lymphedema

Takenouchi-Kosaki Syndrome

Clinical Characteristics
Ocular Features: 

The ocular phenotype consists of mild ptosis, synophrys, exotropia, and eversion of the lower eyelids.  One of two reported patients was described as having bilateral retinal dysplasia and a falciform retinal detachment in one eye.  Visual acuity is significantly impaired.

Systemic Features: 

Affected individuals may be of normal birth weight but skeletal growth is subnormal and there is general developmental delay.  Congenial cardiac anomalies such as persistent ductus arteriosus may be present.  Lymphedema has been noted at one year of age and probably persists throughout life.  Protein-losing enteropathy secondary to intestinal lymphangiectasia was present in one individual.  The same patient had pericardial effusion, hydrothorax, and ascites.  Intellectual disability may be severe although there is no evidence of progression.  Neurosensory hearing loss has been described in one patient.

Thrombocytopenia is a consistent finding and has been described as early as one year of age.  Platelet numbers as low as 52,000/microL have been recorded and appear larger than normal. 

Genetics

Both unrelated female patients reported have heterozygous missense mutations in the CDC42 gene (1p36). 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome

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

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
Treatment
Treatment Options: 

Some patients have benefitted from renal transplantation.

References
Article Title: 

Lymphedema-Distichiasis Syndrome

Clinical Characteristics
Ocular Features: 

This form of lymphedema is associated with distichiasis, often with trichiasis and significant corneal damage in about 75% of patients.  Onset of symptoms may occur at any age but usually during childhood or adolescence.  Photophobia, epiphora, corneal erosions, ptosis, and partial ectropion of the lids may also be seen.  The secondary symptoms of trichiasis are not always present and slit lamp examination of the lashes may be necessary to see the duplicated row of lashes.  The lashes often grow out of the Meibomian orifices.

Systemic Features: 

Cardiac defects, cleft palate, and spinal extradural cysts occur in some families.  Type II diabetes and interstitial nephritis have been reported.  The lymph channels in the lower extremities may be normal or increased in number, especially below the knee where pitting edema is most often first seen, even as early as the first decade of life.  Lymphedema occurs earlier in males and secondary cellulitis is a greater risk. It is usually confined to the lower extremities and is often asymmetrical.  Not all patients have the complete syndrome, while lymphedema and distichiasis can be inherited as individual disorders without being associated.  Males are more likely to have the complete syndrome.

Several families with this syndrome secondary to mutations in the FOXC2 have been reported to have renal anomalies ranging from kidney agenesis to malrotation. 

Genetics

This disorder is inherited in an autosomal dominant pattern and several families have been found to have mutations in the FOXC2 gene on chromosome 16 (16q24.3).  A Chinese family with an affected father and two affected offspring (one male and one female) has been reported with distichiasis but no lymphedema.  A premature stop codon was found in the FOXC2 transcription gene (16q24.1) in these family members suggesting that they may have had the lymphedema-distichiasis syndrome instead.

Blatt distichiasis is a unique disorder without the lymphedema (126300). 

Double rows of eyelashes are also part of the blepharocheilodontic syndrome (119580).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Electrolysis of individual misdirected lashes can be applied.  Prompt treatment of lid cellulitis is important. Surgical repair of scarred lid tissue can restore cosmesis lid function and improve cosmesis.

References
Article Title: 

Renal anomalies and lymphedema distichiasis syndrome

Jones GE, Richmond AK, Navti O, Mousa HA, Abbs S, Thompson E, Mansour S, Vasudevan PC. Renal anomalies and lymphedema distichiasis syndrome. A rare association? Am J Med Genet A. 2017 May;173(8):2251-2256.

PubMed ID: 
28544699

Hereditary lymphedema and distichiasis

Kolin T, Johns KJ, Wadlington WB, Butler MG, Sunalp MA, Wright KW. Hereditary lymphedema and distichiasis. Arch Ophthalmol. 1991 Jul;109(7):980-1.

PubMed ID: 
2064580
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