Hereditary Neuropathy with Liability to Pressure Palsies

Mendelian MONDO:0008087 Pathograph 3 Genetic Disease Peripheral Neuropathy

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant PMP22-related peripheral neuropathy characterized by recurrent focal sensory and motor neuropathies after minor compression or stretch. The core mechanism is PMP22 dosage reduction in Schwann cells, usually from the recurrent 17p11.2-p12 deletion, which destabilizes compact myelin and makes entrapment-prone nerves vulnerable to conduction failure and tomaculous remodeling.

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👪

Inheritance

Autosomal dominant HP:0000006

Autosomal dominant inheritance

Show evidence (1 reference)

PMID:8393091 SUPPORT Human Clinical

"The hereditary transmission is autosomal dominant with total penetration but variable expression."

Family-based clinical study directly supports autosomal dominant inheritance for HNPP.

⚙

Pathophysiology

PMP22 Haploinsufficiency and Junctional Myelin Instability

Heterozygous PMP22 deletion or loss-of-function variation lowers PMP22 dosage in Schwann cells. Reduced PMP22 destabilizes tight and adherens junction architecture within compact peripheral myelin, increasing myelin permeability and making nerves unusually susceptible to mechanical compression.

Schwann cell link

PMP22 link

myelination in peripheral nervous system link ⚠ ABNORMAL cell junction assembly link ⚠ ABNORMAL

Downstream

Compression-Sensitive Conduction Failure Unstable myelin becomes vulnerable to brief pressure or stretch, leading to focal conduction slowing or block at entrapment sites.

Show evidence (2 references)

PMID:8422677 SUPPORT Human Clinical

"The deleted region appears uniform in all pedigrees and includes the gene for peripheral myelin protein 22 (PMP-22), suggesting that underexpression of PMP-22 may cause HNPP."

Human pedigree data identify PMP22 dosage loss as the initiating pathogenic mechanism in HNPP.

PMID:24339129 SUPPORT Model Organism

"We show disruption of multiple types of cell junction complexes in peripheral nerve, resulting in increased permeability of myelin and impaired action potential propagation."

Mouse-model work directly supports the junctional-myelin permeability mechanism downstream of PMP22 deficiency.

Compression-Sensitive Conduction Failure

Peripheral nerves exposed to ordinary entrapment sites develop recurrent focal sensory and motor neuropathies. Electrodiagnostic testing typically shows focal conduction abnormalities at compression sites, and some patients also show a mild generalized sensorimotor polyneuropathy.

Schwann cell link motor neuron link sensory neuron link

neuronal action potential propagation link ⚠ ABNORMAL

Show evidence (2 references)

PMID:30989370 SUPPORT Human Clinical

"Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by recurrent sensory and motor neuropathy in individual nerves starting in adolescence or young adulthood, focal conduction abnormalities at entrapment sites on nerve conduction studies, and sausage-like swellings..."

This review captures the clinically defining compression-sensitive, focal-conduction phenotype of HNPP.

PMID:24339129 SUPPORT Model Organism

"Our study reveals a novel mechanism by which PMP22 deficiency affects nerve conduction not through removal of myelin, but through disruption of myelin junctions."

This supports conduction failure as a functional consequence of PMP22 deficiency even before overt demyelination.

Tomaculous Myelin Remodeling

Schwann-cell myelin shows focal sausage-like thickenings (tomacula), a characteristic morphologic signature of unstable myelin maintenance in HNPP. These lesions can be present even in affected individuals without obvious prior pressure palsies.

Schwann cell link

myelination link ⚠ ABNORMAL

Show evidence (1 reference)

PMID:8393091 SUPPORT Human Clinical

"Large focal myelin thickenings (tomacula) were found in nerve biopsies of affected persons, whether or not pressure palsies had occurred."

Human nerve-biopsy data support tomacula as a characteristic morphologic lesion in HNPP.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

Musculoskeletal 1

Focal muscle weakness Muscle weakness (HP:0001324)

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"The most common initial manifestation is the acute onset of a non-painful focal sensory and motor neuropathy in a single nerve (mononeuropathy)."

The cited description directly supports focal motor weakness as part of the acute palsy phenotype.

Nervous System 3

Recurrent focal neuropathy Peripheral neuropathy (HP:0009830)

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by recurrent acute sensory and motor neuropathy in a single or multiple nerves."

GeneReviews defines recurrent focal neuropathy as the core human manifestation of HNPP.

Paresthesia Paresthesia (HP:0003401)

Chronic peripheral neuropathy Peripheral neuropathy (HP:0009830)

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Some affected individuals also demonstrate a mild-to-moderate peripheral neuropathy."

GeneReviews supports the broader chronic neuropathy component that can coexist with focal episodes.

🧬

Genetic Associations

PMP22 deletion or pathogenic variant (Causal deletion or pathogenic variant leading to PMP22 haploinsufficiency)

Show evidence (3 references)

PMID:20301566 SUPPORT Human Clinical

"The diagnosis of HNPP is established in a proband with suggestive clinical and electrophysiologic findings and either the 1.5-Mb recurrent deletion or a novel deletion involving PMP22 (in 80%), or a PMP22 sequence variant (in 20%) identified by molecular genetic testing."

GeneReviews summarizes the causal PMP22 lesion spectrum underlying HNPP.

PMID:8422677 SUPPORT Human Clinical

"The deletion in HNPP spans approximately 1.5 Mb and includes all markers that are known to map within the Charcot-Marie-Tooth neuropathy type 1A (CMT1A) duplication."

This original mapping study establishes the recurrent deletion architecture of classic HNPP.

CGGV:assertion_a7502a7e-2a4e-4b85-8f7c-8d76fe94f294-2024-07-08T160000.000Z SUPPORT Other

ClinGen classifies the PMP22-hereditary neuropathy with liability to pressure palsies gene-disease relationship as definitive with autosomal dominant inheritance.

💊

Treatments

Physical therapy

Action: physical therapy MAXO:0000011

Physical therapy is used symptomatically to support gross motor recovery, strength, gait safety, and daily function after focal neuropathic episodes.

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Treatment is symptomatic and involves occupational therapy and physical therapy as needed to address issues with fine motor and gross motor skills, including activities of daily living."

GeneReviews supports physical therapy as part of standard symptomatic management.

Occupational therapy

Action: occupational therapy MAXO:0001351

Occupational therapy is used for fine motor recovery, hand function, and activities of daily living, especially after upper-limb entrapment neuropathies.

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Treatment is symptomatic and involves occupational therapy and physical therapy as needed to address issues with fine motor and gross motor skills, including activities of daily living."

GeneReviews supports occupational therapy for upper-extremity function and daily living tasks.

Bracing and orthotic support

Action: orthotic device usage MAXO:0000482

Wrist splints and ankle-foot orthoses are used when focal weakness such as hand weakness or foot drop needs transient or ongoing mechanical support.

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Bracing, such as with a wrist splint or ankle-foot orthosis, may be useful transiently or in some instances permanently."

GeneReviews explicitly supports bracing and orthotic use in symptomatic HNPP management.

Analgesic pharmacotherapy for neuropathic pain

Action: Pharmacotherapy NCIT:C15986

No disease-modifying drug therapy is established; when neuropathic pain is present, symptomatic analgesic medication can be used.

Show evidence (1 reference)

PMID:20301566 SUPPORT Human Clinical

"Neuropathic pain can be treated with analgesic medications."

This supports drug-based symptomatic treatment of neuropathic pain in HNPP.

Compression protection and vincristine avoidance

Action: supportive care MAXO:0000950

Preventive management includes padding vulnerable compression sites, avoiding repetitive or prolonged nerve compression, and avoiding vincristine because it can worsen neuropathy.

Show evidence (2 references)

PMID:20301566 SUPPORT Human Clinical

"Protective pads at elbows or knees may prevent pressure and trauma to local nerves."

GeneReviews supports mechanical pressure protection as a practical recurrence-prevention strategy.

PMID:20301566 SUPPORT Human Clinical

"Agents/circumstances to avoid: Prolonged sitting with legs crossed; prolonged leaning on elbows; occupations requiring repetitive movements of the wrist; rapid weight loss; vincristine."

This provides clinically actionable trigger avoidance guidance, including the key drug-safety point to avoid vincristine.

