Microcephaly Chorioretinopathy Syndrome
Also referred to as: MLCRD Syndrome
Synonyms:
Heredity:
Diagnosis:
Symptoms:
Complications:
Treatment:
June 8, 2008
------------------------
LYMPHEDEMA, MICROCEPHALY, CHORIORETINOPATHY SYNDROME |
GeneTests, Links | |
LYMPHEDEMA, MICROCEPHALY, CHORIORETINOPATHY SYNDROME |
In 5 members of 4 generations of a Chinese family, Leung (1985) described the combination of microcephaly and lymphedema. The lymphedema was present at birth or began soon after birth. Intelligence was normal. Male-to-male transmission was observed. Crowe and Dickerman (1986) described congenital lymphedema in association with microcephaly in a young boy and his maternal uncle. The mother, maternal grandmother and a sister of the grandmother had microcephaly. The pattern was consistent with X-linkage but may have been indicative of autosomal recessive inheritance with reduced expression in females; the proband's mother, grandmother, and great aunt were microcephalic. In an accompanying editorial, Opitz (1986) made many useful comments. Congenital lymphedema is frequent and represents delay in the maturation of the lymphatics and delay in clearing of the lymphedema regularly present in the fetus. 'Lymphedema nails,' i.e., white nails, especially in the toes, is a persisting sign. Coarseness of the hair follicles over the dorsum of the hands and feet and first phalanges where edema was present earlier is another sign. Unusual persistence of fetal lymphedema is usually associated with congenital hypotonia which clears faster than the lymphedema. Lymphedema in the hands causes thick volar tissues and later numerous white lines seen on palm prints and with a magnifying glass. Change in the pattern of hair may be seen in other areas of the body in addition to the nape of the neck, e.g., in the forearms. Leung (1987) emphasized the intellectual normality in these cases.
Jarmas et al. (1981) described 2 brothers with severe microcephaly, microphthalmos, retinal folds, and visual deficit. Their mother was also microcephalic and showed mild mental retardation. Young et al. (1987) reported a retarded boy with microcephaly, microphthalmos, and retinal folds. His mother and sister showed microphthalmos and the sister was also microcephalic. Angle et al. (1994) pointed out that the patients of Jarmas et al. (1981) and Young et al. (1987) had lymphedema in addition to microcephaly and chorioretinal dysplasia.
Feingold and Bartoshesky (1992) described 2 unrelated boys with microcephaly, lymphedema, and chorioretinal dysplasia. They concluded that their patients had the same entity as the patients reported by Leung (1985), who had an autosomal dominant disorder, and those reported by McKusick et al. (1966), who had an autosomal recessive disorder (see 251270).
Angle et al. (1994) presented 2 unrelated boys with microcephaly, lymphedema, and chorioretinal dysplasia. Kozma et al. (1996) described a sister and brother from a nonconsanguineous Saudi family who, in addition to severe microcephaly (without mental retardation) and lymphedema, had attention deficit disorder. One brother was more severely affected, and X-linked dominant inheritance could not be excluded.
Strenge and Froster (1998) described a boy with congenital microcephaly and lymphedema. He also had short stature, a feature that had not been described as part of this syndrome, even though it was present in 1 patient reported by Fryns et al. (1995). Bilateral limb lymphedema with lymphedema toenails was still present at age 2 years. At the age of 4 years, the lymphedema began decreasing. At the age of 8 years, lymphedema was restricted to the surface of the toes and the distal part of both feet. His height was at the 3rd centile; the occipital-frontal circumference was 48 cm (less than 3rd centile). Psychomotor development was normal.
Limwongse et al. (1999) provided follow-up on the family reported by Crowe and Dickerman (1986) which was considered to have the microcephaly-lymphedema syndrome. They found chorioretinal dysplasia with variable visual deficit in multiple relatives, supporting the concept that the combination of microcephaly, lymphedema, and chorioretinopathy constitutes a single autosomal dominant genetic entity with variable expression. In an editorial comment on the report by Crowe and Dickerman (1986), Opitz (1986) had suggested that the facial characteristics of their proband at birth and during childhood resembled those of other patients with disorders associated with congenital lymphedema, i.e., what Opitz (1986) called the 'congenital lymphedema facies' (thick tissues, full cheeks, underdeveloped bridge of nose and supraorbital ridges, thick epicanthal folds, bilateral ptosis with thick lids, and micrognathia). Limwongse et al. (1999) noted a striking similarity between the facial characteristics of their proband at age 14 years and those of the 11-year-old patient of Sadler and Robinson (1993) with microcephaly and chorioretinopathy (see 156590). Both patients had prominent ears, broad nasal bridge, broad and large nasal tip with anteverted nares, prominent full lips, and pointed chin.
Abdel-Salam et al. (2000) stated that 40 cases of microcephaly with chorioretinopathy, some with additional features such as lymphedema, had been reported. They noted that the facial features in their 2 patients, who had the additional features of severe mental retardation, epilepsy, and spasticity (see 251270), were similar to those described by Limwongse et al. (1999).
