How rare is Opitz G/BBB syndrome?

Opitz G/BBB syndrome is classified as not well established. The estimated prevalence is approximately Unknown. Because rare disease data can be limited, actual numbers may differ from published estimates.

How is Opitz G/BBB syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Opitz G/BBB syndrome?

Information about treatment options is currently limited for this condition.

What complications can arise from Opitz G/BBB syndrome?

Opitz G/BBB syndrome can lead to complications due to the malformations in the throat and esophagus. These issues may affect how a person breathes and swallows, which can result in difficulties with eating and speaking. It's important for families to monitor these aspects closely and seek help from specialists if needed.

How does Opitz G/BBB syndrome affect daily life?

Living with Opitz G/BBB syndrome may require special attention to certain daily activities, especially those involving eating and speaking. Children might need help with swallowing and may benefit from speech therapy. Families often work with healthcare providers to create a supportive environment that addresses these challenges.

What is the life expectancy for someone with Opitz G/BBB syndrome?

Currently, there is limited information about the life expectancy for individuals with Opitz G/BBB syndrome. The prognosis can vary widely depending on the severity of symptoms and associated complications. Regular medical care and monitoring can help manage health issues and improve quality of life.

What specialists should we consult for Opitz G/BBB syndrome?

For Opitz G/BBB syndrome, it is important to consult specialists who understand the specific needs of the condition. This may include geneticists, speech therapists, and specialists in throat and esophagus issues. A team approach can help address the various challenges faced by individuals with this syndrome.

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Opitz G/BBB syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include very common findings: Hypertelorism, Long philtrum, Wide nasal bridge, and Prominent forehead; and common findings: Hypospadias, Cleft palate, Widow's peak, and Anteverted nares and others. 75 total HPO annotations.

Organ System	Phenotype Count	Example Features
Head and neck	7	Cleft palate, Abnormal facial shape, Laryngeal cleft
Brain and nerves	7	Intellectual disability, Specific learning disability, Enlarged brain ventricles (ventriculomegaly)
Heart and blood vessels	4	Abnormal heart morphology, Ventricular septal defect, Atrial septal defect
Eyes	2	Ptosis, Strabismus
Kidneys and urinary system	2	Abnormality of the urinary system, Abnormality of the genitourinary system
Digestive system	2	Difficulty swallowing (dysphagia), Feeding difficulties in infancy
Growth and development	1	Short stature
Ears	1	Hearing loss (hearing impairment)
Pregnancy and birth	1	Congenital diaphragmatic hernia
Lungs and breathing	1	Recurrent aspiration pneumonia
Bones and joints	1	Vertebral segmentation defect

GeneReviews

Clinical Guidance

MID1-related Opitz G/BBB syndrome (MID1-OS) is characterized by facial anomalies, genitourinary abnormalities, laryngotracheoesophageal defects, and congenital heart defects. Developmental delay and intellectual disability are common. Clinical manifestations are most evident in affected males, although wide clinical variability has been described, even among members of the same family. To date, 90 individuals have been identified with a pathogenic variant in MID1 and are reported together with their clinical synopsis [, , , , , , , , , , , , , , ].

Table 2.

MID1-Related Opitz G/BBB Syndrome: Frequency of Select Features in Males

Feature | % of Males w/Feature

Hypertelorism | ~100%

Hypospadias | 90%

Laryngotracheoesophageal defects | 70%

Cleft lip /or palate | 48%

Source: GeneReviews — "MID1-Related Opitz G/BBB 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

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care .

Suggestive Findings

MID1-related Opitz G/BBB syndrome (MID1-OS) should be suspected in a male with the following clinical and imaging findings and family history.

