How is Rabson-Mendenhall syndrome inherited?

Rabson-Mendenhall 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 Rabson-Mendenhall syndrome?

Rabson-Mendenhall 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 Rabson-Mendenhall syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Rabson-Mendenhall syndrome?

Information about treatment is currently limited for this condition.

What complications can arise from Rabson-Mendenhall syndrome?

Rabson-Mendenhall syndrome can lead to serious complications due to extreme insulin resistance. This can cause problems with blood sugar levels, which may result in diabetes-related issues. Since information about specific complications is limited, it's important for families to work closely with healthcare providers to monitor and manage any potential health concerns.

How does Rabson-Mendenhall syndrome affect daily life?

Living with Rabson-Mendenhall syndrome can be challenging due to the body's difficulty in using insulin. This may require careful monitoring of blood sugar levels and possibly special dietary considerations. Families may need to adapt their daily routines to ensure proper management of the condition and maintain a healthy lifestyle.

What is the life expectancy for someone with Rabson-Mendenhall syndrome?

Currently, there is limited information available about the life expectancy of individuals with Rabson-Mendenhall syndrome. The severity of insulin resistance and related health issues can vary greatly among individuals. It is essential for families to consult with healthcare professionals to understand more about the specific situation and prognosis.

Are there specialists that should be involved in managing Rabson-Mendenhall syndrome?

Yes, managing Rabson-Mendenhall syndrome often requires a team of specialists. Endocrinologists, who focus on hormone-related conditions, are particularly important for helping with insulin management. Additionally, dietitians may assist with creating a suitable meal plan to support overall health and well-being.

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Rabson-Mendenhall syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

Rabson-Mendenhall syndrome

MONDO:0009874

Also known as:Mendenhall syndromepineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities

Overview

Rabson-Mendenhall syndrome belongs to the group of extreme insulin-resistance syndromes (which also includes leprechaunism, the lipodystrophies, and the type A and B insulin resistance syndromes).

GeneticsAutosomal recessive · INSR (chr 19)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include: Short stature, Long penis, Global developmental delay, and Hyperglycemia and 17 more.

Organ System	Phenotype Count	Example Features
Head and neck	3	Coarse facial features, High palate, Mandibular prognathia
Hormones

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

INSR encodes insulin receptor (1,382 aa). Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Highest expression in Spleen (90.9 TPM) and Ovary (80.2 TPM).

Rabson-Mendenhall syndrome is associated with mutations in the INSR gene on chromosome 19.

The INSR protein participates in BIN2(1-253)insRVSLGSILSVSS-PDGFRB(572-1106) fusion and p-12Y-BIN2(1-253)insRVSLGSILSVSS-PDGFRB(572-1106) fusion pathways.

INSR is classified as a druggable target (Clinically Actionable, Druggable Genome, Enzyme, External Side Of Plasma Membrane, Kinase, Transcription Factor, Transporter, and Tyrosine Kinase categories) with score 1.5.

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

INSR-related severe insulin resistance syndrome (INSR-SIRS) should be suspected in individuals with the following , , and findings of Donohue syndrome or Rabson-Mendenhall syndrome (RMS).

Clinical Findings

Donohue syndrome

Source: GeneReviews — "INSR-Related Severe Insulin Resistance Syndrome"

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 Rabson-Mendenhall 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 INSR-related severe insulin resistance syndrome (INSR-SIRS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

INSR-Related Severe Insulin Resistance Syndrome: Recommended Evaluations Following Initial Diagnosis

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. INSR-Related Severe Insulin Resistance Syndrome: Recommended Surveillance

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 Rabson-Mendenhall syndrome.

42 publications have been identified in PubMed for Rabson-Mendenhall syndrome. Research spans Case Report / Case Series (31%), Epidemiology / Natural History (24%), and Review / Meta-Analysis (14%).

Research Type	Count	% of Total
Patient case studies	13	31%

Data assembled from 7 of 12 sources · Last updated Sep 20, 2026, 3:03 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:262190

Orphanet

European rare disease database

Orphanet:769

GARD

Genetic and Rare Diseases Info Center

GARD:226

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 Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome is a rare condition that falls under the group of extreme insulin-resistance syndromes. It is known by several names including Rabson-Mendenhall syndrome, Mendenhall syndrome, pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities. This condition is part of a broader group that includes disorders such as leprechaunism, the lipodystrophies, and the type A and B insulin resistance syndromes. The syndrome involves a significant resistance to insulin, which is important for regulating blood sugar in the body. The information available comes mainly from established sources like the Online Mendelian Inheritance in Man (OMIM) and GeneReviews, highlighting its connection with insulin regulation. While details about the full range of symptoms and management strategies are still limited, understanding that this syndrome impacts the body’s uptake and use of insulin is a key aspect. This basic overview serves to provide an introduction to what is known about this complex condition.

