Lymphedema Distichiasis
Lymphedema distichiasis is commonly referred to as the "double row of eye lashes" expression of hereditary lymphedema. The gene FOXC2 mututation is involved with this symptom.
Cause: Mutation of FOXC2
Distichiasis-Lymphedema Syndrome is a rare inherited disorder characterized by the presence of extra eyelashes (distichiasis) and swelling of the arms and legs (lymphedema). Swelling of the legs, especially below the knees, and eye irritation are common in people with this disorder. Occasionally, cysts on the spine (epidural) and other abnormalities of the spinal column may also occur. Distichiasis-Lymphedema Syndrome is inherited as an autosomal dominant genetic trait. (1)
LYMPHEDEMA-DISTICHIASIS
SYNDROME
Gene Map Locus:
16q24.3
Genetics:
Mutation in the forkhead family transcription factor gene MFH1
(FOX2; 602402). Related disorders with overlapping features include
hereditary
lymphedema II. (Meige
Syndrome); lymphedema with
ptosis and lymphedema with
yellow
nail syndrome.
Description:
Expressed as the characteristic "double-row" of
eye lashes. Usually not detected or observed until a compilcation such
as
corneal irritation or ulceration brings it to the attention of the
patient or
physician.
Related genetic features (lymphedema):
Cardiac defects, cleft-palate,
spinal extradural cysts and photofobia.
-----------------------------------
Lymphedema distichiasis
G. Brice and A. Child
Department of Cardiological Science
St. Georges Hospital Medical School, London
The features of this condition are lymphedema of pubertal onset,
preceded by the
development of extra lashes arising from the meibomian gland openings.
These can
vary from a full extra set of lashes to the odd extra lash. They are
normally
soft and pale but often cause corneal irritation. Cases of apparently
severe
distichiasis in which patients have been unaware of the extra lashes
have been
reported (Kremer et al. 1986, Mangion et al. 1999) underlining the need
for
ocular examination in all patients in which there is a family history
of
distichiasis or lymphedema. Equally, patients referred with
distichiasis alone
should be examined for limb swelling and a family history sought. In
our series
of 10 families ascertained via an ophthalmic department there are no
families
with distichiasis alone. In most cases the extra lashes are clearly
visible and
slit lamp examination is not required to confirm the diagnosis.
Treatment is by
epilation, cryotherapy or lid splitting surgery (Shammas et al. 1979,
Temple
& Collin 1994).
Lymphedema distichiasis is typically associated with the uncommon
lymphangiographic finding of hyperplasia, in which there are numerous
dilated
lymphatic vessels in the legs (Dale 1987). In addition it is often
associated
with other congenital abnormalities such as heart defects, cleft
palate, ptosis
and vertebral anomalies (Temple & Collin 1994).
Mangion et al. (1999) published linkage to chromosome 16q24.3 in three
families
with lymphedema distichiasis. The addition of further individuals from
the
largest of three families subsequently reduced the critical interval
from 16cM
to 2Mb. Eight further lymphoedema-distichiasis families were also
consistent
with linkage to the same 2Mb region (Bell et al. 2000). Recently, the
FOXC2
(MFH-1) transcription factor gene was found to harbour mutations in
families
affected by lymphedema distichiasis. One nonsense mutation and one four
base
paid duplication were found in unrelated patients (Fang et al. 2000).
Subsequently, our group has located 14 FOXC2 mutations in distichiasis
families,
13 of which were insertions or deletions. Mutation sites are scattered
throughout the gene but no apparent genotype-phenotype correlation was
evident
(Bell et al., submitted for publication). Further work will be carried
out to
determine the effect of the mutations on protein function.
Acknowldgement
UK Lymph.com
http://www.uklymph.com/latest_news/ln_inheritance_of_primary_lymphedema.php
-----------------------------------
| LYMPHEDEMA-DISTICHIASIS SYNDROME |
Alternative titles; symbols
LYMPHEDEMA WITH DISTICHIASIS Gene map locus 16q24.3A number sign
(#) is used with this entry because of evidence that the
lymphedema-distichiasis syndrome is caused by mutation in the forkhead
family
transcription factor gene MFH1 (FOXC2; 602402).
Allelic disorders with overlapping features include hereditary
lymphedema type
II, or Meige syndrome (153200),
lymphedema and ptosis (153000),
and lymphedema and yellow nail syndrome (153300).
Lymphedema-distichiasis
is an autosomal dominant disorder that classically
presents as lymphedema of the limbs and double rows of eyelashes
(distichiasis).
Irritation of the cornea, with corneal ulceration in some cases, brings
the
patients to the attention of ophthalmologists. Other complications may
include
cardiac defects, cleft palate, spinal extradural cysts, and photophobia
(Fang
et al., 2000).
The first
description of the combination of lymphedema and distichiasis was
reported by Neel
and Schull (1954). Falls
and Kertesz (1964) reported 4 sibs with bilateral lymphedema
of the legs and
distichiasis. One of the 4 had striking webbed neck, whereas 2 were
thought to
have mild webbing. Several of the affected persons complained of
photophobia and
had partial ectropion of the lateral third of the lower lids, giving
them a
wide-eyed appearance. The father and one of his brothers reportedly had
lymphedema, distichiasis, and webbed neck, and the paternal grandmother
had
lymphedema. An affected paternal uncle died of metastatic fibrosarcoma
originating in an edematous leg.
Chynn
(1967)
saw these features in combination with spinal extradural cyst (271100)
in 2, and perhaps 3, black sibs. Spinal changes were present but
asymptomatic in
the affected father, daughter, and son described by Robinow
et al. (1970). Hoover
(1971) studied a family with the lymphedema-distichiasis
syndrome in 3
generations.
Dale
(1987)
noted that 'bilateral hypoplasia' lymphedema is an uncommon form of
lymphedema
in which lymphography shows abundant, dilated lymphatics occurring in
both lower
limbs, and the thoracic duct is either absent, obstructed, or deformed.
Further,
he noted that this form of lymphedema is often associated with other
congenital
malformations, including distichiasis and congenital heart disease. In
a survey
of 725 patients with primary lymphedema treated at St. Thomas'
Hospital, Dale
(1987) found 5 with distichiasis, all of whom showed
bilateral hyperplasia.
Of 475 patients investigated by lymphography, only 30 (6%) had
bilateral
hyperplasia. Of these, 11 (36%) had a positive family history, and 3
had both
distichiasis and bilateral hyperplasia. Further examination of these
affected
families showed a variable phenotype, in that some members had both
lymphedema
and distichiasis, whereas others had only lymphedema. Kolin
et al. (1991) described 2 cases of distichiasis, one in
association with
familial and congenital lymphedema with hypoplasia of lymphatics
(suggesting
Milroy disease), and the second in association with pubertal onset of
lymphedema.
Johnson
et
al. (1999) described this syndrome in a 14-year-old African
American girl
who presented with a 3-month history of nonpitting edema beginning on
the left
distal leg and progressing to both lower extremities and extending to
the thigh.
She had had surgery for dual-chamber pacemaker placement for
symptomatic
bradycardia due to Mobitz type I secondary atrioventricular block and
correction
of supracardiac total anomalous pulmonary venous connection and patent
ductus
arteriosus (see 607411).
The family history was notable for a maternal grandmother and a
great-grandmother with lymphedema and congenital heart disease; the
medical
condition of the mother of the proband was unknown. Ophthalmic
examination
showed a bilateral double row of eyelashes without corneal abrasion.
Brice
et al.
(2002) described in detail the clinical findings in 74
affected subjects
from 18 families, as well as 6 isolated cases, with the
lymphedema-distichiasis
syndrome. All patients had mutations in the FOXC2 gene, except 2
affected
brothers who showed linkage to the FOXC2 gene. Fifty-seven of the 74
patients
had clinical evidence of lymphedema, with the onset in males (9 to 11
years)
significantly earlier than the onset in females (14 to 20 years), but
penetrance
appeared complete in both sexes by the age of 40 years. The lymphedema
was
usually bilateral and asymmetric. Lymphoscintigram in 9 patients showed
abnormally low uptake of radioactive colloid in inguinal nodes,
increased number
of lymph conducting pathways, and lymph reflux. Distichiasis occurred
in 94% of
patients, 74% of whom had complications, including corneal irritation,
photophobia, conjunctivitis, and styes. Ptosis was noted in 31%,
congenital
heart disease in 6.8%, and cleft palate in 4%. No patients had spinal
extradural
cysts. Varicose veins, present in 49%, were notable for early onset and
increased prevalence compared to the general population, and Brice
et al. (2002) emphasized the link between the lymphatic and
vascular systems
being affected. There were no apparent genotype/phenotype correlations.
