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features of Donnai–Barrow syndrome are probably caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of the nonfunctional megalin protein. However, it is unclear how these abnormalities result in the specific signs and symptoms of the disorder.
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developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai–Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.
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Individuals with Donnai–Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the
139:
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In almost all cases, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms
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In almost all people with Donnai–Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability
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Mutations in the LRP2 gene cause Donnai–Barrow syndrome. The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and
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Megalin is embedded in the membrane of cells that line the surfaces and cavities of the body (epithelial cells). The receptor helps move its ligands from the cell surface into the cell (endocytosis). It is active in the development and function of many parts of the body, including the brain and
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LRP2 gene mutations that cause Donnai–Barrow syndrome are believed to result in the absence of functional megalin protein. The lack of functional megalin in the renal tubules causes megalin's various ligands to be excreted in the urine rather than being absorbed back into the bloodstream. The
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People with Donnai–Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the
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their receptors trigger signals that affect cell development and function. Megalin has many ligands involved in various body processes, including the absorption of vitamins A and D, immune functioning, stress response, and the transport of fats in the bloodstream.
147:(UPD). UPD occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development.
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A condition previously classified as a separate disorder called facio-oculo-acoustico-renal (FOAR) syndrome has also been found to be caused by LRP2 mutations. FOAR syndrome is now considered to be the same disorder as Donnai–Barrow syndrome.
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98:, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
253:; Barrow, M (1993). "Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?".
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spinal cord (central nervous system), eyes, ears, lungs, intestine, reproductive system, and the small tubes in the kidneys where urine is formed (renal tubules).
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One individual with Donnai–Barrow syndrome was found to have inherited both copies of the mutated gene from his father as a result of a genetic change called
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455:"Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others"
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Donnai–Barrow syndrome appears to be a rare disorder. A few dozen affected individuals have been reported in many regions of the world.
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back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).
507:"Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes"
290:"Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes"
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Chassaing, N; Lacombe, D; Carles, D; Calvas, P; Saura, R; Bieth, E (2003). "Donnai-Barrow syndrome: four additional patients".
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550:"Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy"
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630:"A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome: clinical features and differential diagnosis"
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Kantarci, S; Ragge, NK; Thomas, NS; Robinson, DO; Noonan, KM; Russell, MK; Donnai, D; Raymond, FL; Walsh, CA (2008).
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Kantarci, S; Al-Gazali, L; Hill, RS; Donnai, D; Black, GC; Bieth, E; Chassaing, N; Lacombe, D; Devriendt, K (2007).
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This article incorporates text from the United States
National Library of Medicine, which is in the public domain.
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Patel, N; Hejkal, T; Katz, A; Margalit, E (2007). "Ocular manifestations of Donnai-Barrow syndrome".
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Kantarci, S; Donnai, D; Noonan, KM; Pober, BR; Pagon, RA; Bird, TC; Dolan, CR; Stephens, K (1993).
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The sources below were used to develop this article's condition summary on Donnai-Barrow syndrome.
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Donnai–Barrow syndrome is inherited in an autosomal recessive manner.
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Birth
Defects Research. Part A, Clinical and Molecular Teratology
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Kantarci S; Al-Gazali L; Hill RS; et al. (August 2007).
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Junctional epidermolysis bullosa with pyloric atresia
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1169:Congenital insensitivity to pain with anhidrosis
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554:American Journal of Medical Genetics Part A
418:American Journal of Medical Genetics Part A
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898:Follicle-stimulating hormone insensitivity
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628:Pober, BR; Longoni, M; Noonan, KM (2009).
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1621:Syndromes with craniofacial abnormalities
1579:X-linked severe combined immunodeficiency
1355:TNF receptor associated periodic syndrome
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76:is a genetic disorder first described by
704:This article incorporates text from the
1367:Selective immunoglobulin A deficiency 2
958:Aspirin-exacerbated respiratory disease
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1542:EDAR hypohidrotic ectodermal dysplasia
1470:Familial exudative vitreoretinopathy 4
1027:Familial exudative vitreoretinopathy 1
1234:Hereditary hemorrhagic telangiectasia
1210:Persistent Müllerian duct syndrome II
981:Jansen's metaphyseal chondrodysplasia
7:
1555:Nevoid basal-cell carcinoma syndrome
1004:Familial hypocalciuric hypercalcemia
255:American Journal of Medical Genetics
1318:Surfactant metabolism dysfunction 4
1611:Cell surface receptor deficiencies
1567:BMPR1A juvenile polyposis syndrome
1488:LDLR Familial hypercholesterolemia
94:This disorder is characterized by
25:
878:Luteinizing hormone insensitivity
679:U.S. National Library of Medicine
672:"Bulleted reference list (above)"
370:U.S. National Library of Medicine
946:Nephrogenic diabetes insipidus 1
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158:
886:Male-limited precocious puberty
380:from the original on 2020-10-21
1273:Leber's congenital amaurosis 1
1185:Gastrointestinal stromal tumor
1:
683:National Institutes of Health
472:10.1016/S1028-4559(07)60004-7
374:National Institutes of Health
1626:Syndromes affecting hearing
1616:Syndromes affecting the eye
866:Congenital hypothyroidism 1
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1525:Glanzmann's thrombasthenia
1505:Immunoglobulin superfamily
1157:Rabson–Mendenhall syndrome
839:G protein-coupled receptor
593:Journal of Child Neurology
1379:Hyper-IgM syndrome type 3
106:and developmental delay.
