👪

Inheritance

1

Autosomal recessive inheritance HP:0000007

Affected individuals harbor biallelic CAPN15 variants, consistent with autosomal recessive inheritance.

Autosomal recessive inheritance

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene."

Biallelic pathogenic CAPN15 variants in affected individuals support autosomal recessive inheritance.

⚙

Pathophysiology

4

Biallelic CAPN15 pathogenic variation

Biallelic CAPN15 pathogenic variants are the initiating genetic lesion. CAPN15 encodes a calpain-family protease, so the proximate molecular model is abnormal CAPN15-dependent protease biology during development.

CAPN15 link

proteolysis link ⚠ ABNORMAL

Downstream

Abnormal ocular morphogenesis CAPN15 variant effects manifest as abnormal ocular development.

Abnormal neurodevelopment CAPN15 variant effects manifest as abnormal nervous system development.

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene."

This supports biallelic CAPN15 variation as the primary disease mechanism.

Abnormal ocular morphogenesis

Reported biallelic missense variants are associated with ocular abnormalities.

eye development link ⚠ ABNORMAL

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

The exact abstract text links CAPN15 missense variants to eye abnormalities, supporting abnormal ocular morphogenesis as an atomic pathophysiology node.

Abnormal neurodevelopment

Reported biallelic missense variants are associated with developmental delay, and loss-of-function variants are associated with abnormal neurologic activity.

neuron link

nervous system development link ⚠ ABNORMAL

Downstream

Dandy-Walker malformation and cerebellar pathology CAPN15-related disease includes cerebellar pathology and Dandy-Walker malformation in the expanded phenotype.

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

The exact abstract text links CAPN15 variants to developmental delay and abnormal neurologic activity, supporting abnormal neurodevelopment as an atomic pathophysiology node.

Dandy-Walker malformation and cerebellar pathology

A subset of affected individuals show Dandy-Walker malformation, including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation, and mouse data support a role for CAPN15 in normal cerebellar development.

Purkinje cell link

cerebellum development link ⚠ ABNORMAL

cerebellum link

Show evidence (2 references)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy–Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation."

This directly supports Dandy-Walker malformation as part of the expanded human clinical phenotype.

DOI:10.1002/ajmg.a.63363 PARTIAL Model Organism

"To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development."

Mouse model data partially support a CAPN15 role in cerebellar development relevant to the human cerebellar phenotype.

⬡

Pathograph

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

●

Phenotypes

9

Cardiovascular 1

Cardiac malformations Abnormal heart morphology (HP:0001627)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists cardiac malformations among loss-of-function phenotypes.

Digestive 1

Anorectal involvement Anal atresia (HP:0002023)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 PARTIAL Human Clinical

"Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene."

This conservative GI phenotype uses the exact disease-name context from the abstract because OMIM #619318 could not be fetched by the repo reference tool. The cited syndrome name supports gastrointestinal involvement as part of the canonical disease context but does not provide detailed per-patient GI findings in the cached abstract.

Eye 1

Eye abnormalities Abnormal eye morphology (HP:0012372)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists eye abnormalities as part of the CAPN15-related phenotype.

Genitourinary 1

Genitourinary malformations Abnormality of the genitourinary system (HP:0000119)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists genitourinary malformations among loss-of-function phenotypes.

Head and Neck 1

Microcephaly Microcephaly (HP:0000252)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists microcephaly among loss-of-function phenotypes.

Nervous System 1

Global developmental delay Global developmental delay (HP:0001263)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists developmental delay as part of the phenotype.

Other 3

Craniofacial abnormalities Abnormality of the face (HP:0000271)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists craniofacial abnormalities among loss-of-function phenotypes.

Abnormal neurologic activity Abnormal nervous system physiology (HP:0012638)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal..."

This directly lists abnormal neurologic activity among loss-of-function phenotypes.

