Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hennekam syndrome is a rare, recently described genetic disorder in which facial anomalies and mental retardation accompany congenital lymphedema and intestinal lymphangiectasia. Several other somatic abnormalities have variously been described, as have milder degrees of lymphatic dysfunction. The authors herein describe a case of Hennekam syndrome in which the diagnostic difficulties were partially overcome by the judicious use of radionuclide scintigraphy to verify the lymphedematous component of the patient's presentation.
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PMID:Lymphoscintigraphic manifestations of Hennekam syndrome--a case report. 1060 68

We report two brothers with mental retardation, lymphoedema of the limbs and facial anomalies. Hennekam et al. (Am J Med Genet 34:593-600; 1989) described four patients with identical signs and intestinal lymphangiectasia. To confirm the diagnosis of Hennekam syndrome we undertook a duodenal biopsy from the older brother which revealed intestinal lymphangiectasia. So far only one patient with Hennekam syndrome and cerebral abnormalities has been described. This patient presented with pachygyria in the parietal area. Cerebral MRI in our two cases revealed small subcortical hyperintensities in both patients and a large cystic lesion in the younger patient probably representing an old media infarction.
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PMID:Two brothers with Hennekam syndrome and cerebral abnormalities. 1064 92

A 10-year-old girl with facial anomalies, mental retardation, peripheral lymphoedema, convulsions, cerebral cortical dysgenetic changes, bronchiectasis and chronic sinusitis is presented. She had features of both yellow nail syndrome and Hennekam syndrome. We think that our case might be a new congenital lymphoedema syndrome or an intermediate form between these syndromes.
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PMID:Congenital lymphoedema, bronchiectasis and seizure: case report. 1866 89

Lymphedema, lymphangiectasias, mental retardation and unusual facial characteristics define the autosomal recessive Hennekam syndrome. Homozygosity mapping identified a critical chromosomal region containing CCBE1, the human ortholog of a gene essential for lymphangiogenesis in zebrafish. Homozygous and compound heterozygous mutations in seven subjects paired with functional analysis in a zebrafish model identify CCBE1 as one of few genes causing primary generalized lymph-vessel dysplasia in humans.
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PMID:Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. 1993 64

Hennekam syndrome is a rare autosomal recessive disorder resulting from malformation of the lymphatic system. The characteristic signs of Hennekam syndrome are lymphangiectasia, lymph edema, facial anomalies, and mental retardation. This is a case in which a patient presented with left-arm lymphedema, facial-feature anomalies, and multiple organ lymphangiectasia consistent with symptoms of Hennekam syndrome. There is no curative therapy at this time, but rehabilitative treatments including complete decongestive therapy for edema control appeared to be beneficial.
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PMID:Hennekam Syndrome: A Case Report. 2956 Mar 40

The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteolytic cleavage and activation of VEGF-C. The fact that FAT4, CCBE1, and ADAMTS3 mutations underlie Hennekam syndrome suggested that all 3 genes might function in a common pathway. We identified FAT4 as a target gene of GATA-binding protein 2 (GATA2), a key transcriptional regulator of lymphatic vascular development and, in particular, lymphatic vessel valve development. Here, we demonstrate that FAT4 functions in a lymphatic endothelial cell-autonomous manner to control cell polarity in response to flow and is required for lymphatic vessel morphogenesis throughout development. Our data reveal a crucial role for FAT4 in lymphangiogenesis and shed light on the mechanistic basis by which FAT4 mutations underlie a human lymphedema syndrome.
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PMID:Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow. 3218 15