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37:
1454:Cenani–Lenz syndactylism
1296:Type I cytokine receptor
934:Hirschsprung's disease 2
763:C536390 C536390, C536390
605:10.1177/0883073807301933
490:"Donnai-Barrow Syndrome"
359:"Donnai-Barrow syndrome"
1136:Thanatophoric dysplasia
930:Waardenburg syndrome 4a
267:10.1002/ajmg.1320470518
96:unusual facial features
1590:cell surface receptors
1442:Donnai–Barrow syndrome
1116:Jackson–Weiss syndrome
1104:Antley–Bixler syndrome
1088:KAL2 Kallmann syndrome
1042:Enzyme-linked receptor
882:Leydig cell hypoplasia
206:This section is empty.
167:This section is empty.
74:Donnai–Barrow syndrome
33:Donnai–Barrow syndrome
18:Donnai-Barrow syndrome
902:XX gonadal dysgenesis
830:Cell surface receptor
1248:Loeys–Dietz syndrome
566:10.1002/ajmg.a.32381
430:10.1002/ajmg.a.20266
712:), which is in the
1218:TGF beta receptors
773:External resources
646:10.1002/bdra.20534
145:uniparental disomy
140:of the condition.
135:Inherited mutation
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1132:Hypochondroplasia
1108:Pfeiffer syndrome
1084:Pfeiffer syndrome
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90:Presentation
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842:(including
366:MedlinePlus
78:Dian Donnai
1605:Categories
1045:(including
689:2010-12-19
685:. May 2009
294:Nat. Genet
237:References
190:Management
1398:TNFRSF13B
1386:TNFRSF13C
1362:TNFRSF13B
251:Donnai, D
151:Diagnosis
53:Specialty
1586:See also
1516:Integrin
1350:TNFRSF1A
1288:JAK-STAT
1222:Endoglin
782:Orphanet
675:(online)
664:19089858
621:28446743
613:17621530
584:18553518
541:17632512
498:20301732
481:17638618
446:38409652
438:12923867
378:Archived
362:(online)
324:17632512
1509:AGM3, 6
1410:TNFRSF6
1374:TNFRSF5
1014:Class F
991:Class C
968:Class B
853:Class A
844:hormone
708: (
681:of the
655:2882234
575:2891749
532:2891728
372:of the
315:2891728
275:8266995
1562:BMPR1A
1313:CSF2RA
1268:GUCY2D
1244:TGFBR2
1240:TGFBR1
953:PTGER2
752:222448
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114:Causes
60:
1574:IL2RG
1550:PTCH1
1403:CVID2
1391:CVID4
1230:SMAD4
1226:Alk-1
1205:AMHR2
1164:NTRK1
1123:FGFR3
1095:FGFR2
1079:FGFR1
976:PTH1R
941:AVPR2
921:EDNRB
909:GnRHR
873:LHCGR
617:S2CID
442:S2CID
384:8 May
1537:EDAR
1520:LAD1
1483:LDLR
1461:LRP5
1449:LRP4
1437:LRP2
1196:STPK
1147:INSR
1067:ROR2
1022:FZD4
999:CASR
893:FSHR
861:TSHR
787:2143
758:MeSH
747:OMIM
660:PMID
609:PMID
580:PMID
558:146A
537:PMID
494:PMID
477:PMID
434:PMID
422:121A
386:2021
320:PMID
271:PMID
83:LRP2
1432:LRP
1326:MPL
1176:KIT
1058:RTK
650:PMC
642:doi
601:doi
570:PMC
562:doi
527:PMC
519:doi
467:doi
426:doi
310:PMC
302:doi
263:doi
212:.
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