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Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome

OMIM ID:

autosomal dominant

Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome

Alternate Names

HLTRS
glomerulonephritis with sparse hair and telangiectases
telangiectatic membranoproliferative glomerulonephritis

Defective Genes

SOX18

Clinical Characteristics

Ocular Features

Sparse hair can be noted at birth and by several years of age the alopecia of the eyelids and eyebrows is complete.  The upper eyelids may be swollen at birth as well. 

Systemic Features

The facial features are unusual.  The nose appears long and may have a broad nasal root.  The lips are full and the lower jaw is prominent. Evidence of developmental delay has been reported in one patient.

The scrotum can be edematous at birth and sometimes contains large hydroceles.  Hair is sparse in infancy but within a few years alopecia is complete.  Telangiectases on the scalp, scrotum, and limbs are evident at several years of age.  Pulmonary vascular congestion and lymphangiectasia may be present in some individuals antenatally.  Renal failure, sometimes with hypertension can occur at any time from early childhood to young adulthood.  Renal biopsy has shown histologic features consistent with membranoproliferative glomerulonephritis and thrombotic microangiopathy.  This may be preceded by proteinuria in infants as young as 2 years. 

Genetics

Inheritance

This condition is the result of heterozygous mutations in the SOX18 gene (20q13.33). 

Homozygous mutations in the same gene may be responsible for a somewhat similar disorder (HLTS) (607823) which has many of the same facial and systemic features but lacks the renal disease. 

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

Some patients have benefitted from renal transplantation.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

Dominantly inherited glomerulonephritis and an unusual skin disease.

PubMedID: 3435166

Hypotrichosis‐lymphedema‐telangiectasia‐renal defect associated with a truncating mutation in the SOX18 gene

PubMedID: 24697860