Routine follow up of motor and sensory manifestations, foot care, spine deformities, occupational and physical therapy needs, hearing, speech, and language therapy needs, and nutrition and growth. Agents/circumstances to avoid: Obesity, which makes walking more difficult; medications that are toxic or potentially toxic to persons with hereditary motor and sensory neuropathy. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger sibs of an affected individual in order to identify as early as possible those who would benefit from early detection and treatment of scoliosis as well as awareness of agents/circumstances to avoid. Genetic counseling. SH3TC2-HMSN is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SH3TC2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic SH3TC2 pathogenic variants and being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Because the carrier frequency for SH3TC2-HMSN in certain populations (e.g., individuals of Spanish Gypsy heritage) is relatively high and the onset of SH3TC2-HMSN may be late, some individuals who undergo carrier testing may be identified as being homozygous. Once the SH3TC2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing for SH3TC2-HMSN are possible. |
Lien associé : | Texte complet disponible en accès libre sur Bookshelf GeneReviews® |
Pubmed / DOI : | Pubmed : 20301514 |