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Donnai-Barrow syndrome

MedGen UID:
347406
Concept ID:
C1857277
Disease or Syndrome
Synonyms: Diaphragmatic hernia exomphalos absent corpus callosum hypertelorism myopia sensorineural deafness and proteinuria; Faciooculoacousticorenal syndrome
SNOMED CT: Donnai-Barrow syndrome (702418009); Diaphragmatic hernia-exomphalos-corpus callosum agenesis (702418009); Diaphragmatic hernia-exomphalos-hypertelorism syndrome (702418009); Faciooculoacousticorenal syndrome (702418009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LRP2 (2q31.1)
 
Monarch Initiative: MONDO:0009104
OMIM®: 222448
Orphanet: ORPHA2143

Disease characteristics

Excerpted from the GeneReview: Donnai-Barrow Syndrome
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (large anterior fontanelle, wide metopic suture, widow's peak, markedly widely spaced eyes, enlarged globes, downslanted palpebral fissures, posteriorly rotated ears, depressed nasal bridge, and short nose. Ocular complications include high myopia, retinal detachment, retinal dystrophy, and progressive vision loss. Additional common features include agenesis of the corpus callosum, sensorineural hearing loss, intellectual disability, and congenital diaphragmatic hernia and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed. [from GeneReviews]
Authors:
Mauro Longoni  |  Sibel Kantarci  |  Dian Donnai, et. al.   view full author information

Additional descriptions

From OMIM
The faciooculoacousticorenal syndrome (FOAR) was first described as comprising facial anomalies, ocular anomalies, sensorineural hearing loss, and proteinuria. Facial features include prominent brow, short nose, and hypertelorism, and ocular anomalies include myopia, iris hypoplasia, and/or retinal detachment (Regenbogen and Coscas, 1985). Donnai-Barrow syndrome (DBS) was first described as a distinct disorder characterized by diaphragmatic hernia, exomphalos, absent corpus callosum, myopia, and sensorineural deafness. The classic distinguishing features between the 2 disorders were presence of proteinuria and absence of diaphragmatic hernia and corpus callosum anomalies in FOAR (Donnai and Barrow, 1993). However, early reports noted that the 2 disorders shared many phenotypic features and may be identical (e.g., Devriendt et al., 1998). Although there is variability in the expression of some features (e.g., agenesis of the corpus callosum and proteinuria), the disorders are now considered to represent the same entity (Kantarci et al., 2007).  http://www.omim.org/entry/222448
From MedlinePlus Genetics
Donnai-Barrow syndrome is an inherited disorder that affects many parts of the body. This disorder is characterized by unusual facial features, 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.

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 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).

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 and developmental delay.

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 congenital diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the 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.  https://medlineplus.gov/genetics/condition/donnai-barrow-syndrome

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Bicornuate uterus
MedGen UID:
78599
Concept ID:
C0266387
Congenital Abnormality
The presence of a bicornuate uterus.
Non-acidotic proximal tubulopathy
MedGen UID:
870722
Concept ID:
C4025176
Disease or Syndrome
A type of proximal renal tubulopathy characterized by resorption defects leading to glycosuria, aminoaciduria, tubular proteinuria, renal hypophosphatemia, and urate tubular hyporeabsorption without bicarbonate loss.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Partial agenesis of the corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Aplasia/Hypoplasia of the corpus callosum
MedGen UID:
354608
Concept ID:
C1861866
Finding
Absence or underdevelopment of the corpus callosum.
Diaphragmatic eventration
MedGen UID:
8359
Concept ID:
C0011981
Congenital Abnormality
A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Congenital diaphragmatic hernia
MedGen UID:
68625
Concept ID:
C0235833
Congenital Abnormality
The presence of a hernia of the diaphragm present at birth.
Short sternum
MedGen UID:
108394
Concept ID:
C0575497
Finding
Decreased inferosuperior length of the sternum.
Congenital omphalocele
MedGen UID:
162756
Concept ID:
C0795690
Congenital Abnormality
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Infra-orbital crease
MedGen UID:
347408
Concept ID:
C1857280
Finding
Skin crease extending from below the inner canthus laterally along the malar process of the maxilla and zygoma.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Iris coloboma
MedGen UID:
116097
Concept ID:
C0240063
Anatomical Abnormality
A coloboma of the iris.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Hypoplasia of the iris
MedGen UID:
91029
Concept ID:
C0344539
Congenital Abnormality
Congenital underdevelopment of the iris.
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.
Progressive visual loss
MedGen UID:
326867
Concept ID:
C1839364
Finding
A reduction of previously attained ability to see.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDonnai-Barrow syndrome
Follow this link to review classifications for Donnai-Barrow syndrome in Orphanet.