Dandy-Walker malformation Dandy-Walker malformation (HP:0001305)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy–Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15‐related disease."

This directly supports Dandy-Walker malformation as an expanded neurologic manifestation of CAPN15-related disease.

🧬

Genetic Associations

1

CAPN15 (Causal biallelic CAPN15 variants)

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder."

This directly identifies deleterious biallelic CAPN15 variants in molecularly confirmed affected individuals.

💊

Treatments

2

Supportive developmental and multisystem care

Action: supportive care MAXO:0000950

No disease-modifying therapy is established; care is supportive and directed to developmental, neurologic, ocular, cardiac, genitourinary, and other organ-specific findings.

Target Phenotypes: Global developmental delay ↗ Eye abnormalities ↗

Genetic counseling

Action: genetic counseling MAXO:0000079

Genetic counseling is appropriate for families because affected individuals harbor biallelic CAPN15 variants consistent with autosomal recessive inheritance.

Show evidence (1 reference)

DOI:10.1002/ajmg.a.63363 SUPPORT Human Clinical

"Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene."

Biallelic pathogenic variants support autosomal recessive recurrence-risk counseling.

{ }

Source YAML

click to show

name: Oculogastrointestinal-neurodevelopmental syndrome
creation_date: "2026-05-08T13:19:02Z"
updated_date: "2026-05-08T14:23:47Z"
description: >-
  Oculogastrointestinal-neurodevelopmental syndrome is an ultra-rare autosomal
  recessive CAPN15-related Mendelian disorder characterized by congenital
  ocular disease, developmental delay, and gastrointestinal involvement, with
  an expanded neurologic spectrum that includes Dandy-Walker malformation. The
  disorder corresponds to OMIM #619318.
category: Mendelian
parents:
- syndromic disease
- hereditary disease
synonyms:
- OGIN syndrome
- OGN
- Oculogastrointestinal neurodevelopmental syndrome
- CAPN15-related oculogastrointestinal neurodevelopmental syndrome
notes: >-
  OMIM #619318 identifies this CAPN15-related condition. Published summaries
  describe a genotype-phenotype distinction between biallelic missense variants
  and biallelic loss-of-function variants; this is retained as narrative
  genotype context rather than formal subtypes because the current abstract
  evidence does not define stable clinically named subtypes.
disease_term:
  preferred_term: oculogastrointestinal-neurodevelopmental syndrome
  term:
    id: MONDO:0036189
    label: oculogastrointestinal-neurodevelopmental syndrome
inheritance:
- name: Autosomal recessive inheritance
  description: >-
    Affected individuals harbor biallelic CAPN15 variants, consistent with
    autosomal recessive inheritance.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oculogastrointestinal neurodevelopmental syndrome has been described in
      seven previously published individuals who harbor biallelic pathogenic
      variants in the CAPN15 gene.
    explanation: >-
      Biallelic pathogenic CAPN15 variants in affected individuals support
      autosomal recessive inheritance.
genetic:
- name: CAPN15
  association: Causal biallelic CAPN15 variants
  gene_term:
    preferred_term: CAPN15
    term:
      id: hgnc:11182
      label: CAPN15
  notes: >-
    Both biallelic missense and biallelic loss-of-function variants are
    reported, with loss-of-function variants associated with a broader
    malformation and neurologic phenotype in the available clinical series.
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report six individuals from three unrelated families harboring
      biallelic deleterious variants in CAPN15 with phenotypes overlapping those
      previously described for this disorder.
    explanation: >-
      This directly identifies deleterious biallelic CAPN15 variants in
      molecularly confirmed affected individuals.
pathophysiology:
- name: Biallelic CAPN15 pathogenic variation
  description: >-
    Biallelic CAPN15 pathogenic variants are the initiating genetic lesion.
