How is Donnai-Barrow syndrome inherited?

Donnai-Barrow syndrome follows an autosomal recessive inheritance pattern. This means a child must inherit a copy of the altered gene from both parents to develop the condition. Parents who each carry one copy typically do not show symptoms.

How rare is Donnai-Barrow syndrome?

Donnai-Barrow syndrome is classified as very rare. The estimated prevalence is approximately <1 in 1,000,000. Because rare disease data can be limited, actual numbers may differ from published estimates.

How is Donnai-Barrow syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Donnai-Barrow syndrome?

Information about treatment is currently limited for this condition.

What complications can arise from Donnai-Barrow syndrome?

Donnai-Barrow syndrome can lead to several complications due to its effects on various body systems. These may include serious issues like congenital diaphragmatic hernia, which affects breathing, and omphalocele, where organs are outside the body. Additionally, problems with brain development, such as an absent corpus callosum, can lead to challenges in learning and development.

How does Donnai-Barrow syndrome affect daily life for patients?

Living with Donnai-Barrow syndrome can be challenging due to its various symptoms. Patients may need special support for hearing loss, vision problems, and potential intellectual disabilities. Regular check-ups with healthcare providers are important to manage these issues and ensure that the patient receives the best care possible.

What is the prognosis for individuals with Donnai-Barrow syndrome?

The prognosis for individuals with Donnai-Barrow syndrome can vary widely depending on the severity of their symptoms. Some may have significant health challenges, while others may lead relatively stable lives with appropriate support. However, detailed information about long-term outcomes is still being studied, so it’s important to stay in touch with medical professionals.

Are there any specialists that families should consult for Donnai-Barrow syndrome?

Families dealing with Donnai-Barrow syndrome should consider consulting a team of specialists. This may include geneticists for understanding the genetic aspects, pediatricians for overall health, and specialists in developmental disorders. An audiologist may also be important for managing hearing loss, while an ophthalmologist can help with any eye problems.

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Donnai-Barrow syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Hearing loss (hearing impairment), Non-acidotic proximal tubulopathy, Agenesis of corpus callosum, and Protein in the urine (proteinuria) and others; and very common findings: Wide anterior fontanel, Short nose, Broad nasal tip, and Global developmental delay and others. 37 total HPO annotations.

Organ System	Phenotype Count	Example Features
Eyes	3	Retinal detachment, Cataract, Retinal dystrophy
Brain and nerves	3	Seizure, Global developmental delay, Depressed nasal bridge
Ears	2	Hearing loss (hearing impairment), Inner ear hearing loss (sensorineural hearing impairment)
Kidneys and urinary system	2	Non-acidotic proximal tubulopathy, Protein in the urine (proteinuria)
Heart and blood vessels	1	Ventricular septal defect
Head and neck	1	Macrocephaly
Pregnancy and birth	1	Congenital diaphragmatic hernia
Digestive system	1	Intestinal malrotation

GeneReviews

Clinical Guidance

The following information is based on case reports reviewed in , , , , , , , and . Craniofacial features. Widely spaced eyes, depressed nasal bridge, short nose with a broad and occasionally indented tip, broad forehead, and prominent parietal frontal bossing are characteristic findings and are consistently present in individuals with DBS and confirmed biallelic LRP2 pathogenic variants. Downslanted palpebral fissures and low-set posteriorly angulated ears are very frequent findings. While some of these features may change over time, the facial gestalt remains characteristic in the few reported adults. Ophthalmologic abnormalities.

Source: GeneReviews — "Donnai-Barrow Syndrome"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

Donnai-Barrow syndrome (DBS) should be suspected in individuals with the following clinical and radiographic features. No single clinical feature is pathognomonic for DBS, nor have diagnostic criteria been formalized.

Clinical features

Source: GeneReviews — "Donnai-Barrow Syndrome"

GeneReviews

Differential Diagnosis

Donnai-Barrow syndrome (DBS) is associated with congenital diaphragmatic hernia (CDH). Table 2. Disorders to Consider in the Differential Diagnosis of Donnai-Barrow Syndrome

Differential Diagnosis Disorder	Gene(s)	MOI	Clinical Features of Disorder
Overlapping w/DBS	Distinguishing from DBS Pallister-Killian syndrome (12p tetrasomy mosaicism) (OMIM 601803)	NA	Sporadic
Fryns syndrome	Unknown	AR	Diaphragmatic defects; Occasionally agenesis of corpus callosum; Widely spaced eyes
GPSM2	AR	Sensorineural hearing loss; Partial agenesis of corpus callosum

Genetic testing for LRP2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for Donnai-Barrow syndrome has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for Donnai-Barrow syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Donnai-Barrow syndrome (DBS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Donnai-Barrow Syndrome

System/Concern	Evaluation	Comment
Eyes	Ophthalmologic eval	Frequent, detailed ophthalmologic exams to assess visual acuity retinal integrity
ENT	Audiologic eval	Serial eval to monitor progression/degree of hearing loss
Neurologic	Neuroimaging	Preferably MRI EEG
Renal	Serum blood urea nitrogen (BUN), serum creatinine, urinalysis	To assess kidney function Serum vitamin A vitamin D (25-hydroxyvitamin D)
Other	Developmental eval	Developmental testing appropriate for degree of vision hearing impairments Consultation w/clinical geneticist /or genetic counselor
Treatment of Manifestations in Individuals with Donnai-Barrow Syndrome Manifestation/Concern	Treatment	Considerations/Other
Diaphragmatic hernia	Surgical repair1	Postoperative assessment of respiratory function to determine if there is risk for long-term respiratory problems
Omphalocele	Surgical repair1	—
Myopia	Corrective lenses	Peripheral laser photocoagulation may minimize risk of retinal detachment resulting from high myopia. Retinal
detachment	Treatment per ophthalmologist	—
Hearing loss	Hearing aid /or cochlear implant per ENT	—
Seizures	Standardized treatment w/ASMs by experienced neurologist	Many different ASMs may be effective; none has been shown effective specifically for this disorder.
Hypovitaminoses	Supplementation as needed	Monitoring of serum vitamins A D (25-hydroxyvitamin D) ASM = anti-seizure medication; ENT = ear, nose, and throat (specialist) Surgical repair of omphalocele and/or diaphragmatic hernia appears to pose no greater risk than repair of these defects in children with other genetic syndromes.