Information about symptoms is currently limited for this condition.

Rabson-Mendenhall syndrome is caused by an extreme resistance to insulin, which is partly linked to genetic factors. The INSR gene, which plays a critical role in insulin function, is known to be involved. Changes in this gene can lead to poor insulin signaling, placing individuals in the group of extreme insulin-resistance syndromes. Associated genes include INSR.

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GeneReviews

Clinical Guidance

INSR-related severe insulin resistance syndrome (INSR-SIRS) comprises a phenotypic continuum from the severe phenotype of Donohue syndrome to the milder phenotype of Rabson-Mendenhall syndrome (RMS). To date, fewer than 100 individuals have been identified with INSR-SIRS . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. INSR-Related Severe Insulin Resistance Syndrome: Comparison of Phenotypes by Select Features

Feature	Donohue Syndrome	Rabson-Mendenhall Syndrome
Hyperinsulinism	100%	100%
Diabetic ketoacidosis	+	100%
Genital enlargement	+	100%
Hypothyroidism	+	50% Growth
Intrauterine growth deficiency	100%	+
Postnatal growth deficiency	100%	60%-80% Neurologic
Hypotonia	100%	+
Developmental delay	100%	100%
Intellectual disability	100%	50%
Dysmorphic facial features	100%	100%
Integument abnormalities	100%	100%
Organomegaly	100%	60%-80%
Rectal hypertrophy /or prolapse	100%	+ Based on , , , , , , , + = reported feature; incidence unknown Donohue syndrome is characterized by severe insulin resistance, growth failure, hypotonia, developmental delay, characteristic facies, and organomegaly. Endocrine manifestations.

Source: GeneReviews — "INSR-Related Severe Insulin Resistance Syndrome"

Differential Diagnosis

The differential diagnosis of INSR-related severe insulin resistance syndrome (INSR-SIRS) includes many rare disorders with hirsutism, severe growth deficiency, and developmental delay with other syndromic features, some of which are summarized in . Table 3. Selected Disorders of Interest in the Differential Diagnosis of INSR-Related Severe Insulin Resistance Syndrome

Gene(s)/ Genetic Mechanism	Disorder	MOI	Clinical Features of Disorder
Overlapping w/INSR-SIRS	Distinguishing from INSR-SIRS 11p15.5 hypomethylation,maternal UPD7, other causes1	Silver-Russell syndrome (SRS)	See footnote 1.
UCP2	Familial hyperinsulinism (FHI)	ADAR	Congenital hyperinsulinemia; Hypoglycemia (ranging from severe neonatal-onset disease to childhood-onset disease w/mild symptoms in FHI)3
Insulin levels are usually much higher in DS/RMS. AGPAT2BSCL2CAV1CAVIN1 (PTRF)	Berardinelli-Seip congenital lipodystrophy (BSCL) (OMIM PS608594)	AR	Congenital hyperinsulinemia; Insulin resistance4; Hepatomegaly (due to hepatic steatosis skeletal muscle hypertrophy in BSCL); Hypertrophic cardiomyopathy5
IGF1R	Resistance to insulin-like growth factor 1 (OMIM 270450)	ARAD	IUGR postnatal growth deficiency; Mildly impaired glucose tolerance6; Delayed psychomotor development; Mild dysmorphic features

Source: GeneReviews — "INSR-Related Severe Insulin Resistance Syndrome"

Kisho

Rabson-Mendenhall syndrome

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

FAQ

Frequently Asked Questions

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Endocrine

Nutrition/Feeding

Development

Cardiac

Renal

Liver/GI function

Dental

Clinical Guidance

Therapies Under Investigation

Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1)

Clinical Trials

Recent Publications

Rabson-Mendenhall syndrome

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

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 Rabson-Mendenhall syndrome?

What are the symptoms of Rabson-Mendenhall syndrome?

What causes Rabson-Mendenhall syndrome?

How is Rabson-Mendenhall syndrome inherited?

How rare is Rabson-Mendenhall syndrome?

How is Rabson-Mendenhall syndrome diagnosed?

Are there treatments for Rabson-Mendenhall syndrome?

What complications can arise from Rabson-Mendenhall syndrome?

How does Rabson-Mendenhall syndrome affect daily life?

What is the life expectancy for someone with Rabson-Mendenhall syndrome?

Are there specialists that should be involved in managing Rabson-Mendenhall syndrome?

Clinical Guidance

Explore clinical features

Clinical Guidance

Differential Diagnosis

Endocrine

Nutrition/Feeding

Development

Cardiac

Renal

Liver/GI function

Dental

Clinical Guidance

Therapies Under Investigation

Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1)

Clinical Trials

Recent Publications