    CAPN15 encodes a calpain-family protease, so the proximate molecular model
    is abnormal CAPN15-dependent protease biology during development.
  genes:
  - preferred_term: CAPN15
    term:
      id: hgnc:11182
      label: CAPN15
  biological_processes:
  - preferred_term: proteolysis
    modifier: ABNORMAL
    term:
      id: GO:0006508
      label: proteolysis
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oculogastrointestinal neurodevelopmental syndrome has been described in
      seven previously published individuals who harbor biallelic pathogenic
      variants in the CAPN15 gene.
    explanation: >-
      This supports biallelic CAPN15 variation as the primary disease mechanism.
  downstream:
  - target: Abnormal ocular morphogenesis
    description: >-
      CAPN15 variant effects manifest as abnormal ocular development.
  - target: Abnormal neurodevelopment
    description: >-
      CAPN15 variant effects manifest as abnormal nervous system development.
- name: Abnormal ocular morphogenesis
  description: >-
    Reported biallelic missense variants are associated with ocular
    abnormalities.
  biological_processes:
  - preferred_term: eye development
    modifier: ABNORMAL
    term:
      id: GO:0001654
      label: eye development
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: >-
      The exact abstract text links CAPN15 missense variants to eye
      abnormalities, supporting abnormal ocular morphogenesis as an atomic
      pathophysiology node.
- name: Abnormal neurodevelopment
  description: >-
    Reported biallelic missense variants are associated with developmental
    delay, and loss-of-function variants are associated with abnormal
    neurologic activity.
  biological_processes:
  - preferred_term: nervous system development
    modifier: ABNORMAL
    term:
      id: GO:0007399
      label: nervous system development
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: >-
      The exact abstract text links CAPN15 variants to developmental delay and
      abnormal neurologic activity, supporting abnormal neurodevelopment as an
      atomic pathophysiology node.
  downstream:
  - target: Dandy-Walker malformation and cerebellar pathology
    description: >-
      CAPN15-related disease includes cerebellar pathology and Dandy-Walker
      malformation in the expanded phenotype.
- name: Dandy-Walker malformation and cerebellar pathology
  description: >-
    A subset of affected individuals show Dandy-Walker malformation, including
    hypoplastic vermis, fourth ventricle enlargement, and torcular elevation,
    and mouse data support a role for CAPN15 in normal cerebellar development.
  locations:
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  cell_types:
  - preferred_term: Purkinje cell
    term:
      id: CL:0000121
      label: Purkinje cell
  biological_processes:
  - preferred_term: cerebellum development
    modifier: ABNORMAL
    term:
      id: GO:0021549
      label: cerebellum development
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the individuals affected, four demonstrate radiographic evidence of
      the classical triad of Dandy–Walker malformation including hypoplastic
      vermis, fourth ventricle enlargement, and torcular elevation.
    explanation: >-
      This directly supports Dandy-Walker malformation as part of the expanded
      human clinical phenotype.
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: PARTIAL
    evidence_source: MODEL_ORGANISM
    snippet: >-
      To corroborate these novel clinical findings, we present supporting data
      from the mouse model suggesting an important role for this protein in
      normal cerebellar development.
    explanation: >-
      Mouse model data partially support a CAPN15 role in cerebellar
      development relevant to the human cerebellar phenotype.
phenotypes:
- name: Eye abnormalities
  category: Ophthalmologic
  description: Eye abnormalities are a core manifestation of CAPN15-related disease.
  phenotype_term:
    preferred_term: eye abnormalities
    term:
      id: HP:0012372
      label: Abnormal eye morphology
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: >-
