H syndrome: the first 79 patients

J Am Acad Dermatol. 2014 Jan;70(1):80-8. doi: 10.1016/j.jaad.2013.09.019. Epub 2013 Oct 27.


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.

Keywords: FHS; H syndrome; IDDM; OMIM; PHID; RDD; Rosai-Dorfman disease; SLC29A3; familial histiocytosis syndrome; genodermatosis; histiocytosis; hyperpigmentation; insulin-dependent diabetes mellitus; online Mendelian inheritance in man; pigmented hypertrichosis with insulin-dependent diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Contracture / genetics*
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Fingers
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Hyperpigmentation / genetics*
  • Hyperpigmentation / pathology
  • Hypertrichosis / genetics*
  • Hypertrichosis / pathology
  • Infant
  • Lymphatic Diseases / genetics
  • Male
  • Middle Aged
  • Mutation
  • Nucleoside Transport Proteins / genetics*
  • Skin Diseases, Genetic / genetics*
  • Skin Diseases, Genetic / pathology
  • Syndrome
  • Toes
  • Young Adult


  • Nucleoside Transport Proteins
  • SLC29A3 protein, human