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lateral meningocele syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

lateral meningocele syndrome

MONDO:0007537

Also known as:Lehman syndromeLMNSLms

Find Clinical TrialsTrials

Overview

GeneticsAutosomal dominant · NOTCH3 (chr 19)

Clinical Trials1 registered · 1 recruiting

ResearchLimited published research (7 articles)

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: Hypernasal speech and Coarse hair; and very common findings: Posteriorly rotated ears, Downslanted palpebral fissures, Dural ectasia, and Conductive hearing impairment and others. 66 total HPO annotations.

Organ System	Phenotype Count	Example Features
Bones and joints	8	Joint hypermobility, Vertebral fusion, Biconcave vertebral bodies

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.

NOTCH3 encodes notch receptor 3 (2,321 aa). Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Highest expression in Artery Tibial (402.5 TPM) and Artery Aorta (222.4 TPM).

Lateral meningocele syndrome is associated with mutations in the NOTCH3 gene on chromosome 19.

The NOTCH3 protein participates in FRINGE-modified NOTCH3 Extracellular fragment (NECD3) and FRINGE-modified NOTCH3 Extracellular Fragment (NECD3) pathways.

NOTCH3 is classified as a druggable target (Cell Surface, Clinically Actionable, and Druggable Genome categories) with score 20.9.

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

Formal diagnostic clinical criteria for NOTCH3-related lateral meningocele syndrome (LMS) have not been established.

Suggestive Findings

NOTCH3-related LMS should be suspected in individuals with the following findings. Multiple lateral spinal meningoceles (protrusion of the arachnoid and dura through the spinal foramina) are present in all affected individuals. Characteristic craniofacial appearance includes widely spaced eyes, highly arched eyebrows, downslanted palpebral fissures, ptosis, malar flattening, long philtrum, thin vermilion of the upper lip, high and narrow palate, micrognathia, and coarse hair with a low posterior hairline. Additional findings that may be present:

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 lateral meningocele syndrome. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for NOTCH3-related lateral meningocele syndrome have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with NOTCH3-related lateral meningocele syndrome (LMS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with NOTCH3-Related Lateral Meningocele Syndrome (LMS)

Prognosis

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

GeneReviews

Surveillance Guidelines

There are no established surveillance guidelines for lateral spinal meningoceles. Close clinical and radiographic monitoring is recommended for progressive neurologic symptoms and meningocele size enlargement . MRI of the spine can be considered at a one- to two-year interval; an initial yearly scan to monitor for stability and subsequent spacing to every two years if meningoceles are small in size has been suggested. Larger lesions may require closer follow up [JA Cuoco 2022, personal communication]. Ongoing monitoring by the appropriate subspecialists for developmental, musculoskeletal, cardiovascular, genitourinary, gastrointestinal, ophthalmologic, and/or hearing issues is indicated.

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.

1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.

7 publications have been identified in PubMed for lateral meningocele syndrome. Research spans Case Report / Case Series (86%) and Gene Therapy / Novel Therapeutics (14%).

Recent Publications

Canalis E (2025). [PMID: 39752389](https://pubmed.ncbi.nlm.nih.gov/39752389/). *PloS one*. [Case Report / Case Series]
Ali R (2025). [PMID: 41079812](https://pubmed.ncbi.nlm.nih.gov/41079812/). *Clinical case reports*. [Case Report / Case Series]
Hayashi Y (2025). [PMID: 41432782](https://pubmed.ncbi.nlm.nih.gov/41432782/). *Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery*. [Gene Therapy / Novel Therapeutics]
Woods E (2025). [PMID: 40256810](https://pubmed.ncbi.nlm.nih.gov/40256810/). *American journal of medical genetics. Part A*. [Case Report / Case Series]
Pasa ID (2025). [PMID: 40771185](https://pubmed.ncbi.nlm.nih.gov/40771185/). *Molecular syndromology*. [Case Report / Case Series]

Data assembled from 8 of 12 sources · Last updated Sep 19, 2026, 9:42 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:130720

Orphanet

European rare disease database

Orphanet:2789

GARD

Genetic and Rare Diseases Info Center

GARD:9873

Questions for Your Care Team

→Are any of the 1 active clinical trial a good fit for my situation?
→Should I pursue genetic testing for NOTCH3, and what would the results mean for my family?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