      This directly lists eye abnormalities as part of the CAPN15-related
      phenotype.
- name: Global developmental delay
  category: Neurodevelopmental
  description: Developmental delay is a core neurodevelopmental manifestation.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists developmental delay as part of the phenotype.
- name: Microcephaly
  category: Neurologic
  description: Microcephaly is reported among loss-of-function CAPN15 phenotypes.
  phenotype_term:
    preferred_term: Microcephaly
    term:
      id: HP:0000252
      label: Microcephaly
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists microcephaly among loss-of-function phenotypes.
- name: Craniofacial abnormalities
  category: Craniofacial
  description: Craniofacial abnormalities are reported among loss-of-function CAPN15 phenotypes.
  phenotype_term:
    preferred_term: Craniofacial abnormalities
    term:
      id: HP:0000271
      label: Abnormality of the face
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists craniofacial abnormalities among loss-of-function phenotypes.
- name: Cardiac malformations
  category: Cardiovascular
  description: Cardiac malformations are reported among loss-of-function CAPN15 phenotypes.
  phenotype_term:
    preferred_term: Cardiac malformations
    term:
      id: HP:0001627
      label: Abnormal heart morphology
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists cardiac malformations among loss-of-function phenotypes.
- name: Genitourinary malformations
  category: Genitourinary
  description: Genitourinary malformations are reported among loss-of-function CAPN15 phenotypes.
  phenotype_term:
    preferred_term: Genitourinary malformations
    term:
      id: HP:0000119
      label: Abnormality of the genitourinary system
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists genitourinary malformations among loss-of-function phenotypes.
- name: Abnormal neurologic activity
  category: Neurologic
  description: Abnormal neurologic activity is reported among loss-of-function CAPN15 phenotypes.
  phenotype_term:
    preferred_term: Abnormal neurologic activity
    term:
      id: HP:0012638
      label: Abnormal nervous system physiology
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Biallelic missense variants have been reported to demonstrate a phenotype
      of eye abnormalities and developmental delay, while biallelic loss of
      function variants exhibit phenotypes including microcephaly and
      craniofacial abnormalities, cardiac and genitourinary malformations, and
      abnormal neurologic activity.
    explanation: This directly lists abnormal neurologic activity among loss-of-function phenotypes.
- name: Anorectal involvement
  category: Gastrointestinal
  description: >-
    Gastrointestinal involvement is part of the named
    oculogastrointestinal-neurodevelopmental syndrome context.
  phenotype_term:
    preferred_term: Anorectal involvement
    term:
      id: HP:0002023
      label: Anal atresia
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oculogastrointestinal neurodevelopmental syndrome has been described in
      seven previously published individuals who harbor biallelic pathogenic
      variants in the CAPN15 gene.
    explanation: >-
      This conservative GI phenotype uses the exact disease-name context from
      the abstract because OMIM #619318 could not be fetched by the repo
      reference tool. The cited syndrome name supports gastrointestinal
      involvement as part of the canonical disease context but does not provide
      detailed per-patient GI findings in the cached abstract.
- name: Dandy-Walker malformation
  category: Neurologic
  description: >-
    Dandy-Walker malformation expands the neurologic phenotype of
    CAPN15-related disease.
  phenotype_term:
    preferred_term: Dandy-Walker malformation
    term:
      id: HP:0001305
      label: Dandy-Walker malformation
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our findings add six molecularly confirmed cases to the literature and
      additionally establish a new association of Dandy–Walker malformation with
