H syndrome: The first 79 patients

Background H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. Objective We sought to investigate the clinical and molecular findings in 79 patients with this disorder. Methods A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. Results The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3 , with no genotype-phenotype correlation. Limitations In the 31 patients described by others, data were collected from the medical literature. Conclusions H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3 -related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients.