How is Donohue syndrome inherited?

Donohue 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 Donohue syndrome?

Donohue 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 Donohue syndrome diagnosed?

Information about diagnosis is currently limited for this condition.

Are there treatments for Donohue syndrome?

Information about treatment is currently limited for this condition.

What are the specific growth challenges faced by individuals with Donohue syndrome?

Individuals with Donohue syndrome experience significant growth retardation both before birth and after they are born. This means that their growth is much slower than what is typical for their age. These growth challenges are one of the main signs of the condition and can affect their overall development.

How does Donohue syndrome affect daily life for those who have it?

Living with Donohue syndrome can be challenging due to the severe insulin resistance and growth delays. This may require special medical care and monitoring to manage their health. Families may need to adapt daily routines to support their loved ones' unique needs, including regular check-ups and possibly dietary adjustments.

What is the life expectancy for someone with Donohue syndrome?

Information about the life expectancy for individuals with Donohue syndrome is currently limited. Because this condition is rare and varies in severity, it is difficult to provide a clear answer. Families are encouraged to work closely with healthcare providers to understand the specific health needs of their loved ones.

Are there any specialists recommended for managing Donohue syndrome?

While specific recommendations for specialists are not detailed, individuals with Donohue syndrome may benefit from seeing endocrinologists who specialize in hormone and growth disorders. Additionally, working with a team that includes dietitians and genetic counselors can help families manage the condition effectively and support their loved ones' health.

Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

Donohue syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

Donohue syndrome

MONDO:0009517

Also known as:Leprechaunisminsulin receptor, defect 1N

Overview

Leprechaunism is a congenital form of extreme insulin resistance (a group of syndromes that also includes Rabson-Mensenhall syndrome, type A insulin-resistance syndrome, and acquired type B insulin-resistance syndrome) characterized by intrauterine and mainly postnatal severe growth retardation.

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 always present findings: Coarse facial features, Thick vermilion border, Hypertrichosis, and Postnatal growth retardation and others; and common findings: Abdominal distention, Acanthosis nigricans, Rectal prolapse, and Recurrent otitis media and others. 52 total HPO annotations.

Organ System	Phenotype Count	Example Features
Digestive system	6	Abdominal distention, Cholestasis, Liver scarring (fibrosis) (hepatic fibrosis)

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).

Donohue 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 Donohue 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 Donohue syndrome.

11 publications have been identified in PubMed for Donohue syndrome. Research spans Case Report / Case Series (64%), Other (9%), and Review / Meta-Analysis (9%).

Research Type	Count	% of Total
Patient case studies	7	64%

Data assembled from 7 of 12 sources · Last updated Sep 19, 2026, 12:50 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:246200

Orphanet

European rare disease database

Orphanet:508

GARD

Genetic and Rare Diseases Info Center

GARD:6885

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 Donohue syndrome

Donohue syndrome, also known as leprechaunism, is a rare, congenital condition marked by extreme insulin resistance. This condition is characterized by severe growth retardation that begins in the womb and continues after birth. The term leprechaunism underscores some of the unique physical features seen in people affected by this condition. The syndrome falls within a group of disorders that feature severe insulin resistance, which also includes conditions such as Rabson-Mendenhall syndrome and type A insulin-resistance syndrome. Donohue syndrome is connected with mutations in the INSR gene, which plays a key role in how the body responds to insulin, contributing to the distinctive growth challenges seen in affected individuals.

People with Donohue syndrome commonly experience significant growth retardation during both the prenatal period (intrauterine) and after birth (postnatal). This marked delay in growth is one of the primary signs of the condition.

Donohue syndrome is caused by genetic mutations that affect the insulin receptor, specifically involving the INSR gene. These mutations lead to extreme insulin resistance, which disrupts normal growth and development from the early stages of life. Associated genes include INSR.

← Back to All Diseases

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

Donohue 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

Donohue 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 Donohue syndrome?

What are the symptoms of Donohue syndrome?

What causes Donohue syndrome?

How is Donohue syndrome inherited?

How rare is Donohue syndrome?

How is Donohue syndrome diagnosed?

Are there treatments for Donohue syndrome?

What are the specific growth challenges faced by individuals with Donohue syndrome?

How does Donohue syndrome affect daily life for those who have it?

What is the life expectancy for someone with Donohue syndrome?

Are there any specialists recommended for managing Donohue 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