In 3 families with lymphedema-distichiasis, Mangion et al. (1999) found linkage to 16q24.3. Subsequent analysis of the region for recombinants placed the locus between D16S422 and D16S3074, a distance of approximately 16 cM.
Erickson
et
al. (1995) described neonatal lymphedema, similar to that
seen in Turner
syndrome, associated with a Y;16 translocation in a male infant. They
were not
able to find a candidate gene on the Y chromosome to account for the
lymphedema
and turned their attention to the breakpoint in chromosome 16 at
16q24.3. When
the lymphedema-distichiasis syndrome was mapped to a 16-cM region on
distal
chromosome 16, they determined that the breakpoint in the Y;16
translocation was
within this region and narrowed the region to a 20-kb segment.
In 2 families with autosomal dominant lymphedema-distichiasis syndrome, Fang et al. (2000) identified inactivating mutations in the FOXC2 gene: a nonsense mutation (602402.0001) and a frameshift mutation (602402.0002),
Erickson et al. (2001) described truncating mutations in the FOXC2 gene in 9 families with lymphedema-distichiasis syndrome, 6 of which had not previously been reported.
Corbett et al. (1982); Pap et al. (1980); Schwartz et al. (1980)
Cassandra L.
Kniffin - reorganized : 11/19/2003
Cassandra L. Kniffin - updated : 11/12/2003
Michael J. Wright - updated : 10/22/2002
Victor A. McKusick - updated : 12/12/2000
Victor A. McKusick - updated : 1/11/2000
Victor A. McKusick - updated : 6/3/1999
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=153400
-------------------------------------
|
Authors:
|
Sahar Mansour, FRCP
Glen W Brice, RGN BSc (Hons) Steve Jeffery, PhD Peter Mortimer, MD, FRCP |
| Last
Update: 2 August 2007 |
|
|
Initial Posting: |
|
Disease characteristics. Lymphedema-distichiasis syndrome is characterized by lower-limb lymphedema and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins, congenital heart disease, and ptosis. About 25% of individuals are asymptomatic.
Diagnosis/testing. The diagnosis of lymphedema-distichiasis syndrome is made clinically and is based on the presence of primary lymphedema and distichiasis. FOXC2 is the only gene known to be associated with lymphedema-distichiasis syndrome. Molecular genetic testing of the FOXC2 gene is clinically available.
Management. Treatment of manifestations: lubrication, plucking, cryotherapy, electrolysis, or lid splitting for treatment of distichiasis; fitted stockings and bandages to improve swelling and discomfort associated with edema. Prevention of secondary complications: To prevent secondary cellulitis treat athlete's foot and other infections promptly; treat early cellulitis with antibiotics. Other: Diuretics are not effective in the treatment of lymphedema.
Genetic counseling. Lymphedema-distichiasis syndrome is inherited in an autosomal dominant manner. Approximately 75% of affected individuals have an affected parent; about 25% have de novo mutations. Each child of an individual with lymphedema-distichiasis syndrome has a 50% chance of inheriting the mutation. Disease severity cannot be predicted and is variable even within the same family. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in an affected family member; however, it is rarely requested. Fetal echocardiography is recommended because of the increased risk of congenital heart disease.
The clinical diagnosis of lymphedema-distichiasis syndrome is based on the presence of the following:
Primary lymphedema (chronic swelling of the extremities caused by an intrinsic dysfunction of the lymphatic vessels)
Distichiasis (aberrant, extra eyelashes arising from the meibomian glands)
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information. —ED.
Gene. FOXC2 is the only gene known to be associated with lymphedema-distichiasis syndrome [ Fang et al 2000].
Other loci. Four affected families with no mutation identified in FOXC2 have been reported. Brice et al ( 2002) reported one family out of 18 families and six simplex cases (i.e., single occurrences of lymphedema-distichiasis syndrome in a family) in whom linkage was compatible with the FOXC2 locus but no mutation was identified. Finegold et al ( 2001) reported three small families out of 14 with no identifiable mutation; however, no linkage data were available.
Clinical testing
Sequence analysis of the entire coding region detects mutations in about 95% of individuals with lymphedema-distichiasis syndrome. Over 90% of mutations are small deletions or insertions. Four possible missense mutations (one of which has uncertain pathogenesis) and a small number of nonsense mutations have been reported. No entire gene deletions have been reported.