      biallelic CAPN15 variants, thereby expanding the neurologic spectrum among
      patients affected by CAPN15‐related disease.
    explanation: >-
      This directly supports Dandy-Walker malformation as an expanded
      neurologic manifestation of CAPN15-related disease.
diagnosis:
- name: Whole exome sequencing for syndromic congenital ocular dysgenesis
  description: >-
    Whole exome sequencing can identify rare syndromic ocular dysgenesis
    diagnoses, including oculogastrointestinal-neurodevelopmental syndrome, when
    congenital ocular phenotypes overlap with other anterior segment dysgenesis
    disorders.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: DOI:10.1038/s10038-024-01237-6
    reference_title: >-
      A bird's eye view on the use of whole exome sequencing in rare congenital
      ophthalmic diseases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most importantly, the use of WES has allowed us to both assess variants
      in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to
      identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental
      syndrome and Jacobsen syndrome).
    explanation: >-
      This supports whole exome sequencing as diagnostically useful for rare
      ocular dysgenesis phenotypes including this syndrome.
treatments:
- name: Supportive developmental and multisystem care
  description: >-
    No disease-modifying therapy is established; care is supportive and directed
    to developmental, neurologic, ocular, cardiac, genitourinary, and other
    organ-specific findings.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  target_phenotypes:
  - preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  - preferred_term: Eye abnormalities
    term:
      id: HP:0012372
      label: Abnormal eye morphology
- name: Genetic counseling
  description: >-
    Genetic counseling is appropriate for families because affected individuals
    harbor biallelic CAPN15 variants consistent with autosomal recessive
    inheritance.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: DOI:10.1002/ajmg.a.63363
    reference_title: >-
      Novel association of Dandy-Walker malformation with CAPN15 variants
      expands the phenotype of oculogastrointestinal neurodevelopmental
      syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Oculogastrointestinal neurodevelopmental syndrome has been described in
      seven previously published individuals who harbor biallelic pathogenic
      variants in the CAPN15 gene.
    explanation: >-
      Biallelic pathogenic variants support autosomal recessive recurrence-risk
      counseling.
references:
- reference: DOI:10.1002/ajmg.a.63363
  title: >-
    Novel association of Dandy-Walker malformation with CAPN15 variants expands
    the phenotype of oculogastrointestinal neurodevelopmental syndrome
  found_in:
  - Oculogastrointestinal-Neurodevelopmental_Syndrome-deep-research-falcon.md
  findings:
  - statement: >-
      CAPN15 variants expand the phenotype of oculogastrointestinal
      neurodevelopmental syndrome to include Dandy-Walker malformation.
    supporting_text: >-
      Our findings add six molecularly confirmed cases to the literature and
      additionally establish a new association of Dandy–Walker malformation with
      biallelic CAPN15 variants, thereby expanding the neurologic spectrum among
      patients affected by CAPN15‐related disease.
- reference: DOI:10.1038/s10038-024-01237-6
  title: >-
    A bird's eye view on the use of whole exome sequencing in rare congenital
    ophthalmic diseases
  found_in:
  - Oculogastrointestinal-Neurodevelopmental_Syndrome-deep-research-falcon.md
  findings:
  - statement: >-
      Whole exome sequencing helps identify oculogastrointestinal-
      neurodevelopmental syndrome among rare syndromic ocular dysgenesis
      phenotypes.
    supporting_text: >-
      Most importantly, the use of WES has allowed us to both assess variants
      in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to
      identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental
      syndrome and Jacobsen syndrome).
datasets:

