TGM1related

TGM1-related refers to disorders caused by pathogenic variants in the TGM1 gene, which encodes transglutaminase-1, an epidermal enzyme that catalyzes cross-linking of structural proteins during the formation of the cornified cell envelope. The TGM1 gene is located on chromosome 14q11 and is predominantly expressed in the skin.

Genetically, TGM1-related conditions are inherited in an autosomal recessive manner. Affected individuals typically harbor biallelic mutations, including missense, nonsense, splice-site, and frameshift variants, which reduce or abolish enzyme activity. Carrier frequencies vary by population, and some groups have founder mutations that contribute to regional prevalence.

The principal clinical manifestation is TGM1-related autosomal recessive congenital ichthyosis (ARCI). Newborns may present with a collodion membrane and, as it evolves, generalized ichthyosis with thick scales or erythroderma. Phenotypes range from severe, persistent scaling with barrier impairment to milder presentations. Common features include dry, scaly skin and fissures, with potential secondary issues such as heat intolerance or recurrent skin infections; some patients may have eyelid involvement or other skin and hair findings. The condition is lifelong and requires ongoing dermatologic care.

Diagnosis is established by clinical assessment supported by genetic testing confirming biallelic TGM1 variants. Skin biopsy is not diagnostic, and there is no routine functional test used in standard care beyond research settings.

Management focuses on improving the skin barrier and preventing complications. Treatments include regular emollients, keratolytics, and careful use of retinoids in selected cases, along with measures to prevent overheating and manage infections. Genetic counseling is recommended, given the autosomal recessive inheritance and implications for family planning. TGM1 mutations are a common cause of ARCI in many populations, underscoring the importance of genetic confirmation for prognosis and management.