Clinical heterogeneity in lymphoedema-distichiasis withFOXC2 truncating mutations

BACKGROUND Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac...

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Bibliographic Details
Published in:Journal of medical genetics 2001-11, Vol.38 (11), p.761
Main Authors: Erickson, Robert P, Dagenais, Susan L, Caulder, Mark S, Downs, Catherine A, Herman, Gail, Jones, Marilyn C, Kerstjens-Frederikse, Wilhelmina S, Lidral, Andrew C, McDonald, Marie, Nelson, Christine C, Witte, Marlys, Glover, Thomas W
Format: Article
Language:English
Subjects:
Age
Birth defects
Cataracts
Children & youth
clinical heterogeneity
Congenital diseases
distichiasis
Edema
Families & family life
forkhead gene
Lymphatic system
Lymphedema
lymphoedema
Mutation
Puberty
Pulmonary arteries
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Summary:BACKGROUND Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac defects, cleft palate, and extradural cysts. Photophobia, exotropia, ptosis, congenital ectropion, and congenital cataracts are additional eye findings. Recently, we reported that truncating mutations in the forkhead transcription family member FOXC2resulted in LD in two families. METHODS The clinical findings in seven additional families with LD, including the original family described by Falls and Kertesz, were determined and mutational analyses were performed. RESULTS Distichiasis was the most common clinical feature followed by age dependent lymphoedema. There is a wide variation of associated secondary features including tetralogy of Fallot and cleft palate. The mutational analyses identified truncating mutations in all of the families studied (two nonsense, one deletion, three insertion, and one insertion-deletion), which most likely result in haploinsufficiency ofFOXC2. CONCLUSIONS FOXC2mutations are highly penetrant with variable expressivity which is not explicable by the pattern of mutations.
ISSN:0022-2593
1468-6244
DOI:10.1136/jmg.38.11.761