Source: GeneReviews — "Donnai-Barrow Syndrome"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Donnai-Barrow Syndrome"

Clinical Trials

View trials for Donnai-Barrow syndrome

Explore Trials

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with DBS

System/Concern	Evaluation	Frequency
Eyes	Ophthalmologic eval	Per ophthalmologist determined by findings present
ENT	Audiologic exams	Data on natural history possible progression of hearing loss are not currently available; thus, no frequency for monitoring has been established.
Renal	Measurement of serum BUN, creatinine, urinalysis, serum vitamin A D	Per nephrologist determined by findings present Miscellaneous/
Other	Monitoring of developmental progress educational needs	—

Source: GeneReviews — "Donnai-Barrow Syndrome"

Phenotype severity distribution: 7 always present features, 6 very common features, 9 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for Donnai-Barrow syndrome.

126 publications have been identified in PubMed for Donnai-Barrow syndrome. Research spans Review / Meta-Analysis (69%), Basic Science / Preclinical (16%), and Case Report / Case Series (6%).

Research Type	Count	% of Total
Research summaries	87	69%
Laboratory research	20	16%
Patient case studies	7	6%
Disease patterns and progression	7	6%
Other research	2	2%
Testing and diagnosis research	2	2%
Clinical study results	1	1%

Recent Publications

Buel KL (2026). [PMID: 41569909](https://pubmed.ncbi.nlm.nih.gov/41569909/). *FP Essent*. [Review / Meta-Analysis]
Anderson EN (2026). [PMID: 41468891](https://pubmed.ncbi.nlm.nih.gov/41468891/). *Am J Hum Genet*. [Basic Science / Preclinical]
Papazachariou A (2026). [PMID: 41128447](https://pubmed.ncbi.nlm.nih.gov/41128447/). *Curr Opin Clin Nutr Metab Care*. [Review / Meta-Analysis]
Lockwood T (2026). [PMID: 41708531](https://pubmed.ncbi.nlm.nih.gov/41708531/). *Ophthalmic Genet*. [Review / Meta-Analysis]
Beenken A (2026). [PMID: 42024452](https://pubmed.ncbi.nlm.nih.gov/42024452/). *JCI Insight*. [Case Report / Case Series]
Amado C (2026). [PMID: 40975490](https://pubmed.ncbi.nlm.nih.gov/40975490/). *Ann Allergy Asthma Immunol*. [Review / Meta-Analysis]
Regenold JT (2026). [PMID: 42194575](https://pubmed.ncbi.nlm.nih.gov/42194575/). *J Clin Med*. [Review / Meta-Analysis]
Altintas A (2026). [PMID: 41691905](https://pubmed.ncbi.nlm.nih.gov/41691905/). *Curr Opin Immunol*. [Review / Meta-Analysis]
Huang AY (2025). [PMID: 40020243](https://pubmed.ncbi.nlm.nih.gov/40020243/). *Retin Cases Brief Rep*. [Case Report / Case Series]
Pignataro G (2025). [PMID: 41010942](https://pubmed.ncbi.nlm.nih.gov/41010942/). *Medicina (Kaunas)*. [Review / Meta-Analysis]

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:222448

Orphanet

European rare disease database

Orphanet:2143

GARD

Genetic and Rare Diseases Info Center

GARD:1899

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

FAQ

Frequently Asked Questions

Common questions about Donnai-Barrow syndrome

Donnai-Barrow syndrome is a rare condition that affects many parts of the body. It is known for causing a number of birth defects, including changes in facial appearance, eye problems, hearing loss, and issues with brain development such as an absent corpus callosum. In many people with this condition, there are also problems with the diaphragm or abdominal wall, such as congenital diaphragmatic hernia or omphalocele. This condition is seen early in life and can lead to various health challenges. The changes in facial features and other body systems are part of the reason why the syndrome is considered complex. The severity of signs and symptoms can vary among people with Donnai-Barrow syndrome.

Common symptoms of Donnai-Barrow syndrome include distinct facial features, eye problems, hearing loss, and brain structure abnormalities such as the absence of the corpus callosum. Many people also experience congenital diaphragmatic hernia and/or omphalocele. Variable intellectual disabilities may be present as well.

Donnai-Barrow syndrome is linked to changes in a gene called LRP2. These genetic changes are thought to lead to the multiple congenital malformations seen in this condition. However, more detailed information about the exact causes and risk factors is still being studied. Associated genes include LRP2.

Kisho

Donnai-Barrow syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Donnai-Barrow syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is Donnai-Barrow syndrome?

What are the symptoms of Donnai-Barrow syndrome?

What causes Donnai-Barrow syndrome?

How is Donnai-Barrow syndrome inherited?

How rare is Donnai-Barrow syndrome?

How is Donnai-Barrow syndrome diagnosed?

Are there treatments for Donnai-Barrow syndrome?

What complications can arise from Donnai-Barrow syndrome?

How does Donnai-Barrow syndrome affect daily life for patients?

What is the prognosis for individuals with Donnai-Barrow syndrome?

Are there any specialists that families should consult for Donnai-Barrow syndrome?