Vasudevan et al. (2005) reported 3 unrelated male patients with all of the major features of the microcephaly, lymphedema, chorioretinal dysplasia syndrome. All had a distinct facial appearance involving upslanting palpebral fissures, broad nose with rounded tip, anteverted nares, long philtrum with thin upper lip, pointed chin, and prominent ears. Vasudevan et al. (2005) stated that these cases support the hypothesis of a characteristic facial phenotype in MLCRD syndrome.
Marla J. F.
O'Neill - updated : 12/11/2006
Victor A. McKusick - updated : 2/10/2000
Victor A. McKusick - updated : 1/15/1999
Iosif W. Lurie - updated : 7/26/1996
Victor A. McKusick : 6/2/1986
carol : 12/14/2006
------------------------
Hospital Universitario La Paz, Pediatric Ophthalmology , Madrid , Spain.
Background: Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a rare malformative inherited disorder that can be associated with other systemic features. Other ocular and brain anomalies rather than microcephaly and chorioretinal dysplasia have been inconstantly reported in this syndrome. Methods: We present a case of microcephaly-lymphedema-chorioretinal dysplasia with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia, posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve aplasia, persistent fetal vasculature, and absent retinal vessels. Results: Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis cerebelosum and confirmed optic nerve hypoplasia. Conclusions: The developmental alterations observed in the retina of this patient could be analogous to central nervous system anomalies, reflecting a reduction in neural population. Ophthalmic examination of children with microcephaly is warranted.
PubMed
------------------------
Medical Genetics Unit, Biomedical Sciences, St. George's University of London, London SW17 0RE, UK.
We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. Subsequent Sanger sequencing of KIF11 in a further 15 unrelated microcephalic probands with lymphedema and/or chorioretinopathy identified additional heterozygous mutations in 12 of them. KIF11 encodes EG5, a homotetramer kinesin motor. The variety of mutations we have found (two nonsense, two splice site, four missense, and six indels causing frameshifts) are all predicted to have an impact on protein function. EG5 has previously been shown to play a role in spindle assembly and function, and these findings highlight the critical role of proteins necessary for spindle formation in CNS development. Moreover, identification of KIF11 mutations in patients with chorioretinopathy and lymphedema suggests that EG5 is involved in the development and maintenance of retinal and lymphatic structures.
SciVerse
http://www.sciencedirect.com/science/article/pii/S0002929711005532
------------------------
------------------------
Microcephaly with chorioretinopathy in a brother-sister pair: evidence for germ line mosaicism and further delineation of the ocular phenotype.
Am J Med Genet A. 2007 Jun
Casey Eye Institute and Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon 97239, USA. trzupekk@ohsu.edu
Microcephaly with chorioretinopathy (OMIM 156590) is an autosomal dominant syndrome, characterized primarily by chorioretinal lesions and microcephaly. The phenotype is variable, and has been described in association with retinal dysplasia that can be stable or show progressive degeneration, retinal folds, lymphedema, and mental retardation. We describe two siblings with microcephaly, mental retardation, and variable retinal and choroidal abnormalities. Patient 1 has multiple atrophic and dysplastic-appearing lesions of the retina and choroid in each eye. An ERG at 5 months of age disclosed markedly subnormal scotopic and photopic responses with delayed flicker timing. Patient 2 has bilateral macular folds with vitreoretinopathy, serous retinal detachments, glaucoma, and cataracts OU. Both have mental retardation with hypotonia and severe microcephaly. Chorioretinopathy and retinal folds have been described independently in microcephaly with chorioretinopathy. The present sibs are the first in whom these features are observed while the parents are normal. Our findings support an expansion of the ocular phenotype and suggest the existence of germ line mosaicism.
===========================
External Links:
---------------
LYMPHEDEMA, MICROCEPHALY, CHORIORETINOPATHY SYNDROME
http://bjo.bmjjournals.com/cgi/content/full/85/4/496d
..........
http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.31717/abstract
===========================
Join us as we work for lymphedema patients everywhere:
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/phpBB3/viewforum.php?f=3
For information aboutow 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
Lipedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lipedema
Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
Lymphedema and
Pain Management
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pain_management
Manual
Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)
Infections
Associated with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
How to Treat a
Lymphedema Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
Fungal
Infections Associated with Lymphe
http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema
Lymphedema in
Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphoscintigraphy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphoscintigraphy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Extraperitoneal
para-aortic lymph node dissection (EPLND)
Axillary
node biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=axillary_node_biopsy
Sentinel Node
Biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy
Small
Needle Biopsy - Fine Needle Aspiration
http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Lymphedema
Gene FOXC2
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2
Lymphedema Gene VEGFC
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc
Lymphedema Gene SOX18
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18
Lymphedema
and Pregnancy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy
Home page: Lymphedema People
http://www.lymphedemapeople.com
Page Updated: Jan. 5, 2012