Research testing. For those in whom no mutation is detected in the coding region by sequence analysis, the 5' and 3' regions of the FOXC2 gene can be sequenced and analyzed. Detection rate for coding region mutations should be 100%, other than laboratory error.
The most common findings in lymphedema-distichiasis syndrome are lower-limb lymphedema and distichiasis.
Lymphedema. Lymphedema is present in most individuals with lymphedema-distichiasis syndrome. It typically appears in late childhood or puberty (age range 7-40 years) [ Erickson et al 2001 , Brice et al 2002], although congenital onset has been reported [ Finegold et al 2001 ; Brice, unpublished observations].
Lymphedema is confined to the lower limbs, is often asymmetric, and can be unilateral. The severity of the lymphedema varies within families. Males develop edema at a significantly earlier age and have more problems with cellulitis than females. Sixty-five percent of males in one series complained of recurrent cellulitis in the edematous leg, compared to 25% of females [ Brice et al 2002].
Primary lymphedema is usually associated with hypoplasia or aplasia of the lymphatic vessels. However, individuals with lymphedema-distichiasis syndrome have an increased number of lymphatic vessels and inguinal lymph nodes [ Dale 1987 , Brice 2003]. Although present, the lymphatic vessels do not appear to function properly.
Isotope lymphoscintigraphy can be used to demonstrate that the swelling is caused by lymphedema. Radioactive colloid is injected into the toe web spaces and uptake in the ilioinguinal nodes is measured at intervals. Low uptake can be demonstrated in most affected individuals in association with dermal backflow, indicating lymph reflux into the lower limbs. This technique replaces lymphangiography (x-ray after injection of dye into the lymphatic vessels in the foot).
Distichiasis. Distichiasis describes the presence of aberrant eyelashes arising from the meibomian glands on the inner aspects of the inferior and superior eyelids. These range from a full set of extra eyelashes to a single hair. Distichiasis is observed in 94% of individuals with lymphedema-distichiasis syndrome [ Brice et al 2002]. Although distichiasis may be present at birth, it may not be recognized until early childhood.
About 75% of affected individuals have ocular problems related to distichiasis including corneal irritation, recurrent conjunctivitis, and photophobia. About 25% of individuals have no symptoms from distichiasis and are thus not aware of it. Therefore, any individual with primary lymphedema of the lower limbs should be examined carefully for the presence of distichiasis.
Finegold et al ( 2001) described one family with a FOXC2 mutation with lymphedema only; however, only three individuals were affected and no comment was made as to whether they were examined by slit lamp for evidence of distichiasis. Sometimes the distichiasis can be very subtle. In a study of 23 probands reported to have Meige disease (see Differential Diagnosis) only one was found to have a mutation in FOXC2. More extensive examination of the individuals in this family revealed that although the proband did not have distichiasis, four affected relatives had evidence of distichiasis on slit-lamp examination [Rezaie et al, personal communication].
In one family described distichiasis was associated with a mutation in FOXC2 but none of the affected individuals had evidence of lymphedema. However, the two affected individuals in the family were the 13-year-old proband (who could still develop lymphedema) and her father [ Brooks et al 2003].
Varicose veins. The incidenceof varicose veins is much higher, and onset earlier, in individuals with lymphedema-distichiasis syndrome than in the general population. About 50% of individuals with lymphedema-distichiasis syndrome have varicose veins [ Brice et al 2002]. In one family, light-reflective rheography and Doppler studies showed bilateral incompetence at the sapheno-femoral junction and long saphenous vein, which were presumed to be congenital abnormalities affecting both deep and superficial veins [ Rosbotham et al 2000]. Ongoing studies of venous abnormalities suggest that they are present in all individuals with FOXC2 mutations [ Mellor et al 2007].
Ptosis. Approximately 30% of individuals with lymphedema-distichiasis syndrome have unilateral or bilateral congenital ptosis of variable severity.
Congenital heart disease. Congenital heart disease occurs in 7% of individuals with lymphedema-distichiasis syndrome. Structural abnormalities include ventricular septal defect, atrial septal defect, patent ductus arteriosis, and tetralogy of Fallot. Cardiac arrhythmia, most commonly sinus bradycardia, may also occur.
Cleft palate. About 4% of individuals have cleft palate with or without Pierre-Robin sequence.