{ }

Source YAML

click to show

name: Hereditary Neuropathy with Liability to Pressure Palsies
creation_date: '2026-04-21T04:40:35Z'
updated_date: '2026-05-09T17:39:56Z'
category: Mendelian
parents:
- Genetic Disease
- Peripheral Neuropathy
disease_term:
  preferred_term: hereditary neuropathy with liability to pressure palsies
  term:
    id: MONDO:0008087
    label: hereditary neuropathy with liability to pressure palsies
description: >-
  Hereditary neuropathy with liability to pressure palsies (HNPP) is an
  autosomal dominant PMP22-related peripheral neuropathy characterized by
  recurrent focal sensory and motor neuropathies after minor compression or
  stretch. The core mechanism is PMP22 dosage reduction in Schwann cells,
  usually from the recurrent 17p11.2-p12 deletion, which destabilizes compact
  myelin and makes entrapment-prone nerves vulnerable to conduction failure and
  tomaculous remodeling.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:8393091
    reference_title: >-
      Hereditary neuropathy with liability to pressure palsies: a clinical,
      electroneurophysiological and morphological study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The hereditary transmission is autosomal dominant with total penetration
      but variable expression.
    explanation: >-
      Family-based clinical study directly supports autosomal dominant
      inheritance for HNPP.
pathophysiology:
- name: PMP22 Haploinsufficiency and Junctional Myelin Instability
  description: >-
    Heterozygous PMP22 deletion or loss-of-function variation lowers PMP22
    dosage in Schwann cells. Reduced PMP22 destabilizes tight and adherens
    junction architecture within compact peripheral myelin, increasing myelin
    permeability and making nerves unusually susceptible to mechanical
    compression.
  genes:
  - preferred_term: PMP22
    term:
      id: hgnc:9118
      label: PMP22
  cell_types:
  - preferred_term: Schwann cell
    term:
      id: CL:0002573
      label: Schwann cell
  biological_processes:
  - preferred_term: myelination in peripheral nervous system
    modifier: ABNORMAL
    term:
      id: GO:0022011
      label: myelination in peripheral nervous system
  - preferred_term: cell junction assembly
    modifier: ABNORMAL
    term:
      id: GO:0034329
      label: cell junction assembly
  downstream:
  - target: Compression-Sensitive Conduction Failure
    description: >-
      Unstable myelin becomes vulnerable to brief pressure or stretch, leading
      to focal conduction slowing or block at entrapment sites.
  evidence:
  - reference: PMID:8422677
    reference_title: >-
      DNA deletion associated with hereditary neuropathy with liability to
      pressure palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The deleted region appears uniform in all pedigrees and includes the gene
      for peripheral myelin protein 22 (PMP-22), suggesting that underexpression
      of PMP-22 may cause HNPP.
    explanation: >-
      Human pedigree data identify PMP22 dosage loss as the initiating
      pathogenic mechanism in HNPP.
  - reference: PMID:24339129
    reference_title: Abnormal junctions and permeability of myelin in PMP22-deficient nerves.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      We show disruption of multiple types of cell junction complexes in
      peripheral nerve, resulting in increased permeability of myelin and
      impaired action potential propagation.
    explanation: >-
      Mouse-model work directly supports the junctional-myelin permeability
      mechanism downstream of PMP22 deficiency.
- name: Compression-Sensitive Conduction Failure
  description: >-
    Peripheral nerves exposed to ordinary entrapment sites develop recurrent
    focal sensory and motor neuropathies. Electrodiagnostic testing typically
    shows focal conduction abnormalities at compression sites, and some patients
    also show a mild generalized sensorimotor polyneuropathy.
  cell_types:
  - preferred_term: Schwann cell
    term:
      id: CL:0002573
      label: Schwann cell
  - preferred_term: motor neuron
    term:
      id: CL:0000100
      label: motor neuron
  - preferred_term: sensory neuron
    term:
      id: CL:0000101
      label: sensory neuron
  biological_processes:
  - preferred_term: neuronal action potential propagation
    modifier: ABNORMAL
    term:
      id: GO:0019227
      label: neuronal action potential propagation
  evidence:
  - reference: PMID:30989370
    reference_title: Hereditary neuropathy with liability to pressure palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Hereditary neuropathy with liability to pressure palsies (HNPP) is
      characterized by recurrent sensory and motor neuropathy in individual
      nerves starting in adolescence or young adulthood, focal conduction
      abnormalities at entrapment sites on nerve conduction studies, and
      sausage-like swellings (tomacula) of the myelin sheaths by nerve biopsy.
    explanation: >-
      This review captures the clinically defining compression-sensitive,
      focal-conduction phenotype of HNPP.
  - reference: PMID:24339129
    reference_title: Abnormal junctions and permeability of myelin in PMP22-deficient nerves.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Our study reveals a novel mechanism by which PMP22 deficiency affects
      nerve conduction not through removal of myelin, but through disruption of
      myelin junctions.
    explanation: >-
      This supports conduction failure as a functional consequence of PMP22
      deficiency even before overt demyelination.
- name: Tomaculous Myelin Remodeling
  description: >-
    Schwann-cell myelin shows focal sausage-like thickenings (tomacula), a
    characteristic morphologic signature of unstable myelin maintenance in HNPP.
    These lesions can be present even in affected individuals without obvious
    prior pressure palsies.
  cell_types:
  - preferred_term: Schwann cell
    term:
      id: CL:0002573
      label: Schwann cell
  biological_processes:
  - preferred_term: myelination
    modifier: ABNORMAL
    term:
      id: GO:0042552
      label: myelination
  evidence:
  - reference: PMID:8393091
    reference_title: >-
      Hereditary neuropathy with liability to pressure palsies: a clinical,
      electroneurophysiological and morphological study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Large focal myelin thickenings (tomacula) were found in nerve biopsies of
      affected persons, whether or not pressure palsies had occurred.
    explanation: >-
      Human nerve-biopsy data support tomacula as a characteristic morphologic
      lesion in HNPP.
phenotypes:
- category: Neurologic
  name: Recurrent focal neuropathy
  description: >-
    Recurrent acute sensory and motor neuropathy affecting single or multiple
    nerves, often after minor compression, is the typical presenting
    manifestation.
  diagnostic: true
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Hereditary neuropathy with liability to pressure palsies (HNPP) is
      characterized by recurrent acute sensory and motor neuropathy in a single
      or multiple nerves.
    explanation: >-
      GeneReviews defines recurrent focal neuropathy as the core human
      manifestation of HNPP.
- category: Neurologic
  name: Focal muscle weakness
  description: >-
    Motor deficits occur in the distribution of affected nerves during pressure
    palsies and may leave mild residual weakness if recovery is incomplete.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common initial manifestation is the acute onset of a non-painful
      focal sensory and motor neuropathy in a single nerve (mononeuropathy).
    explanation: >-
      The cited description directly supports focal motor weakness as part of
      the acute palsy phenotype.
- category: Neurologic
  name: Paresthesia
  description: >-
    Numbness and tingling commonly accompany focal sensory nerve involvement in
    affected limbs.
  phenotype_term:
    preferred_term: Paresthesia
    term:
      id: HP:0003401
      label: Paresthesia
- category: Neurologic
  name: Chronic peripheral neuropathy
  description: >-
    Beyond episodic pressure palsies, some individuals develop a mild-to-
    moderate background peripheral neuropathy.
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Some affected individuals also demonstrate a mild-to-moderate peripheral
      neuropathy.
    explanation: >-
      GeneReviews supports the broader chronic neuropathy component that can
      coexist with focal episodes.
biochemical: []
genetic:
- name: PMP22 deletion or pathogenic variant
  gene_term:
    preferred_term: PMP22
    term:
      id: hgnc:9118
      label: PMP22
  association: Causal deletion or pathogenic variant leading to PMP22 haploinsufficiency
  notes: >-
    Most affected individuals have the recurrent 1.5-Mb deletion involving
    PMP22; a minority have smaller PMP22 deletions or sequence variants with a
    similar loss-of-function effect.
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of HNPP is established in a proband with suggestive
      clinical and electrophysiologic findings and either the 1.5-Mb recurrent
      deletion or a novel deletion involving PMP22 (in 80%), or a PMP22
      sequence variant (in 20%) identified by molecular genetic testing.
    explanation: >-
      GeneReviews summarizes the causal PMP22 lesion spectrum underlying HNPP.
  - reference: PMID:8422677
    reference_title: >-
      DNA deletion associated with hereditary neuropathy with liability to
      pressure palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The deletion in HNPP spans approximately 1.5 Mb and includes all markers
      that are known to map within the Charcot-Marie-Tooth neuropathy type 1A
      (CMT1A) duplication.
    explanation: >-
      This original mapping study establishes the recurrent deletion architecture
      of classic HNPP.
  - reference: CGGV:assertion_a7502a7e-2a4e-4b85-8f7c-8d76fe94f294-2024-07-08T160000.000Z
    reference_title: "PMP22 / hereditary neuropathy with liability to pressure palsies (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "PMP22 | HGNC:9118 | hereditary neuropathy with liability to pressure palsies | MONDO:0008087 | AD | Definitive"