Clinical findings

Source: GeneReviews — "MID1-Related Opitz G/BBB Syndrome"

GeneReviews

Differential Diagnosis

Table 3. Genes of Interest in the Differential Diagnosis of MID1-Related Opitz G/BBB Syndrome

Gene/ Genetic Mechanism	Disorder	MOI	Features of This Disorder
Overlapping w/MID1-OS	Distinguishing from MID1-OS 22q11.2 deletion	22q11.2 deletion syndrome1	AD
CASK	CASK-related FG syndrome/ XL ID ± nystagmus2 (See CASK Disorders.)	XL

Biomarker and diagnostic research for Opitz G/BBB 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 Opitz G/BBB 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 MID1-related Opitz G/BBB syndrome (MID1-OS), the evaluations summarized in by a multidisciplinary team (including craniofacial surgeon, ophthalmologist, pediatrician, pediatric urologist, cardiologist, pulmonologist, speech-language pathologist, and clinical geneticist) are recommended if they have not already been performed. Table 4. MID1-Related Opitz G/BBB Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern	Evaluation	Comment
General	Past medical history physical exam w/attention to palate, heart, genitourinary system, lower respiratory system	Cleft lip /or palate
Urogenital abnormalities	Assessment of hypospadias by urologist, incl ultrasound exam to evaluate for urinary tract dysfunction in males w/severe hypospadias	—
LTE defects	Laryngoscopy chest x-ray in persons who have choking w/feeding, recurrent pneumonia, /or aspiration	—
Developmental delay	Developmental eval	—
Congenital heart disease	Echocardiogram	—

Source: GeneReviews — "MID1-Related Opitz G/BBB Syndrome"

GeneReviews

Therapies Under Investigation

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

Source: GeneReviews — "MID1-Related Opitz G/BBB Syndrome"

Clinical Trials

5 trials found

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

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. MID1-Related Opitz G/BBB Syndrome: Recommended Surveillance

System/Concern	Evaluation	Frequency
Cleft lip/palate	Craniofacial team follow up for those w/cleft lip/palate	Per craniofacial specialists
Hearing	Audiology eval	Annually or as needed
Urogenital abnormalities	Urology follow up for those w/significant hypospadias /or other urinary tract abnormalities	Per urologist /or nephrologist
LTE defects	Gastroenterology, pulmonology, /or surgical team follow up for those w/LTE defects	As needed
Development	Monitoring of developmental progress educational needs	At each visit
Congenital heart disease	Cardiac follow up for those w/cardiac defects	Per cardiologist
Anal abnormalities	Gastroenterology /or surgical follow up for those w/anal defects	Per gastroenterologist or surgical team
Ophthalmologic manifestations	Ophthalmology assessment	Per ophthalmologist
Family/Community	Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).	At each visit LTE = laryngotracheoesophageal

Source: GeneReviews — "MID1-Related Opitz G/BBB Syndrome"

Phenotype severity distribution: 4 very common features, 16 common features.

Estimated prevalence: Unknown (Unknown prevalence).

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.

5 clinical trials registered, 2 recruiting. Interventions under study include other interventions. Pipeline includes 1 PHASE2. Research is primarily sponsored by academic and government institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT01773278](https://clinicaltrials.gov/study/NCT01773278)	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)	PHASE2	University of Colorado, Denver	UNKNOWN
[NCT03303716](https://clinicaltrials.gov/study/NCT03303716)	ASXL-Related Disorders Natural History Study	—	University of California, Los Angeles	RECRUITING
[NCT01793168](https://clinicaltrials.gov/study/NCT01793168)	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford	—	Sanford Health	RECRUITING
[NCT03655223](https://clinicaltrials.gov/study/NCT03655223)	Early Check: Expanded Screening in Newborns	—	RTI International	ACTIVE_NOT_RECRUITING
[NCT05047354](https://clinicaltrials.gov/study/NCT05047354)	Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism	—	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	UNKNOWN

59 publications have been identified in PubMed for Opitz G/BBB syndrome. Research spans Basic Science / Preclinical (42%), Case Report / Case Series (25%), and Epidemiology / Natural History (16%).