Other findings. Other abnormalities include scoliosis, spinal extradural cysts [ Kanaan et al 2006], neck webbing, uterine and renal anomalies, strabismus, and synophrys. Neonatal chylothorax has been reported in one case only in association with congenital heart disease [ Chen et al 1996]. One paper suggested an association with yellow nails, but discolored nails are often a feature of chronic lymphedema regardless of cause.
No genotype-phenotype correlation for the major clinical signs has been reported; however, a preliminary study suggested that asymptomatic anomalies of the anterior chamber of the eye are more extensive if the mutation is in the forkhead domain rather than in other regions of the gene [ Lehmann et al 2003].
Approximately 80% of individuals with lymphedema-distichiasis syndrome have lymphedema by early adulthood (age 30 years), although a few individuals may develop lymphedema later.
About 94% of affected individuals have distichiasis. In all families reported with mutations in FOXC2, at least one individual has had distichiasis.
No evidence of anticipation has been reported.
Lymphedema and ptosis, described as a separate entity in OMIM (153000), is thought to be the same as lymphedema-distichiasis syndrome [ Finegold et al 2001].
The prevalence of lymphedema-distichiasis syndrome is not known; however, it is a well-recognized cause of autosomal dominant primary lymphedema.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Lymphedema. The presence of lymphatic vessels in lymphedema-distichiasis syndrome contrasts with other causes of primary lymphedema such as Milroy disease and Meige disease, which show aplasia or hypoplasia of the lymphatic vessels.
Meige disease presents with primary lymphedema at puberty. Distichiasis is not observed. Meige disease predominantly affects women, but inheritance is autosomal dominant. The causative gene(s) has/have not yet been confirmed.
Hypotrichosis-lymphedema-telangiectasia syndrome is the association of childhood-onset lymphedema in the lower limbs, loss of hair, and telangiectasia, particularly in the palms. Inheritance is either autosomal dominant or autosomal recessive. Mutations in SOX18 are causative [ Irrthum et al 2003].
Lymphedema with yellow nails (yellow nail syndrome, YNS) often presents after age 50 years. The nails in YNS are very slow growing, with transverse over-curvature and hardening of the nail plate. The nail changes are different from the typically discolored nails that are often associated with chronic lymphedema. Inheritance is said to be autosomal dominant; however, most cases are simplex (i.e., a single occurrence in a family) [ Hoque et al 2007].
Distichiasis
Blepharocheilodontic syndrome is the association of lagophthalmos (inability to fully close eyes), cleft lip and palate, atrial septal defect, and oligodontia. Distichiasis is a feature; lymphedema is not observed.
To establish the extent of disease in an individual diagnosed with lymphedema-distichiasis syndrome, the following evaluations are recommended:
Referral to an ophthalmologist (preferably one familiar with distichiasis) for slit-lamp examination, as the extra lashes may be subtle and easily missed on clinical examination
Physical examination to document the presence of manifestations and identify evidence of cellulitis
Isotope lymphoscintigraphy to confirm underlying abnormality of the lymphatics as the cause of the edema
Physical examination of the heart and possible echocardiography if murmur or arrhythmia is identified
Conservative management of symptomatic distichiasis with lubrication or epilation (plucking), or more definitive management with cryotherapy, electrolysis, or lid splitting [ O'Donnell & Collin 1993]. Recurrence is possible even with more definitive treatment.
Referral to a lymphedema therapist regarding management of edema (fitting stockings, massage). Although the edema cannot be cured, some improvement may be possible with the use of carefully fitted stockings and/or bandaging, which may reduce the size of the swelling as well as the discomfort associated with it.
Surgery for ptosis if clinically indicated (e.g., obscured vision, cosmetic appearance)
Referral to neurosurgery for individuals with symptomatic spinal cysts (i.e., any neurologic signs or symptoms especially in the lower limbs)
Conservative management of varicose veins if possible, as surgery could aggravate the edema and increase the risk of infection or cellulitis
Standard treatment for scoliosis
Prevention of secondary cellulitis in areas with lymphedema, particularly as cellulitis may aggravate the degree of edema. Prophylactic antibiotics (e.g., penicillin V 500 mg daily) are recommended for recurrent cellulitis.
Prompt treatment of early cellulitis with appropriate antibiotics (See the British Lymphology Society Consensus Statement for information on appropriate antibiotics.) It may be necessary to give the first few doses intravenously if there is severe systemic upset.
Prevention of foot infections, particularly athlete's foot/infected eczema by treatment with appropriate creams/ointments
Diuretics are not effective in the treatment of lymphedema.