    explanation: ClinGen classifies the PMP22-hereditary neuropathy with liability to pressure palsies gene-disease relationship as definitive with autosomal dominant inheritance.
environmental: []
treatments:
- name: Physical therapy
  description: >-
    Physical therapy is used symptomatically to support gross motor recovery,
    strength, gait safety, and daily function after focal neuropathic episodes.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment is symptomatic and involves occupational therapy and physical
      therapy as needed to address issues with fine motor and gross motor
      skills, including activities of daily living.
    explanation: >-
      GeneReviews supports physical therapy as part of standard symptomatic
      management.
- name: Occupational therapy
  description: >-
    Occupational therapy is used for fine motor recovery, hand function, and
    activities of daily living, especially after upper-limb entrapment
    neuropathies.
  treatment_term:
    preferred_term: occupational therapy
    term:
      id: MAXO:0001351
      label: occupational therapy
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment is symptomatic and involves occupational therapy and physical
      therapy as needed to address issues with fine motor and gross motor
      skills, including activities of daily living.
    explanation: >-
      GeneReviews supports occupational therapy for upper-extremity function and
      daily living tasks.
- name: Bracing and orthotic support
  description: >-
    Wrist splints and ankle-foot orthoses are used when focal weakness such as
    hand weakness or foot drop needs transient or ongoing mechanical support.
  treatment_term:
    preferred_term: orthotic device usage
    term:
      id: MAXO:0000482
      label: orthotic device usage
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bracing, such as with a wrist splint or ankle-foot orthosis, may be
      useful transiently or in some instances permanently.
    explanation: >-
      GeneReviews explicitly supports bracing and orthotic use in symptomatic
      HNPP management.
- name: Analgesic pharmacotherapy for neuropathic pain
  description: >-
    No disease-modifying drug therapy is established; when neuropathic pain is
    present, symptomatic analgesic medication can be used.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neuropathic pain can be treated with analgesic medications.
    explanation: >-
      This supports drug-based symptomatic treatment of neuropathic pain in
      HNPP.
- name: Compression protection and vincristine avoidance
  description: >-
    Preventive management includes padding vulnerable compression sites,
    avoiding repetitive or prolonged nerve compression, and avoiding
    vincristine because it can worsen neuropathy.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Protective pads at elbows or knees may prevent pressure and trauma to
      local nerves.
    explanation: >-
      GeneReviews supports mechanical pressure protection as a practical
      recurrence-prevention strategy.
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Agents/circumstances to avoid: Prolonged sitting with legs crossed;
      prolonged leaning on elbows; occupations requiring repetitive movements of
      the wrist; rapid weight loss; vincristine.
    explanation: >-
      This provides clinically actionable trigger avoidance guidance, including
      the key drug-safety point to avoid vincristine.
diagnosis:
- name: Nerve conduction studies
  description: >-
    Electrodiagnostic testing identifies focal entrapment-site abnormalities
    and can reveal the broader sensorimotor neuropathy pattern even when the
    history is atypical.
  diagnosis_term:
    preferred_term: nerve conduction study
    term:
      id: MAXO:0035059
      label: nerve conduction study
  results: Focal conduction abnormalities or delayed sensorimotor latencies support HNPP.
  evidence:
  - reference: PMID:12827539
    reference_title: >-
      Hereditary neuropathy with liability to pressure palsies:
      electrophysiological and genetic study of a family with carpal tunnel
      syndrome as only clinical manifestation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Electrophysiological examination is of great importance for the diagnosis
      of HNPP.
    explanation: >-
      This directly supports nerve conduction studies as a core diagnostic test,
      especially in atypical presentations.
- name: PMP22 molecular genetic testing
  description: >-
    Deletion/duplication analysis plus sequence analysis of PMP22 confirms the
    diagnosis and can distinguish classic recurrent deletion HNPP from
    non-deletion PMP22-related disease.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
  results: A recurrent PMP22 deletion, other PMP22 deletion, or pathogenic PMP22 sequence variant establishes HNPP.
  evidence:
  - reference: PMID:20301566
    reference_title: Hereditary Neuropathy with Liability to Pressure Palsies.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis of HNPP is established in a proband with suggestive
      clinical and electrophysiologic findings and either the 1.5-Mb recurrent
      deletion or a novel deletion involving PMP22 (in 80%), or a PMP22
      sequence variant (in 20%) identified by molecular genetic testing.
    explanation: >-
      GeneReviews directly supports molecular confirmation through PMP22 testing.
  - reference: PMID:12827539
    reference_title: >-
      Hereditary neuropathy with liability to pressure palsies:
      electrophysiological and genetic study of a family with carpal tunnel
      syndrome as only clinical manifestation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Genetic analysis is a rapid and reliable diagnostic tool that can be
      combined with simplified electrophysiological examination, avoiding the
      need for nerve biopsy.
    explanation: >-
      This supports practical clinical use of genetic testing in the diagnostic
      workflow.
clinical_trials: []
datasets: []
references:
- reference: PMID:20301566
  title: "Hereditary Neuropathy with Liability to Pressure Palsies."
  tags:
  - GeneReviews
  findings: []
- reference: DOI:10.1007/s00415-024-12839-7
  title: Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies
    supporting_text: Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies
- reference: DOI:10.1007/s12035-012-8370-x
  title: The PMP22 Gene and Its Related Diseases
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: The PMP22 Gene and Its Related Diseases
    supporting_text: The PMP22 Gene and Its Related Diseases
- reference: DOI:10.1093/brain/awae064
  title: Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes.
    supporting_text: Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes.
    evidence:
    - reference: DOI:10.1093/brain/awae064
      reference_title: Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes.
      explanation: Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.
- reference: DOI:10.1093/hmg/ddaa082
  title: Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy.
    supporting_text: Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy.
    evidence:
    - reference: DOI:10.1093/hmg/ddaa082
      reference_title: Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy.
      explanation: Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.
- reference: DOI:10.1186/1750-1172-9-38
  title: 'PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies'
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: 'PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies'
    supporting_text: 'PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies'
- reference: DOI:10.3389/fgene.2025.1613022
  title: 'Case Report: Hereditary neuropathy with liability to pressure palsy (HNPP): the role of genetic investigation in diagnostic assessment'
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression.
    supporting_text: Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression.
    evidence:
    - reference: DOI:10.3389/fgene.2025.1613022
      reference_title: 'Case Report: Hereditary neuropathy with liability to pressure palsy (HNPP): the role of genetic investigation in diagnostic assessment'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression.
      explanation: Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.
- reference: DOI:10.3390/genes16111279
  title: 'PMP22-Related Neuropathies: A Systematic Review'
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: 'PMP22-Related Neuropathies: A Systematic Review'
    supporting_text: PMP22-related neuropathies comprise a spectrum of predominantly demyelinating disorders, most commonly Charcot–Marie–Tooth type 1A (CMT1A; 17p12 duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; 17p12 deletion), with rarer phenotypes due to PMP22 sequence variants (CMT1E, Dejerine–Sottas syndrome [DSS]).
    evidence:
    - reference: DOI:10.3390/genes16111279
      reference_title: 'PMP22-Related Neuropathies: A Systematic Review'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: PMP22-related neuropathies comprise a spectrum of predominantly demyelinating disorders, most commonly Charcot–Marie–Tooth type 1A (CMT1A; 17p12 duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; 17p12 deletion), with rarer phenotypes due to PMP22 sequence variants (CMT1E, Dejerine–Sottas syndrome [DSS]).
      explanation: Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.
- reference: DOI:10.3390/healthcare12080858
  title: 'Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review'
  found_in:
  - Hereditary_Neuropathy_with_Liability_to_Pressure_Palsies-deep-research-falcon.md
  findings:
  - statement: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces.
    supporting_text: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces.
    evidence:
    - reference: DOI:10.3390/healthcare12080858
      reference_title: 'Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces.
      explanation: Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