📚

References & Deep Research

References

2

DOI:10.1002/ajmg.a.63363

Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome

1 finding

CAPN15 variants expand the phenotype of oculogastrointestinal neurodevelopmental syndrome to include Dandy-Walker malformation.

"Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy–Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15‐related disease."

DOI:10.1038/s10038-024-01237-6

A bird's eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases

1 finding

Whole exome sequencing helps identify oculogastrointestinal- neurodevelopmental syndrome among rare syndromic ocular dysgenesis phenotypes.

"Most importantly, the use of WES has allowed us to both assess variants in known ASD genes (i.e., CYP1B1, ITPR1, MAB21L1, PXDN, and PITX2) and to identify rarer phenotypes (i.e., MIDAS, oculogastrointestinal-neurodevelopmental syndrome and Jacobsen syndrome)."

Deep Research

1

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 12 citations 2026-05-08T09:28:55.328650

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: Oculogastrointestinal-neurodevelopmental syndrome
MONDO ID: (if available)
Category: Mendelian

Research Objectives

Please provide a comprehensive research report on Oculogastrointestinal-neurodevelopmental syndrome 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: Oculogastrointestinal-neurodevelopmental syndrome (CAPN15-related)

Target disease

Disease name: Oculogastrointestinal-neurodevelopmental syndrome (OGN)
Category: Mendelian (autosomal recessive)
Causal gene: CAPN15

Disease name	Synonyms	OMIM	Causal gene	Inheritance	Key publications	Reported case counts	Key novel finding
Oculogastrointestinal-neurodevelopmental syndrome	Oculogastrointestinal neurodevelopmental syndrome; CAPN15-related oculogastrointestinal-neurodevelopmental syndrome	619318	CAPN15	Autosomal recessive (biallelic pathogenic variants)	Beaman et al. Am J Med Genet A (Aug 2023). DOI: https://doi.org/10.1002/ajmg.a.63363; Zucco et al. J Hum Genet (Mar 2024). DOI: https://doi.org/10.1038/s10038-024-01237-6	7 previously published individuals + 6 new molecularly confirmed individuals reported by Beaman et al. = 13 total reported individuals at that time; Zucco 2024 summarizes the disorder as described in <10 published individuals prior to newer case additions (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)	Dandy–Walker malformation added to the phenotype spectrum in Beaman et al. 2023, including the classical triad in 4 affected individuals (hypoplastic vermis, fourth ventricle enlargement, torcular elevation) (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 3-5)
Publication detail	—	—	—	—	Beaman et al.: publication date Aug 2023, URL https://doi.org/10.1002/ajmg.a.63363 (beaman2023novelassociationof pages 1-3); Zucco et al.: publication date Mar 2024, URL https://doi.org/10.1038/s10038-024-01237-6 (zucco2024abird’seye pages 9-10)	—	—

Table: This table summarizes the core identifiers, inheritance, causal gene, key literature, case counts, and the major 2023 phenotype expansion for oculogastrointestinal-neurodevelopmental syndrome. It is useful as a compact reference for disease knowledge base curation.

1. Disease information

Overview / definition

Oculogastrointestinal-neurodevelopmental syndrome is an ultra-rare, autosomal-recessive, multisystem congenital disorder caused by biallelic pathogenic variants in CAPN15, characterized by congenital ocular malformations, gastrointestinal/anorectal anomalies, and neurodevelopmental impairment, with expanding evidence for hindbrain malformations including Dandy–Walker malformation. (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

Key identifiers

OMIM: #619318 (listed for oculogastrointestinal neurodevelopmental syndrome in a 2023 primary case series) (beaman2023novelassociationof pages 1-3)
Other identifiers (Orphanet, MONDO, MeSH, ICD-10/ICD-11): Not located in the retrieved sources; additional targeted database lookups would be required.

Synonyms / alternative names

Oculogastrointestinal neurodevelopmental syndrome (OGN) (beaman2023novelassociationof pages 1-3)
Oculogastrointestinal-neurodevelopmental syndrome (hyphenated form used in 2024 review) (zucco2024abird’seye pages 9-10)
CAPN15-related oculogastrointestinal-neurodevelopmental syndrome (gene-based synonym used in the literature context) (zucco2024abird’seye pages 9-10)

Evidence base type

The available evidence is derived primarily from individual/family case reports and case series with molecular confirmation, with supportive animal model and in vitro patient-fibroblast functional studies in at least one 2023 report. (beaman2023novelassociationof pages 5-6, beaman2023novelassociationof pages 6-8)

2. Etiology

Disease causal factors

Primary cause: Biallelic pathogenic variants in CAPN15 (autosomal recessive). (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

Abstract quote (primary literature, 2023): The 2023 case series states the syndrome “has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene” and reports additional molecularly confirmed individuals. (beaman2023novelassociationof pages 1-3)

Risk factors

Genetic risk factor: Having biallelic deleterious CAPN15 variants; several reported families include consanguinity, consistent with enrichment of homozygous rare alleles in such pedigrees. (beaman2023novelassociationof pages 5-6)
Environmental risk factors: No evidence found in retrieved sources; for a Mendelian congenital syndrome, environmental risk factors are not currently established.