Cosmetic surgery is often associated with disappointing results.
Genetics clinics are a source of information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
Support groups have been established for individuals and families to provide information, support, and contact with other affected individuals. The Resources section may include disease-specific and/or umbrella support organizations.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory. —ED.
Lymphedema-distichiasis syndrome is inherited in an autosomal dominant manner.
Parents of a proband
Note: Although most individuals diagnosed with lymphedema-distichiasis syndrome have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members as a result of the variable expressivity.
Sibs of a proband
Offspring of a proband. Each child of an individual with lymphedema-distichiasis syndrome has a 50% chance of inheriting the mutation. Disease severity cannot be accurately predicted and is variable even within the same family.
Other family members of a proband. The risk to other family members depends upon the genetic status of the proband's parents. If a parent is found to be affected, his or her family members are at risk.
It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.
Considerations in families with an apparent de novo mutation. When neither parent of a proband with an autosomal dominant condition has the disease-causing mutation or clinical evidence of the disorder, it is likely that the proband has a de novo mutation. However, possible non-medical explanations including alternate paternity or undisclosed adoption could also be explored.
Family planning. The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
DNA banking. DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%. See DNA Banking for a list of laboratories offering this service.
Molecular genetic testing. Prenatal diagnosis for pregnancies at increased risk is possible in the US (availability may vary by country) by analysis of DNA extracted from fetal cells obtained by chorionic villus sampling (CVS) at about ten to 12 weeks' gestation or amniocentesis usually performed at about 15-18 weeks' gestation. The disease-causing mutation of an affected family member must be identified before prenatal testing can be performed. Although available, prenatal diagnosis for lymphedema-distichiasis syndrome is rarely requested.
|
Gene Symbol
|
Chromosomal Locus
|
Protein Name
|
|
FOXC2
|
16q24.3
|
Forkhead box protein C2
|
|
Gene Symbol
|
Entrez Gene
|
HGMD
|
GeneCards
|
GDB
|
GenAtlas
|
|
FOXC2
|
Normal allelic variants: The FOXC2 gene is composed of a 1.5-kb single exon. SNPs reported in the 5' region of the gene include -512C>T [ Ridderstrale et al 2002] and -350G>T [ Osawa et al 2003], and in the 3' region, 1548C>T and 1702C>T [ Kovacs et al 2003]. 1761G>A has been identified [ Sholto-Douglas-Vernon et al 2005].
Pathologic
allelic variants:
Information on at least 35 different insertions and deletions situated throughout
the gene has been published to date.
The region 900-920 bp appears to be a "hot spot"
for mutations, possibly because of
the presence of a repeated GCCGCCGC element [Jeffery, unpublished
data]. Several nonsense mutations have
been reported, as well as four missense mutations: p.Ser125Leu [
Bell et al
2001], p.Arg121His [ Brice et al 2002],
p.Trp116Ala, and p.Ser235Ile [ Sholto-Douglas-Vernon
et al 2005]. The first three are presumed to be causative;
the status of p.Ser235Ile is unknown.
Mutations in FOXC1
give rise to Axenfeld-Rieger anomaly and congenital glaucoma. Mutations analogous to
p.Ser125Leu and p.Arg121His in FOXC2
have been shown to inactivate FOXC1
[ Saleem et al 2003].
Normal gene product: Because the gene has no introns, no isomers exist. The normal product is active as a transcriptional regulator during embryonic development and is also expressed in white adipose tissue in adults and in human adult lymphatics [ Petrova et al 2004].
Abnormal gene product: The assumed method of pathogenesis is haploinsufficiency. It is not clear whether the frameshift mutations produce a protein product with novel amino acids or whether the mRNA or proteins are degraded.
http://www.genetests.org/profiles/lds/index.html
-------------------------------------
External Links
----------
Spinal extradural arachnoid cysts associated with distichiasis and lymphedema
Am J Med Genet A. 2007 Apr
Wiley InterScience
http://www3.interscience.wiley.com/journal/114186535/abstract?CRETRY=1&SRETRY=0
...............
Lymphoedema-distichiasis and FOXC2: unreported mutations, de novo mutation estimate, families without coding mutations.
Hum Genet. 2005 Jul
Springer Link
http://www.springerlink.com/content/w37386751610nw14/
...............
Lymphedema
distichiasis(1)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10417285&dopt=Abstract
...............