📚

References & Deep Research

References

PMID:20301566

Hereditary Neuropathy with Liability to Pressure Palsies.

No top-level findings curated for this source.

DOI:10.1007/s00415-024-12839-7

Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies

1 finding

Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies

"Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies"

DOI:10.1007/s12035-012-8370-x

The PMP22 Gene and Its Related Diseases

1 finding

The PMP22 Gene and Its Related Diseases

"The PMP22 Gene and Its Related Diseases"

DOI:10.1093/brain/awae064

Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease

1 finding

Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes.

"Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes."

Show evidence (1 reference)

DOI:10.1093/brain/awae064 SUPPORT Human Clinical

"Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes."

Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

DOI:10.1093/hmg/ddaa082

Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves

1 finding

Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy.

"Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy."

Show evidence (1 reference)

DOI:10.1093/hmg/ddaa082 SUPPORT Human Clinical

"Copy number variation of the peripheral nerve myelin gene Peripheral Myelin Protein 22 (PMP22) causes multiple forms of inherited peripheral neuropathy."

Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

DOI:10.1186/1750-1172-9-38

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

1 finding

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

"PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies"

DOI:10.3389/fgene.2025.1613022

Case Report: Hereditary neuropathy with liability to pressure palsy (HNPP): the role of genetic investigation in diagnostic assessment

1 finding

Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression.

"Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression."

Show evidence (1 reference)

DOI:10.3389/fgene.2025.1613022 SUPPORT Human Clinical

"Hereditary neuropathy with liability to pressure palsies (HNPP) is a genetic disorder characterized by recurrent focal neuropathies typically occurring at sites of nerve entrapment or compression."

Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

DOI:10.3390/genes16111279

PMP22-Related Neuropathies: A Systematic Review

1 finding

PMP22-Related Neuropathies: A Systematic Review

"PMP22-related neuropathies comprise a spectrum of predominantly demyelinating disorders, most commonly Charcot–Marie–Tooth type 1A (CMT1A; 17p12 duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; 17p12 deletion), with rarer phenotypes due to PMP22 sequence variants..."

Show evidence (1 reference)

DOI:10.3390/genes16111279 SUPPORT Other

Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

DOI:10.3390/healthcare12080858

Anesthetic Considerations for Patients with Hereditary Neuropathy with Liability to Pressure Palsies: A Narrative Review

1 finding

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces.

"Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces."

Show evidence (1 reference)

DOI:10.3390/healthcare12080858 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Hereditary Neuropathy with Liability to Pressure Palsies.

Deep Research

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 24 citations 2026-05-09T09:20:43.008994

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: Hereditary Neuropathy with Liability to Pressure Palsies
MONDO ID: (if available)
Category: Mendelian

Research Objectives

Please provide a comprehensive research report on Hereditary Neuropathy with Liability to Pressure Palsies covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Comprehensive Research Report: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)

Executive summary (current understanding)

Hereditary neuropathy with liability to pressure palsies (HNPP) is a Mendelian, typically autosomal dominant, predominantly demyelinating peripheral neuropathy characterized by recurrent focal mononeuropathies precipitated by minor compression/traction/trauma at entrapment sites, with variable recovery and occasional persistent deficits. It is most commonly caused by a heterozygous recurrent ~1.4–1.5 Mb deletion at 17p11.2–p12 encompassing PMP22, producing PMP22 haploinsufficiency, abnormal myelin (tomacula/myelin overfolding), and susceptibility to pressure-induced conduction block. (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2)

1. Disease information

1.1 What is the disease?

Definition/overview. A recent perioperative-focused narrative review defines HNPP as an “autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces” (published April 2024; Healthcare; https://doi.org/10.3390/healthcare12080858). (laudanski2024anestheticconsiderationsfor pages 1-2)

An Orphanet-focused review describes the classic clinical phenotype as “episodic, painless, recurrent, focal motor and sensory peripheral neuropathy, preceded by minor compression on the affected nerve” (published March 2014; Orphanet Journal of Rare Diseases; https://doi.org/10.1186/1750-1172-9-38). (paassen2014pmp22relatedneuropathies pages 1-2)

1.2 Key identifiers (ontology/database cross-references)

MONDO: MONDO:0008087 (MONDO_0008087) (OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22)
Orphanet: ORPHA:640 (paassen2014pmp22relatedneuropathies pages 7-9)

Not retrieved in the current evidence set: OMIM number(s), ICD-10/ICD-11 codes, and MeSH descriptor IDs were not available from the retrieved sources and should be confirmed via OMIM/Orphanet/ICD/MeSH lookups during knowledge-base curation.

1.3 Synonyms and alternative names

Synonyms reported in peer-reviewed literature include: * Tomaculous neuropathy; familial recurrent polyneuropathy (Orphanet review) (paassen2014pmp22relatedneuropathies pages 7-9) * Historical term “potato grubbing disease” (case report; Aug 2025; Frontiers in Genetics; https://doi.org/10.3389/fgene.2025.1613022) (savasta2025casereporthereditary pages 1-2)

1.4 Evidence provenance (individual vs aggregated)

The information summarized here is derived from aggregated disease-level resources and published case/cohort literature (reviews, cohort diagnostic series, and mechanistic animal studies), rather than EHR-only sources. (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2, chen2025literaturereviewof pages 1-2)

2. Etiology

2.1 Disease causal factors (primary causes)

HNPP is primarily a genetic disease driven by PMP22 dosage reduction (haploinsufficiency): * The canonical lesion is a recurrent heterozygous ~1.4–1.5 Mb deletion in the 17p11.2–p12 region including PMP22. (paassen2014pmp22relatedneuropathies pages 7-9, fabrizi2015disordersofperipheral pages 7-9) * A minority of HNPP cases result from PMP22 sequence-level loss-of-function variants (e.g., truncating/null alleles). (li2013thepmp22gene pages 15-17, paassen2014pmp22relatedneuropathies pages 7-9)

A recent literature review summarizing cases from January 2003–June 2024 states: “Most patients with HNPP have a heterozygous deletion on chromosome 17p11.2, the region that encompasses the gene for peripheral myelin protein 22 (PMP22).” (Journal of Neurology; online 2024/print 2025; https://doi.org/10.1007/s00415-024-12839-7). (chen2025literaturereviewof pages 1-2)

2.2 Risk factors

Genetic risk factor (causal). Carrying the heterozygous 17p11.2–p12 deletion encompassing PMP22 is the principal causal risk factor. (paassen2014pmp22relatedneuropathies pages 7-9)

Environmental/mechanical triggers. Many episodes are precipitated by mechanical stressors (compression/traction/prolonged positioning), acting as trigger exposures in genetically susceptible nerves. (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 4-5)

2.3 Protective factors

No specific genetic or environmental protective factors were identified in the retrieved evidence set.

2.4 Gene–environment interactions

A clinically important G×E interaction is that PMP22 haploinsufficiency creates a vulnerable myelin architecture, such that ordinary mechanical exposures (compression/traction) can precipitate focal conduction failure/mononeuropathy episodes. (paassen2014pmp22relatedneuropathies pages 7-9, pantera2020pmp22superenhancerdeletion pages 4-7)

3. Phenotypes

3.1 Core clinical phenotype (signs/symptoms)

Typical manifestations include recurrent focal motor and sensory deficits in single-nerve distributions or plexus patterns, particularly at entrapment sites. Commonly affected nerves include peroneal/common fibular, ulnar, median, radial, and brachial plexus distributions. (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 4-5, chen2025literaturereviewof pages 1-2)

A 2024 review notes episodes may last “hours to months” and recurrence is common. (laudanski2024anestheticconsiderationsfor pages 1-2)

3.2 Phenotype frequencies and clinical heterogeneity (recent compiled case series)

A clinical literature review (cases assembled through June 2024) reported the following frequencies in 124 HNPP cases: * “Typical weakness and numbness in vulnerable areas” in 63.7% * 62% experienced recurrent episodes * Atypical symptoms in 29.8% * Asymptomatic in 6.5% * “Pain and muscular dystrophy” in 17.7% * Pes cavus in 12.1% * Family history in 64.5% * Triggers among symptomatic patients: traction or compression (57.8%), temperature changes (3.4%), unclear (38.8%). (chen2025literaturereviewof pages 1-2)

Pain as an under-recognized feature. A case report emphasizes that although HNPP is “classically described as a painless condition,” pain is “frequently reported,” and may represent an early feature in some individuals. (savasta2025casereporthereditary pages 1-2)

3.3 Suggested HPO terms (not exhaustive; based on reported clinical patterns)

Recurrent focal neuropathy / mononeuropathy: HP:0009830 (Peripheral neuropathy) (conceptual mapping)
Paresthesia: HP:0003401
Numbness: HP:0003401/HP:0003402 (conceptual; depending on ontology granularity)
Foot drop: HP:0001761
Muscle weakness: HP:0001324
Areflexia/hyporeflexia: HP:0001284
Pes cavus: HP:0001761 (note: HPO has HP:0001761 for foot drop; pes cavus is HP:0001761?—verify exact HPO IDs during curation)

Because HPO identifiers are not provided directly in the retrieved literature excerpts, these should be validated against the current HPO release before ingestion.