The differential diagnosis for NOTCH3-related lateral meningocele syndrome (LMS) is summarized in . Table 4. Genes and Disorders of Interest in the Differential Diagnosis of NOTCH3-Related Lateral Meningocele Syndrome (LMS)

Gene(s)	Disorder	MOI	Key Features /Comment
BRAF, KRAS, LZTR1, MAP2K1, MRAS, NRAS, PTPN11, RAF1, RASA2, RIT1, RRAS2, SOS1, SOS2	Noonan syndrome (NS)	AD(AR)1	NOTCH3-related LMS NS share similarities in their characteristic facial features (incl widely spaced eyes, ptosis, epicanthus, low-set ears w/ posterior angulation) a low posterior hairline. Prenatal signs of NS (e.g.
FBN1	Marfan syndrome (MFS)	AD	NOTCH3-related LMS has significant overlap w/other connective tissue disorders. Spinal meningeal anomalies, specifically dural ectasias, are frequently seen in MFS. Persons w/MFS may also have joint laxity, scoliosis, cardiovascular anomalies, some shared facial features (e.g.
NF1	Neurofibromatosis type 1 (NF1)	AD	Lateral meningoceles dural ectasia have been described in some persons w/NF1.3 The distinctive facial features of NOTCH3-related LMS are not seen in persons w/NF1; other distinctive characteristics of NF1 incl caf au lait spots, neurofibromas, Lisch nodules.
NOTCH2	Hadju-Cheney syndrome (OMIM 102500)	AD	Skeletal disorder characterized by dysmorphic facial features (e.g., malar flattening, thick eyebrows, micrognathia), osteoporosis w/acro-osteolysis, wormian bones, premature loss of dentition, joint laxity.
FKBP14, PLOD1	FKBP14- PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (kEDS)	AR	Lateral meningocele has been described in 1 person w/kEDS, dural ectasia in at least 2 persons.5 Persons w/kEDS also present w/joint hypermobility, congenital hypotonia, progressive scoliosis kyphosis, motor delays, hyperextensibility of the skin.
SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, TGFBR2	Loeys-Dietz syndrome (LDS)	AD	Overlapping features in LDS NOTCH3-related LMS incl spinal pathology (dural ectasia in LDS), some facial features (e.g. downslanted palpebral fissures, proptosis, high arched palate), congenital heart defects, joint hypermobility, spine deformities.

Source: GeneReviews — "NOTCH3-Related Lateral Meningocele Syndrome"

System/Concern	Evaluation	Comment
neurologic issues	Neurologic eval	Assess for neuropathy, pain, neurogenic bladder /or paraparesis. Brain MRI
delay	Developmental assessment	To incl motor, adaptive, cognitive, speech-language eval; Eval for early intervention/ special education
Musculoskeletal	Assessment for abdominal hernia, ligamentous laxity/ joint concerns, scoliosis	—
Cardiovascular	Eval w/cardiologist to incl echocardiogram	—
Genitourinary	Assessment for cryptorchidism	—
Gastrointestinal	Infant feeding eval	Assess for GERD any palate abnormalities.
Eyes	Ophthalmologic eval	Assess for vision, abnormal ocular mvmt, structural eye abnormality.
Hearing	Audiologic eval	Assess for hearing loss. Genetic
counseling	By genetics professionals1	To inform affected persons their families re nature, MOI, implications of NOTCH3-related LMS in order to facilitate medical personal decision making Family support resources
Treatment of Manifestations in Individuals with NOTCH3-Related Lateral Meningocele Syndrome (LMS) Manifestation/Concern	Treatment	Considerations/Other Lateral spinal meningoceles; Symptomatic treatment of neurologic sequel (e.g., neurogenic bladder, paresthesias, back pain, /or paraparesis) as needed
delay	Timely supportive interventions as needed to optimize development through OT education resources	Musculoskeletal issues

Kisho

lateral meningocele syndrome

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

lateral meningocele syndrome

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

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

Clinical Guidance

Explore clinical features

Clinical Guidance

Penetrance

Differential Diagnosis

Therapies Under Investigation

Clinical Trials