Research Type	Count	% of Total
Laboratory research	23	42%
Patient case studies	14	25%
Disease patterns and progression	9	16%
Research summaries	5	9%
Testing and diagnosis research	2	4%
Other research	1

Recent Publications

Marsal-Olivan A (2026). [PMID: 42071123](https://pubmed.ncbi.nlm.nih.gov/42071123/). *J Assist Reprod Genet*. [Diagnostic / Biomarker]
Li A (2026). [PMID: 41506459](https://pubmed.ncbi.nlm.nih.gov/41506459/). *J Steroid Biochem Mol Biol*. [Basic Science / Preclinical]
Martinková J (2026). [PMID: 42237847](https://pubmed.ncbi.nlm.nih.gov/42237847/). *Mol Genet Genomic Med*. [Case Report / Case Series]
Fernández-Hernández L (2026). [PMID: 41751615](https://pubmed.ncbi.nlm.nih.gov/41751615/). *Genes (Basel)*. [Case Report / Case Series]
Thambar S (2026). [PMID: 39503249](https://pubmed.ncbi.nlm.nih.gov/39503249/). *Orthod Craniofac Res*. [Basic Science / Preclinical]
Kovács E (2026). [PMID: 41751549](https://pubmed.ncbi.nlm.nih.gov/41751549/). *Genes (Basel)*. [Epidemiology / Natural History]
Yaeger JDW (2026). [PMID: 42105949](https://pubmed.ncbi.nlm.nih.gov/42105949/). *J Lipid Res*. [Basic Science / Preclinical]
Erickson RP (2026). [PMID: 41651789](https://pubmed.ncbi.nlm.nih.gov/41651789/). *Am J Med Genet A*. [Review / Meta-Analysis]
Mirsky E (2026). [PMID: 41856964](https://pubmed.ncbi.nlm.nih.gov/41856964/). *J Addict Med*. [Epidemiology / Natural History]
Wu Q (2026). [PMID: 41842826](https://pubmed.ncbi.nlm.nih.gov/41842826/). *J Craniofac Surg*. [Case Report / Case Series]

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:2745

GARD

Genetic and Rare Diseases Info Center

GARD:193

Questions for Your Care Team

→Are any of the 5 active clinical trials a good fit for my situation?
→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 Opitz G/BBB syndrome

Opitz G/BBB syndrome is a condition that causes several physical differences which are often present at birth. It is marked by malformations of the midline of the body, affecting areas such as the face and the structures of the throat. People with this condition may have wide-set eyes (hypertelorism) and abnormalities in the throat and esophagus, which can influence how they breathe and swallow. There are two main types of this syndrome that are genetically similar but inherited in different ways. One type is X-linked, meaning the gene responsible is on the X chromosome, while the other type is autosomal dominant and can be passed down from one affected parent. This information helps in understanding how the condition may be passed through families.

People with Opitz G/BBB syndrome often show signs that affect the middle of the body. Common features include wide-set eyes (hypertelorism), defects that affect the voice box, windpipe, and esophagus (laryngo-tracheo-esophageal abnormalities), and in males, an unusual placement of the urethral opening (hypospadias).

This condition is caused by genetic changes. There are two forms based on the pattern of inheritance: the X-linked form, where the responsible genetic change is on the X chromosome, and the autosomal dominant form, where a change in one copy of the gene is enough to cause the condition. Details about specific genes are not available from the current information. Associated genes include MID1.

Kisho

Opitz G/BBB syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

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

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Opitz G/BBB syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

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

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

What is Opitz G/BBB syndrome?

What are the symptoms of Opitz G/BBB syndrome?

What causes Opitz G/BBB syndrome?

How rare is Opitz G/BBB syndrome?

How is Opitz G/BBB syndrome diagnosed?

Are there treatments for Opitz G/BBB syndrome?

What complications can arise from Opitz G/BBB syndrome?

How does Opitz G/BBB syndrome affect daily life?

What is the life expectancy for someone with Opitz G/BBB syndrome?

What specialists should we consult for Opitz G/BBB syndrome?