Table 2.

Disorders to Consider in the Differential Diagnosis of Lymphedema-Distichiasis Syndrome (LDS)

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/LDSDistinguishing from LDS
Milroy disease FLT4 ADLymphedema 1
  • Typically congenital-onset lymphedema (very rarely presents later)
  • Absence of distichiasis
Meige disease
(OMIM 153200)		UnknownAD
  • Absence of distichiasis
Hypotrichosis-lymphedema-telangiectasia syndrome
(OMIM 607823)		 SOX18 AR
  • Loss of hair
  • Telangiectasia, particularly in the palms
  • Absence of distichiasis
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
(OMIM 137940)		AD
Lymphedema microcephaly
(OMIM 152950)		 KIF11 AD
  • Small head circumference
  • May be associated w/chorioretinopathy &/or ID
  • Absence of distichiasis
Yellow nail syndrome
(OMIM 153300)		UnknownAD 2
  • Very slow-growing nails w/transverse overcurvature & hardening of the nail plate 3
  • Absence of distichiasis
Emberger syndrome
(OMIM 614038)		 GATA2 AD
  • Myelodysplasia
  • Immunodeficiency
  • Absence of distichiasis
Blepharocheilodontic syndrome
(OMIM PS119580)		 CDH1
CTNND1 		ADDistichiasis 4
  • Lagophthalmos (inability to fully close eyes)
  • Cleft lip & palate
  • Atrial septal defect
  • Oligodontia
  • Absence of lymphedema

AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

The presence of lymphatic vessels on lymphoscintigraphy in LDS contrasts with other causes of primary lymphedema, including Milroy disease and Meige disease, which show aplasia or hypoplasia of the lymphatic vessels.

2.

Inheritance is said to be autosomal dominant; most affected individuals represent simplex cases (i.e., a single occurrence in a family) [Hoque et al 2007].

3.

Nail changes are different from the typically discolored nails often associated with chronic lymphedema.

4.

Distichiasis should also be clinically distinguished from trichiasis, a more common condition in which lashes arise normally from the anterior lamella of the eyelids but are misdirected. The misdirected lashes can cause symptoms similar to distichiasis (e.g., corneal irritation and photophobia).

From: Lymphedema-Distichiasis Syndrome

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