4. Genetic / molecular information

4.1 Causal genes

PMP22 (peripheral myelin protein 22) is the principal causal gene. (OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22, paassen2014pmp22relatedneuropathies pages 7-9)

4.2 Pathogenic variants (variant classes and frequencies)

Canonical CNV: recurrent heterozygous deletion spanning PMP22 (~1.4–1.5 Mb), responsible for the majority of HNPP cases (multiple reviews). (paassen2014pmp22relatedneuropathies pages 7-9, fabrizi2015disordersofperipheral pages 7-9)
Sequence variants: PMP22 truncating/null alleles and other variants can also cause HNPP; a mechanistic review of PMP22 disease biology states that many HNPP mutations are truncations and are “functionally equivalent to classical chromosome 17p11.2 deletion with loss of function of PMP22.” (li2013thepmp22gene pages 15-17)

Inheritance and penetrance. HNPP is autosomal dominant; a 2024 narrative review reports penetrance “70–100%,” and notes that “approximately 20% of cases” result from de novo deletions or point mutations. (laudanski2024anestheticconsiderationsfor pages 1-2)

4.3 Modifier genes / epigenetics

No specific modifier genes or epigenetic mechanisms for HNPP were identified in the retrieved evidence set.

4.4 Disease-target association (curated evidence)

OpenTargets links PMP22 to HNPP (MONDO_0008087) with multiple literature evidence items (e.g., PubMed IDs 9748013, 12796555, 15099592 in the OpenTargets evidence list). (OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22)

5. Environmental information

HNPP is not an infectious disease and is not primarily environmentally caused; however, mechanical exposures (compression, traction, shear forces, prolonged positioning) are major episode triggers in genetically affected individuals. (laudanski2024anestheticconsiderationsfor pages 4-5, laudanski2024anestheticconsiderationsfor pages 1-2)

6. Mechanism / pathophysiology

6.1 Causal chain (from genotype to clinical episodes)

Genetic lesion: PMP22 dosage reduction (typically 17p11.2–p12 deletion). (paassen2014pmp22relatedneuropathies pages 7-9)
Cell type: Schwann-cell myelin maintenance is compromised by PMP22 haploinsufficiency, producing focal myelin architectural abnormalities. (paassen2014pmp22relatedneuropathies pages 7-9)
Tissue-level hallmark: tomacula (myelin overfolding/focal thickenings) and related nodal/paranodal changes. (paassen2014pmp22relatedneuropathies pages 7-9)
Physiology: predisposition to pressure/stretch-induced reversible conduction block, clinically manifesting as recurrent focal palsies at entrapment sites. (paassen2014pmp22relatedneuropathies pages 7-9, fabrizi2015disordersofperipheral pages 7-9)

6.2 Primary mechanistic evidence (animal model; regulatory mechanism)

Pantera et al. (Human Molecular Genetics; April 2020; https://doi.org/10.1093/hmg/ddaa082) tested whether deleting a distal Pmp22 super-enhancer reduces expression and phenocopies HNPP. The abstract states that “the reciprocal deletion of this gene causes a separate neuropathy termed Hereditary Neuropathy with Liability to Pressure Palsies (HNPP),” and reports that super-enhancer deletion reduces Pmp22 expression and leads to “tomacula formed by excessive myelin folding, a pathological hallmark of HNPP.” (pantera2020pmp22superenhancerdeletion pages 1-2)

The same study reports functional vulnerability to mechanically induced conduction failure (compression assay) and impaired recovery in more severe genotypes, linking PMP22 transcriptional control to conduction block susceptibility. (pantera2020pmp22superenhancerdeletion pages 4-7)

Visual evidence. Cropped panels from this study show teased-fiber tomacula quantification and the mechanical compression assay demonstrating time-to-conduction-block and recovery curves. (pantera2020pmp22superenhancerdeletion media 04ee1ad6, pantera2020pmp22superenhancerdeletion media 85bcd5c7)

6.3 Suggested GO biological process terms (verify IDs during curation)

Schwann cell differentiation / myelination
Peripheral nervous system myelination
Axon ensheathment
Response to mechanical stimulus (contextual)

6.4 Suggested Cell Ontology (CL) terms (verify IDs during curation)

Schwann cell (myelinating Schwann cell)

6.5 Suggested UBERON anatomical terms

Peripheral nerve
Sciatic nerve (commonly studied in models)

7. Anatomical structures affected

7.1 Organ/system level

Primary system: Peripheral nervous system (peripheral nerves subject to entrapment/compression). (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 4-5)

7.2 Tissue/cell level

Tissue: peripheral myelin; nerve fascicles at entrapment sites.
Cell type: Schwann cells. (pantera2020pmp22superenhancerdeletion pages 1-2, paassen2014pmp22relatedneuropathies pages 7-9)

7.3 Subcellular level

No specific subcellular compartment signature for HNPP was identified in the retrieved evidence set.

8. Temporal development (natural history)

8.1 Onset

Typical onset is often in the 2nd–3rd decade, but a wide age range is reported. (paassen2014pmp22relatedneuropathies pages 7-9, chen2025literaturereviewof pages 1-2)

8.2 Course/progression

The course is often episodic with recurrent focal palsies and variable recovery. The perioperative-focused review notes that episodes usually resolve over “days to months” but persistent deficits can occur. (laudanski2024anestheticconsiderationsfor pages 4-5)

9. Inheritance and population

9.1 Inheritance pattern

Autosomal dominant inheritance is consistently reported. (paassen2014pmp22relatedneuropathies pages 1-2, savasta2025casereporthereditary pages 1-2)

9.2 Epidemiology (statistics)

Frequently cited prevalence/incidence estimates are ~7–16 per 100,000. (paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2)

Regional estimates include ~7.3/100,000 in England and ~16/100,000 in southwestern Finland. (paassen2014pmp22relatedneuropathies pages 7-9, lehtilahti2022charcotmarietoothdiseasemolecular pages 25-28)

Underdiagnosis and higher genetic prevalence signals. A 2024 narrative review notes that the reported incidence may be an underestimation due to underdiagnosis. (laudanski2024anestheticconsiderationsfor pages 1-2) A compiled literature review reports newborn-screening-based prevalence estimates up to 58.9/100,000, suggesting population prevalence may exceed clinically ascertained estimates. (chen2025literaturereviewof pages 1-2)

10. Diagnostics

10.1 Clinical/electrodiagnostic evaluation

Electrophysiology is central: characteristic findings include increased distal motor latencies, focal slowing at entrapment sites, and sensory nerve conduction abnormalities. (paassen2014pmp22relatedneuropathies pages 7-9, paassen2014pmp22relatedneuropathies pages 1-2)

A 2024 perioperative review summarizes a suggestive signature: bilateral median sensorimotor latency prolongation plus at least unilateral peroneal motor abnormality, and notes diminished/absent sural responses in ~one-third of patients. (laudanski2024anestheticconsiderationsfor pages 4-5)

10.2 Imaging

Nerve ultrasound and MRI (including diffusion tensor imaging) can provide supportive findings in some settings. (laudanski2024anestheticconsiderationsfor pages 4-5)

10.3 Genetic testing approach (real-world implementation)

First-line molecular test (typical workflow): assay for PMP22 deletion (copy number) using MLPA or chromosomal microarray, with confirmatory approaches including FISH or PCR-based methods depending on laboratory practice. (laudanski2024anestheticconsiderationsfor pages 4-5, cesaroni2025pmp22relatedneuropathiesa pages 13-15)

If deletion testing is negative or phenotype is atypical: sequence analysis of PMP22 and/or inherited neuropathy gene panels, WES, or WGS may be used to detect rarer sequence variants or alternative diagnoses. (cesaroni2025pmp22relatedneuropathiesa pages 15-17, record2024wholegenomesequencing pages 1-2)

2024 genomic diagnostics data (large specialist cohort). In a single inherited neuropathy center cohort (Brain; March 2024; https://doi.org/10.1093/brain/awae064), 1,515 patients with CMT and related disorders were studied; 72 were HNPP (4.8%), and “PMP22 deletion (HNPP; 72/1165, 6.2%)” represented a major solved diagnosis category. (record2024wholegenomesequencing pages 1-2)

The same study emphasizes pragmatic workflow: “it is essential to ensure MLPA for PMP22 CNV has been performed, before moving to NGS.” (record2024wholegenomesequencing pages 3-5)

10.4 Differential diagnosis

HNPP can be misdiagnosed as radiculopathy or focal chronic inflammatory demyelinating polyneuropathy (CIDP), among others, and recurrence plus supportive electrodiagnostics and genetic confirmation aid distinction. (savasta2025casereporthereditary pages 1-2)

11. Outcome / prognosis

Life expectancy is generally reported as normal in PMP22-related neuropathy reviews, and many episodes recover; however, persistent deficits may occur. (paassen2014pmp22relatedneuropathies pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)

Quantitative quality-of-life instrument results (e.g., SF-36/EQ-5D) were not available in the retrieved evidence set.