Protective factors / gene–environment interactions

No protective factors or gene–environment interactions were identified in the retrieved sources.

3. Phenotypes

Core phenotype domains (human)

The reported phenotype spans ocular, gastrointestinal/anorectal, neurologic/neurodevelopmental, growth, and multi-organ congenital anomalies.

Ocular phenotypes (congenital)

Examples reported include microphthalmia, coloboma, corneal clouding, iridocorneal adhesions, and strabismus-related findings. (beaman2023novelassociationof pages 6-8, zucco2024abird’seye pages 9-10)

Suggested HPO terms (non-exhaustive, based on reported features): - Microphthalmia (HP:0000568) - Coloboma (HP:0000589) - Corneal opacity / clouding (HP:0007957) - Anterior segment dysgenesis / iridocorneal adhesions (HP:0007830 or related ASD terms) - Strabismus (HP:0000486)

Gastrointestinal/anorectal phenotypes

Reported congenital GI/anorectal anomalies include anal atresia and rectovestibular fistula. (beaman2023novelassociationof pages 6-8, beaman2023novelassociationof pages 3-5)

Suggested HPO terms: - Anal atresia (HP:0002023) - Rectovaginal/rectovestibular fistula (HPO term selection depends on exact anatomy; rectovaginal fistula HP:0000141 may be used as a nearest term if rectovestibular-specific is unavailable)

Neurodevelopmental / neurologic phenotypes

Neurodevelopmental involvement is common. In a 2023 series, 10/10 individuals who underwent neurodevelopmental evaluation were reported to have neurodevelopmental issues. (beaman2023novelassociationof pages 6-8)

Additional neurologic features include seizures/abnormal neurologic activity in more severe cases. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 6-8)

Suggested HPO terms: - Global developmental delay (HP:0001263) - Intellectual disability (HP:0001249) - Seizures (HP:0001250) - Autism spectrum disorder (HP:0000729) (reported as part of milder missense-associated presentations) (beaman2023novelassociationof pages 8-10)

Brain malformations (key recent expansion)

A major 2023 expansion is the association with Dandy–Walker malformation, with radiographic evidence of the classic triad (hypoplastic vermis, enlarged fourth ventricle, torcular elevation) in 4 affected individuals (and in the series, 4/5 imaged individuals showed the classical triad). (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 5-6)

Suggested HPO terms: - Dandy–Walker malformation (HP:0001305) (explicitly referenced) (beaman2023novelassociationof pages 3-5) - Hydrocephalus / ventriculomegaly (HP:0000238 / HP:0002119) (beaman2023novelassociationof pages 6-8)

Multi-organ congenital anomalies

More severe presentations (often associated with loss-of-function CAPN15 variants) include microcephaly, craniofacial anomalies, cardiac malformations, and genitourinary malformations. (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

Suggested HPO terms: - Microcephaly (HP:0000252) - Congenital heart defect (HP:0001627) - Abnormality of the genitourinary system (HP:0000119)

Age of onset / progression

The phenotype is predominantly congenital (ocular and structural anomalies) with early-life manifestations of neurodevelopmental delay and possible progressive complications such as hydrocephalus requiring monitoring. (beaman2023novelassociationof pages 6-8, beaman2023novelassociationof pages 5-6)

Quality-of-life impact

Direct quality-of-life instruments (e.g., PedsQL, PROMIS) were not reported in the retrieved sources; however, the combination of congenital ocular impairment, neurodevelopmental disability, seizures, and major congenital malformations implies substantial lifelong functional impact. (beaman2023novelassociationof pages 6-8, zucco2024abird’seye pages 9-10)

4. Genetic / molecular information

Causal gene

CAPN15 (also referenced as CAPN15/SOLH in the 2023 report). (beaman2023novelassociationof pages 3-5, beaman2023novelassociationof pages 13-18)