Lymphedema distichiasis syndrome and FOXC2 gene mutation
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12383817&dopt=Abstract
...............
Distichiasis
Author: Soheila Rostami, MD, Oculoplastic Fellow, Clinical Instructor,
Department of Ophthalmology, University of Maryland
Soheila Rostami, MD, is a member of the following medical societies:
American
Academy of Ophthalmology, and American Medical Association
http://www.emedicine.com/oph/topic603.htm
===========================
Join us as we work for lymphedema patients everywehere:
Advocates for Lymphedema
Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.
http://health.groups.yahoo.com/group/AdvocatesforLymphedema/
| Subscribe: | AdvocatesforLymphedema-subscribe@yahoogroups.com |
Pat O'Connor
Lymphedema People / Advocates for Lymphedema
===========================
For information about Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema\
For Information about Lymphedema Complications
http://www.lymphedemapeople.com/wiki/doku.php?id=complications_of_lymphedema
For Lymphedema Personal Stories
http://www.lymphedemapeople.com/phpBB2/viewforum.php?f=3
For information about How to Treat a Lymphedema Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
For information about Lymphedema Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
For information about Exercises for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
For information on Infections Associated with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
For information on Lymphedema in Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphedema Glossary
http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing
===========================
Lymphedema People - Support Groups
-----------------------------------------------
Children with Lymphedema
The time has come for families, parents, caregivers to have a support
group of their own. Support group for parents, families and caregivers
of chilren with lymphedema. Sharing information on coping, diagnosis,
treatment and prognosis. Sponsored by Lymphedema People.
http://health.groups.yahoo.com/group/childrenwithlymphedema/
Subscribe: childrenwithlymphedema-subscribe@yahoogroups.com
......................
Lipedema
Lipodema Lipoedema
No matter how you spell it, this is another very little understood and
totally frustrating conditions out there. This will be a support group
for those suffering with lipedema/lipodema. A place for information,
sharing experiences, exploring treatment options and coping.
Come join, be a part of the family!
http://health.groups.yahoo.com/group/lipedema_lipodema_lipoedema/?yguid=209645515
Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com
......................
MEN WITH LYMPHEDEMA
If you are a man with lymphedema; a man with
a loved one with lymphedema who you are trying to help and understand
come join us and discover what it is to be the master instead of the
sufferer of lymphedema.
http://health.groups.yahoo.com/group/menwithlymphedema/
Subscribe: menwithlymphedema-subscribe@yahoogroups.com
......................
All About Lymphangiectasia
Support group for parents, patients, children who suffer from all forms
of lymphangiectasia. This condition is caused by dilation of the
lymphatics. It can affect the intestinal tract, lungs and other
critical body areas.
http://health.groups.yahoo.com/group/allaboutlymphangiectasia/
Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com
......................
Lymphatic
Disorders Support Group @ Yahoo Groups
While we have a number of support groups for lymphedema... there is
nothing out there for other lymphatic disorders. Because we have one of
the most comprehensive information sites on all lymphatic disorders, I
thought perhaps, it is time that one be offered.
DISCRIPTION
Information and support for rare and unusual disorders affecting the
lymph system. Includes lymphangiomas, lymphatic malformations,
telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of
information available through sister site Lymphedema People.
http://health.groups.yahoo.com/group/lymphaticdisorders/
Subscribe: lymphaticdisorders-subscribe@yahoogroups.com
......................
All About Lymphedema
For our Google fans, we have just created this online support group in
Google Groups:
Homepage: http://groups-beta.google.com/group/All-About-Lymphedema
Group email: All-About-Lymphedema@googlegroups.com
......................
Lymphedema Friends
http://groups.aol.com/lymphedemafriend
If you an AOL fan and looking for a
support group in AOL Groups, come and join us there.
===========================
Lymphedema People New Wiki Pages
Have
you seen our new “Wiki” pages yet?
Listed below are just a sample of the more than 140 pages
now listed in our Wiki section. We are also working on hundred more. Come and take a
stroll!
Lymphedema Glossary
http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema
Arm
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=arm_lymphedema
Leg
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=leg_lymphedema
Acute
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=acute_lymphedema
The
Lymphedema Diet
http://www.lymphedemapeople.com/wiki/doku.php?id=the_lymphedema_diet
Exercises
for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
Diuretics
are not for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema
Lymphedema
People Online Support Groups
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_people_online_support_groups