12. Treatment

12.1 Current standard management (real-world implementation)

There is no established disease-modifying pharmacotherapy for HNPP in the retrieved evidence set; management is mainly supportive and preventive: * Avoidance of compressive/traction triggers; ergonomic/occupational modifications. (laudanski2024anestheticconsiderationsfor pages 4-5) * Multidisciplinary rehabilitation (physiotherapy/occupational therapy) is described in PMP22-related neuropathy reviews. (paassen2014pmp22relatedneuropathies pages 1-2)

12.2 Perioperative/anesthesia precautions (2024 expert synthesis)

Because surgical positioning and anesthesia can impose prolonged compression/shear on nerves, perioperative teams are advised to implement tailored positioning/monitoring strategies for HNPP patients. (laudanski2024anestheticconsiderationsfor pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)

12.3 Procedures and symptomatic interventions

Entrapment neuropathies (e.g., carpal tunnel syndrome) in inherited neuropathy. A completed observational study used patient-reported outcomes to evaluate carpal tunnel therapies in adults with inherited neuropathy including HNPP (ClinicalTrials.gov NCT02788734; start June 2016; primary completion Nov 2016). Outcomes included Boston Carpal Tunnel Questionnaire (BCTQ) and DASH (Disabilities of the Arm, Shoulder and Hand). (NCT02788734 chunk 1)

12.4 MAXO term suggestions (verify IDs during curation)

Physical therapy; occupational therapy
Genetic counseling
Avoidance of mechanical nerve compression
Perioperative positioning precautions
Nerve decompression surgery (in selected entrapment neuropathies)

13. Prevention

Primary and tertiary prevention focus on reducing mechanical nerve injury risk: * Avoid prolonged pressure at bony prominences; protective padding and repositioning during sleep, work, and surgery. (laudanski2024anestheticconsiderationsfor pages 4-5) * Perioperative positioning protocols for known/suspected HNPP. (laudanski2024anestheticconsiderationsfor pages 1-2)

14. Other species / natural disease

No naturally occurring veterinary analogs were identified in the retrieved evidence set.

15. Model organisms

15.1 Mouse regulatory-element model phenocopying HNPP

Pantera et al. (2020) created mice with CRISPR deletion of a distal Pmp22 super-enhancer, demonstrating reduced Pmp22 expression, tomacula formation, and susceptibility to compression-induced conduction block, thereby modeling a regulatory mechanism for PMP22 haploinsufficiency phenotypes relevant to HNPP. (pantera2020pmp22superenhancerdeletion pages 1-2, pantera2020pmp22superenhancerdeletion pages 4-7)

Recent developments and “latest research” (prioritizing 2023–2024)

A. Precision diagnostics: WGS as a complement to traditional CNV testing (2024)

A 2024 Brain study from a specialist center reported a very high overall genetic diagnostic rate (76.9% overall in 1,515 CMT-related patients) and quantified the contribution of PMP22 deletion diagnoses (HNPP) in the solved cohort, while reporting a modest additional uplift attributable to WGS in their end-to-end pipeline. (record2024wholegenomesequencing pages 1-2, record2024wholegenomesequencing pages 3-5)

B. Perioperative risk management and implementation guidance (2024)

A 2024 narrative review synthesized contemporary evidence and recommendations for anesthesia/surgical teams, emphasizing that HNPP patients may be under-recognized perioperatively and benefit from tailored positioning and monitoring strategies. (laudanski2024anestheticconsiderationsfor pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)

C. Real-world registries capturing outcomes and heterogeneity

GRIN registry / natural history survey includes HNPP among inherited neuropathies in a large recruiting observational program (ClinicalTrials.gov NCT05902351, start 2013; estimated primary completion 2029). (NCT05902351 chunk 1)
Carpal tunnel PRO study in inherited neuropathies (ClinicalTrials.gov NCT02788734) included HNPP and used standardized PRO instruments, illustrating how patient-centered outcomes are being deployed in real-world inherited neuropathy populations. (NCT02788734 chunk 1)

Key evidence gaps for knowledge-base completion

OMIM/ICD/MeSH identifiers were not retrieved in the current evidence set.
Robust population-based carrier frequency/founder-effect data were not found in the retrieved corpus.
Quantitative QoL data using standardized instruments (EQ-5D/SF-36/PROMIS) were not found in retrieved excerpts.

Evidence summary table (knowledge-base scaffold)