Recent clinical studies

Etiology

Skeby CK, Hummelgaard S, Gustafsen C, Petrillo F, Frederiksen KP, Olsen D, Kristensen T, Ivarsen P, Madsen P, Christensen EI, Nielsen R, Birn H, Glerup S, Weyer K
Kidney Int 2023 Oct;104(4):754-768. Epub 2023 Jul 3 doi: 10.1016/j.kint.2023.06.024. PMID: 37406929
Higham A, Hildebrand GD, Graham-Evans KAJ, Gilbert RD, Horton R, Hunt D, Shears D, Patel CK
Ophthalmic Genet 2022 Apr;43(2):248-252. Epub 2021 Oct 27 doi: 10.1080/13816810.2021.1992787. PMID: 34704885
Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
Khan AO, Ghazi NG
Ophthalmic Genet 2018 Jun;39(3):321-324. Epub 2018 Feb 1 doi: 10.1080/13816810.2018.1430245. PMID: 29388841
Bruce IA, Broomfield SJ, Henderson L, Green KM, Ramsden RT
Cochlear Implants Int 2011 Feb;12(1):60-3. doi: 10.1179/146701010X486534. PMID: 21756462

Diagnosis

Higham A, Hildebrand GD, Graham-Evans KAJ, Gilbert RD, Horton R, Hunt D, Shears D, Patel CK
Ophthalmic Genet 2022 Apr;43(2):248-252. Epub 2021 Oct 27 doi: 10.1080/13816810.2021.1992787. PMID: 34704885
Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
Robinson MK, Coe K, Bradshaw WT
Adv Neonatal Care 2021 Apr 1;21(2):133-141. doi: 10.1097/ANC.0000000000000766. PMID: 32657950
Khalifa O, Al-Sahlawi Z, Imtiaz F, Ramzan K, Allam R, Al-Mostafa A, Abdel-Fattah M, Abuharb G, Nester M, Verloes A, Al-Zaidan H
Eur J Med Genet 2015 May;58(5):293-9. Epub 2015 Feb 13 doi: 10.1016/j.ejmg.2014.12.008. PMID: 25682901
Bruce IA, Broomfield SJ, Henderson L, Green KM, Ramsden RT
Cochlear Implants Int 2011 Feb;12(1):60-3. doi: 10.1179/146701010X486534. PMID: 21756462

Therapy

Canut MI, Alonso-Agesta M, Botella J, Julio G
Eur J Ophthalmol 2020 Jan;30(1):221-223. Epub 2019 Jun 10 doi: 10.1177/1120672119853750. PMID: 31177825

Prognosis

Khan AO, Ghazi NG
Ophthalmic Genet 2018 Jun;39(3):321-324. Epub 2018 Feb 1 doi: 10.1080/13816810.2018.1430245. PMID: 29388841
Dachy A, Paquot F, Debray G, Bovy C, Christensen EI, Collard L, Jouret F
Pediatr Nephrol 2015 Jun;30(6):1027-31. Epub 2015 Mar 31 doi: 10.1007/s00467-014-3037-7. PMID: 25822460
Schrauwen I, Sommen M, Claes C, Pinner J, Flaherty M, Collins F, Van Camp G
Clin Genet 2014 Sep;86(3):282-6. Epub 2013 Sep 23 doi: 10.1111/cge.12265. PMID: 23992033
Bruce IA, Broomfield SJ, Henderson L, Green KM, Ramsden RT
Cochlear Implants Int 2011 Feb;12(1):60-3. doi: 10.1179/146701010X486534. PMID: 21756462

Clinical prediction guides

Long KR, Rbaibi Y, Bondi CD, Ford BR, Poholek AC, Boyd-Shiwarski CR, Tan RJ, Locker JD, Weisz OA
Am J Physiol Renal Physiol 2022 Jan 1;322(1):F14-F26. Epub 2021 Nov 8 doi: 10.1152/ajprenal.00259.2021. PMID: 34747197Free PMC Article
Robinson MK, Coe K, Bradshaw WT
Adv Neonatal Care 2021 Apr 1;21(2):133-141. doi: 10.1097/ANC.0000000000000766. PMID: 32657950
Özdemir S, Tuncer Ü, Sürmelioğlu Ö, Tarkan Ö, Çelik F, Kıroğlu M, Dağkıran M, Şahin P, Tezer N, Akar F
J Int Adv Otol 2019 Dec;15(3):364-367. doi: 10.5152/iao.2019.6577. PMID: 31846912Free PMC Article
Khalifa O, Al-Sahlawi Z, Imtiaz F, Ramzan K, Allam R, Al-Mostafa A, Abdel-Fattah M, Abuharb G, Nester M, Verloes A, Al-Zaidan H
Eur J Med Genet 2015 May;58(5):293-9. Epub 2015 Feb 13 doi: 10.1016/j.ejmg.2014.12.008. PMID: 25682901
Bruce IA, Broomfield SJ, Henderson L, Green KM, Ramsden RT
Cochlear Implants Int 2011 Feb;12(1):60-3. doi: 10.1179/146701010X486534. PMID: 21756462

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