Domain	Key fact	Details	Citation placeholder
Disease name	Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)	Mendelian inherited peripheral neuropathy characterized by recurrent focal pressure palsies/mononeuropathies	(paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2)
Identifiers	MONDO	MONDO:0008087	(OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22)
Identifiers	Orphanet	ORPHA:640	(paassen2014pmp22relatedneuropathies pages 7-9)
Synonyms	Common alternative names	Hereditary neuropathy with liability to pressure palsy; tomaculous neuropathy; familial recurrent polyneuropathy; historical term “potato grubbing disease”	(paassen2014pmp22relatedneuropathies pages 7-9, savasta2025casereporthereditary pages 1-2, fabrizi2015disordersofperipheral pages 7-9)
Information source type	Evidence provenance	Aggregated disease-level resources and published case/cohort literature; not primarily EHR-derived	(paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2, chen2025literaturereviewof pages 1-2)
Inheritance	Mode of inheritance	Autosomal dominant; offspring recurrence risk typically 50% for an affected heterozygous parent	(paassen2014pmp22relatedneuropathies pages 1-2, laudanski2024anestheticconsiderationsfor pages 1-2)
Inheritance	Penetrance / de novo	Penetrance reported ~70–100%; de novo events occur, estimated around 20% in some reviews	(laudanski2024anestheticconsiderationsfor pages 1-2, paassen2014pmp22relatedneuropathies pages 7-9)
Causal gene	Primary gene	PMP22 (peripheral myelin protein 22)	(OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22, paassen2014pmp22relatedneuropathies pages 7-9)
Causal lesion	Canonical pathogenic lesion	Recurrent heterozygous ~1.4–1.5 Mb deletion at 17p11.2/17p12 including PMP22; causes PMP22 haploinsufficiency	(paassen2014pmp22relatedneuropathies pages 7-9, fabrizi2015disordersofperipheral pages 7-9)
Causal lesion	Less common pathogenic variants	PMP22 sequence variants/small indels/splice variants can also cause HNPP; loss-of-function/null alleles are important	(cesaroni2025pmp22relatedneuropathiesa pages 12-13, li2013thepmp22gene pages 15-17, laudanski2024anestheticconsiderationsfor pages 4-5)
Mechanistic summary	Core disease mechanism	PMP22 dosage reduction in Schwann cells destabilizes peripheral myelin, producing tomacula/myelin overfolding and susceptibility to pressure-induced conduction block	(pantera2020pmp22superenhancerdeletion pages 1-2, pantera2020pmp22superenhancerdeletion pages 4-7, paassen2014pmp22relatedneuropathies pages 7-9)
Prevalence / incidence	Classic epidemiologic estimate	Frequently cited prevalence/incidence range: ~7–16 per 100,000	(laudanski2024anestheticconsiderationsfor pages 1-2, paassen2014pmp22relatedneuropathies pages 7-9)
Prevalence / incidence	Regional estimates	Approx. 7.3/100,000 in England and 16/100,000 in southwestern Finland	(paassen2014pmp22relatedneuropathies pages 7-9, lehtilahti2022charcotmarietoothdiseasemolecular pages 25-28)
Prevalence / incidence	Potential underdiagnosis / higher genomic estimate	Underdiagnosis is likely; newborn genetic screening data have suggested substantially higher prevalence, including ~58.9/100,000 and 1 in 1,698 in one report/reviewed literature	(chen2025literaturereviewof pages 1-2, savasta2025casereporthereditary pages 1-2)
Typical onset	Age at onset	Usually 2nd–3rd decade, but can range from childhood to late adulthood; mean onset in one 2025 review was 26.5 ± 18 years	(paassen2014pmp22relatedneuropathies pages 7-9, chen2025literaturereviewof pages 1-2)
Typical course	Clinical pattern	Episodic, recurrent, often painless focal motor and sensory neuropathies; recovery may occur over days to months, but residual deficits can persist	(paassen2014pmp22relatedneuropathies pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)
Typical triggers	Mechanical triggers	Minor compression, traction, shear forces, prolonged limb positioning, repetitive local pressure, mild trauma	(paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)
Typical triggers	Quantified trigger data	In a 2025 literature review, triggers were traction/compression 57.8%, temperature change 3.4%, unclear 38.8%	(chen2025literaturereviewof pages 1-2)
Typical nerves affected	Most commonly involved nerves	Peroneal/common fibular and ulnar nerves are most frequent; median, radial, and brachial plexus involvement are also typical	(paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 4-5, chen2025literaturereviewof pages 1-2)
Typical manifestations	Common presentations	Foot drop/peroneal palsy, ulnar neuropathy at the elbow, carpal tunnel syndrome/median neuropathy, brachial plexopathy, focal numbness/paresthesia	(paassen2014pmp22relatedneuropathies pages 7-9, laudanski2024anestheticconsiderationsfor pages 4-5)
Phenotype frequencies	Selected recent review statistics	Typical weakness/numbness in vulnerable areas 63.7%; recurrent episodes 62%; atypical symptoms 29.8%; asymptomatic 6.5%; family history 64.5%; pes cavus 12.1%; pain/muscle atrophy 17.7%	(chen2025literaturereviewof pages 1-2)
Electrophysiology	Characteristic nerve conduction pattern	Demyelinating polyneuropathy pattern with increased distal motor latencies, especially median and peroneal; focal slowing/conduction block at entrapment sites; reduced sensory conduction velocities and SNAP amplitudes	(paassen2014pmp22relatedneuropathies pages 7-9, paassen2014pmp22relatedneuropathies pages 1-2, laudanski2024anestheticconsiderationsfor pages 4-5)
Electrophysiology	Suggestive electrodiagnostic signature	Bilateral median sensorimotor latency prolongation with at least unilateral peroneal motor abnormality is highly suggestive; sural responses may be reduced/absent in ~1/3	(laudanski2024anestheticconsiderationsfor pages 4-5)
Pathology	Nerve biopsy hallmark	Tomacula (sausage-like focal myelin thickening/overfolding), plus segmental de- and remyelination	(paassen2014pmp22relatedneuropathies pages 7-9, fabrizi2015disordersofperipheral pages 7-9)
Diagnostic modalities	First-line molecular confirmation	PMP22 copy-number testing for the recurrent deletion using MLPA, chromosomal microarray, FISH, or PCR-based methods	(laudanski2024anestheticconsiderationsfor pages 4-5, record2024wholegenomesequencing pages 3-5, cesaroni2025pmp22relatedneuropathiesa pages 13-15)
Diagnostic modalities	Sequencing methods	If deletion testing is negative or phenotype is atypical, consider PMP22 sequencing and/or neuropathy gene panels, WES, or WGS	(record2024wholegenomesequencing pages 3-5, record2024wholegenomesequencing pages 1-2, cesaroni2025pmp22relatedneuropathiesa pages 15-17)
Diagnostic modalities	Relative use of methods in recent review	Among 2,571 genetically tested PMP22-related neuropathy cases, MLPA 41.9%, NGS 20.4%, Sanger 17.8%, WES 0.4%, CGH/SNP array 1.4%	(cesaroni2025pmp22relatedneuropathiesa pages 13-15)
Diagnostic yield / cohorts	Large inherited neuropathy center data	In a 2024 Brain cohort of 1,515 inherited neuropathy patients, 72 HNPP cases (4.8%) were identified; PMP22 deletion represented 6.2% of solved genetic diagnoses	(record2024wholegenomesequencing pages 2-3, record2024wholegenomesequencing pages 1-2)
Imaging / adjunct tests	Supportive non-genetic tests	Nerve ultrasound and MRI/DTI can provide supportive structural information; muscle fatty infiltration has been proposed as a biomarker of progression	(laudanski2024anestheticconsiderationsfor pages 4-5, paassen2014pmp22relatedneuropathies pages 1-2)

Table: This table summarizes core identifiers, genetics, epidemiology, phenotype, electrophysiology, and diagnostic approaches for hereditary neuropathy with liability to pressure palsies. It is formatted for direct reuse as a knowledge-base scaffold with citation placeholders tied to available context IDs.

Primary visual evidence (mechanism)

Tomacula formation and compression-induced conduction block are shown in the Pmp22 super-enhancer deletion mouse model figures. (pantera2020pmp22superenhancerdeletion media 04ee1ad6, pantera2020pmp22superenhancerdeletion media 85bcd5c7)

References

(paassen2014pmp22relatedneuropathies pages 7-9): Barbara W van Paassen, Anneke J van der Kooi, Karin Y van Spaendonck-Zwarts, Camiel Verhamme, Frank Baas, and Marianne de Visser. Pmp22 related neuropathies: charcot-marie-tooth disease type 1a and hereditary neuropathy with liability to pressure palsies. Orphanet Journal of Rare Diseases, 9:38-38, Mar 2014. URL: https://doi.org/10.1186/1750-1172-9-38, doi:10.1186/1750-1172-9-38. This article has 258 citations and is from a peer-reviewed journal.
(laudanski2024anestheticconsiderationsfor pages 1-2): Krzysztof Laudanski, Omar Elmadhoun, Amal Mathew, Yul Kahn-Pascual, Mitchell J. Kerfeld, James Chen, Daniella C. Sisniega, and Francisco Gomez. Anesthetic considerations for patients with hereditary neuropathy with liability to pressure palsies: a narrative review. Healthcare, 12:858, Apr 2024. URL: https://doi.org/10.3390/healthcare12080858, doi:10.3390/healthcare12080858. This article has 1 citations.
(paassen2014pmp22relatedneuropathies pages 1-2): Barbara W van Paassen, Anneke J van der Kooi, Karin Y van Spaendonck-Zwarts, Camiel Verhamme, Frank Baas, and Marianne de Visser. Pmp22 related neuropathies: charcot-marie-tooth disease type 1a and hereditary neuropathy with liability to pressure palsies. Orphanet Journal of Rare Diseases, 9:38-38, Mar 2014. URL: https://doi.org/10.1186/1750-1172-9-38, doi:10.1186/1750-1172-9-38. This article has 258 citations and is from a peer-reviewed journal.
(OpenTargets Search: Hereditary neuropathy with liability to pressure palsies-PMP22): Open Targets Query (Hereditary neuropathy with liability to pressure palsies-PMP22, 2 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(savasta2025casereporthereditary pages 1-2): Salvatore Savasta, Fabiola Serra, Lucrezia Galimberti, Francesco Fabrizio Comisi, Marcello Cossu, Alessandro Vannelli, Maddalena Masala, Sara Tanca, and Stefania Murru. Case report: hereditary neuropathy with liability to pressure palsy (hnpp): the role of genetic investigation in diagnostic assessment. Frontiers in Genetics, Aug 2025. URL: https://doi.org/10.3389/fgene.2025.1613022, doi:10.3389/fgene.2025.1613022. This article has 2 citations and is from a peer-reviewed journal.
(chen2025literaturereviewof pages 1-2): Limin Chen, Hongbo Zhang, Chunnv Li, Nuo Yang, Jiangtao Wang, and Jianmin Liang. Literature review of clinical analysis of hereditary neuropathy with liability to pressure palsies. Journal of Neurology, Dec 2025. URL: https://doi.org/10.1007/s00415-024-12839-7, doi:10.1007/s00415-024-12839-7. This article has 7 citations and is from a domain leading peer-reviewed journal.
(fabrizi2015disordersofperipheral pages 7-9): Gian Maria Fabrizi and Giampietro Zanette. Disorders of peripheral nerves. ArXiv, pages 405-444, Jan 2015. URL: https://doi.org/10.1007/978-88-470-5755-5_35, doi:10.1007/978-88-470-5755-5_35. This article has 1 citations.
(li2013thepmp22gene pages 15-17): Jun Li, Brett Parker, Colin Martyn, Chandramohan Natarajan, and Jiasong Guo. The pmp22 gene and its related diseases. Molecular Neurobiology, 47:673-698, Dec 2013. URL: https://doi.org/10.1007/s12035-012-8370-x, doi:10.1007/s12035-012-8370-x. This article has 362 citations and is from a peer-reviewed journal.
(laudanski2024anestheticconsiderationsfor pages 4-5): Krzysztof Laudanski, Omar Elmadhoun, Amal Mathew, Yul Kahn-Pascual, Mitchell J. Kerfeld, James Chen, Daniella C. Sisniega, and Francisco Gomez. Anesthetic considerations for patients with hereditary neuropathy with liability to pressure palsies: a narrative review. Healthcare, 12:858, Apr 2024. URL: https://doi.org/10.3390/healthcare12080858, doi:10.3390/healthcare12080858. This article has 1 citations.
(pantera2020pmp22superenhancerdeletion pages 4-7): Harrison Pantera, Bo Hu, Daniel Moiseev, Chris Dunham, Jibraan Rashid, John J Moran, Kathleen Krentz, C Dustin Rubinstein, Seongsik Won, Jun Li, and John Svaren. Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves. Human molecular genetics, 29:1689-1699, Apr 2020. URL: https://doi.org/10.1093/hmg/ddaa082, doi:10.1093/hmg/ddaa082. This article has 9 citations and is from a domain leading peer-reviewed journal.
(pantera2020pmp22superenhancerdeletion pages 1-2): Harrison Pantera, Bo Hu, Daniel Moiseev, Chris Dunham, Jibraan Rashid, John J Moran, Kathleen Krentz, C Dustin Rubinstein, Seongsik Won, Jun Li, and John Svaren. Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves. Human molecular genetics, 29:1689-1699, Apr 2020. URL: https://doi.org/10.1093/hmg/ddaa082, doi:10.1093/hmg/ddaa082. This article has 9 citations and is from a domain leading peer-reviewed journal.
(pantera2020pmp22superenhancerdeletion media 04ee1ad6): Harrison Pantera, Bo Hu, Daniel Moiseev, Chris Dunham, Jibraan Rashid, John J Moran, Kathleen Krentz, C Dustin Rubinstein, Seongsik Won, Jun Li, and John Svaren. Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves. Human molecular genetics, 29:1689-1699, Apr 2020. URL: https://doi.org/10.1093/hmg/ddaa082, doi:10.1093/hmg/ddaa082. This article has 9 citations and is from a domain leading peer-reviewed journal.
(pantera2020pmp22superenhancerdeletion media 85bcd5c7): Harrison Pantera, Bo Hu, Daniel Moiseev, Chris Dunham, Jibraan Rashid, John J Moran, Kathleen Krentz, C Dustin Rubinstein, Seongsik Won, Jun Li, and John Svaren. Pmp22 super-enhancer deletion causes tomacula formation and conduction block in peripheral nerves. Human molecular genetics, 29:1689-1699, Apr 2020. URL: https://doi.org/10.1093/hmg/ddaa082, doi:10.1093/hmg/ddaa082. This article has 9 citations and is from a domain leading peer-reviewed journal.
(lehtilahti2022charcotmarietoothdiseasemolecular pages 25-28): M Lehtilahti. Charcot-marie-tooth disease: molecular epidemiology in northern ostrobothnia. Unknown journal, 2022.
(cesaroni2025pmp22relatedneuropathiesa pages 13-15): Carlo Alberto Cesaroni, Laura Caiazza, Giulia Pisanò, Martina Gnazzo, Giulia Sigona, Susanna Rizzi, Agnese Pantani, Daniele Frattini, and Carlo Fusco. Pmp22-related neuropathies: a systematic review. Genes, 16:1279, Oct 2025. URL: https://doi.org/10.3390/genes16111279, doi:10.3390/genes16111279. This article has 3 citations.
(cesaroni2025pmp22relatedneuropathiesa pages 15-17): Carlo Alberto Cesaroni, Laura Caiazza, Giulia Pisanò, Martina Gnazzo, Giulia Sigona, Susanna Rizzi, Agnese Pantani, Daniele Frattini, and Carlo Fusco. Pmp22-related neuropathies: a systematic review. Genes, 16:1279, Oct 2025. URL: https://doi.org/10.3390/genes16111279, doi:10.3390/genes16111279. This article has 3 citations.
(record2024wholegenomesequencing pages 1-2): Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, and Mary M Reilly. Whole genome sequencing increases the diagnostic rate in charcot-marie-tooth disease. Brain, 147:3144-3156, Mar 2024. URL: https://doi.org/10.1093/brain/awae064, doi:10.1093/brain/awae064. This article has 49 citations and is from a highest quality peer-reviewed journal.
(record2024wholegenomesequencing pages 3-5): Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, and Mary M Reilly. Whole genome sequencing increases the diagnostic rate in charcot-marie-tooth disease. Brain, 147:3144-3156, Mar 2024. URL: https://doi.org/10.1093/brain/awae064, doi:10.1093/brain/awae064. This article has 49 citations and is from a highest quality peer-reviewed journal.
(NCT02788734 chunk 1): Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies. University of South Florida. 2016. ClinicalTrials.gov Identifier: NCT02788734
(NCT05902351 chunk 1): Natural History Study for Charcot Marie Tooth Disease. Hereditary Neuropathy Foundation. 2013. ClinicalTrials.gov Identifier: NCT05902351
(cesaroni2025pmp22relatedneuropathiesa pages 12-13): Carlo Alberto Cesaroni, Laura Caiazza, Giulia Pisanò, Martina Gnazzo, Giulia Sigona, Susanna Rizzi, Agnese Pantani, Daniele Frattini, and Carlo Fusco. Pmp22-related neuropathies: a systematic review. Genes, 16:1279, Oct 2025. URL: https://doi.org/10.3390/genes16111279, doi:10.3390/genes16111279. This article has 3 citations.
(record2024wholegenomesequencing pages 2-3): Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, and Mary M Reilly. Whole genome sequencing increases the diagnostic rate in charcot-marie-tooth disease. Brain, 147:3144-3156, Mar 2024. URL: https://doi.org/10.1093/brain/awae064, doi:10.1093/brain/awae064. This article has 49 citations and is from a highest quality peer-reviewed journal.

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Inheritance

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Treatments

Source YAML

References & Deep Research

References

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Comprehensive Research Report: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)

Executive summary (current understanding)

1. Disease information

1.1 What is the disease?

1.2 Key identifiers (ontology/database cross-references)

1.3 Synonyms and alternative names

1.4 Evidence provenance (individual vs aggregated)

2. Etiology

2.1 Disease causal factors (primary causes)

2.2 Risk factors

2.3 Protective factors

2.4 Gene–environment interactions

3. Phenotypes

3.1 Core clinical phenotype (signs/symptoms)

3.2 Phenotype frequencies and clinical heterogeneity (recent compiled case series)

3.3 Suggested HPO terms (not exhaustive; based on reported clinical patterns)

4. Genetic / molecular information

4.1 Causal genes

4.2 Pathogenic variants (variant classes and frequencies)

4.3 Modifier genes / epigenetics

4.4 Disease-target association (curated evidence)

5. Environmental information

6. Mechanism / pathophysiology

6.1 Causal chain (from genotype to clinical episodes)

6.2 Primary mechanistic evidence (animal model; regulatory mechanism)

6.3 Suggested GO biological process terms (verify IDs during curation)

6.4 Suggested Cell Ontology (CL) terms (verify IDs during curation)

6.5 Suggested UBERON anatomical terms

7. Anatomical structures affected

7.1 Organ/system level

7.2 Tissue/cell level

7.3 Subcellular level

8. Temporal development (natural history)

8.1 Onset

8.2 Course/progression

9. Inheritance and population

9.1 Inheritance pattern

9.2 Epidemiology (statistics)

10. Diagnostics

10.1 Clinical/electrodiagnostic evaluation

10.2 Imaging

10.3 Genetic testing approach (real-world implementation)

10.4 Differential diagnosis

11. Outcome / prognosis

12. Treatment

12.1 Current standard management (real-world implementation)

12.2 Perioperative/anesthesia precautions (2024 expert synthesis)

12.3 Procedures and symptomatic interventions