Inheritance

Autosomal recessive with biallelic pathogenic variants, including homozygous and compound heterozygous states; heterozygous carriers may be unaffected. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 13-18)

Pathogenic variant types and genotype–phenotype correlation

A consistent theme is variant-class correlation: - Biallelic missense variants: tend to be associated with milder phenotypes, prominently ocular anomalies and developmental delay. (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10, beaman2023novelassociationof pages 8-10) - Biallelic loss-of-function variants (frameshift, exon-skipping leading to frameshift, whole-gene deletion): associated with more severe syndromic disease, including microcephaly, craniofacial/cardiac/genitourinary anomalies, and abnormal neurologic activity, and in 2023 were associated with Dandy–Walker malformation/cerebellar pathology. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 5-6, beaman2023novelassociationof pages 8-10)

Examples of variant classes mentioned in the 2023 report include frameshift variants (e.g., c.2164delC; c.754dupC) and a missense variant p.Leu865Pro sometimes in trans with a whole-gene deletion. (beaman2023novelassociationof pages 5-6, beaman2023novelassociationof pages 3-5, beaman2023novelassociationof pages 8-10)

Allele frequency / population databases

At least one deleterious missense variant (p.Leu865Pro) is reported as absent from gnomAD, supporting rarity. (beaman2023novelassociationof pages 6-8)

Functional consequences

Evidence from patient-derived cells and protein modeling supports loss of transcript/protein for truncating alleles and protein destabilization for at least one missense allele: - Patient fibroblast assays (RT-PCR/Western blot) showed reduced mRNA and/or loss of full-length protein depending on allele class. (beaman2023novelassociationof pages 5-6, beaman2023novelassociationof pages 13-18) - Structural modeling (AlphaFold-based) and in silico predictions supported deleterious impact of p.Leu865Pro. (beaman2023novelassociationof pages 6-8, beaman2023novelassociationof pages 13-18)

Protein features and current understanding

CAPN15 is described as a non-classical calpain protease with N-terminal RanBP2-type zinc fingers, a calpain protease domain, and a distinctive C-terminal SOLH-like domain; the overall biological function remains poorly understood, but is implicated in development. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 3-5)

Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes or epigenetic signatures were identified in retrieved sources. Some cases include copy-number variation (whole-gene deletion) as part of the biallelic pathogenic state, detected via CNV analysis. (beaman2023novelassociationof pages 8-10)

5. Environmental information

No non-genetic environmental contributors, lifestyle risks, or infectious triggers were identified in retrieved sources; the condition is currently understood as a primarily genetic congenital disorder. (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

6. Mechanism / pathophysiology

Proposed causal chain (current evidence-based model)

Biallelic CAPN15 pathogenic variation → reduced CAPN15 mRNA/protein abundance or destabilized protein (functional assays/in silico modeling). (beaman2023novelassociationof pages 5-6, beaman2023novelassociationof pages 6-8)
Impaired CAPN15 function during development → abnormalities in ocular development and brain development, supported by cross-species evidence.
Drosophila CAPN15 homolog (Sol) is required for optic tract neuron maintenance, suggesting a role in neural development/maintenance. (beaman2023novelassociationof pages 3-5)
Mouse data demonstrate CAPN15/SOLH expression in the cerebellum, including in Purkinje cells, supporting a role in cerebellar maturation and plausibly relating to Dandy–Walker spectrum malformations. (beaman2023novelassociationof pages 8-10, beaman2023novelassociationof pages 18-20)
Developmental disruption manifests as the clinical triad: ocular anomalies + GI/anorectal malformations + neurodevelopmental disorder, with severity depending on the degree of CAPN15 functional loss (missense vs LoF). (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

Pathways and processes (evidence level: hypothesis-supporting)

The 2023 case series notes predicted binding partners implicating ubiquitin/proteasome and cell-division roles; however, direct pathway proof in human tissue is not established in the retrieved evidence. (beaman2023novelassociationof pages 8-10)

Suggested GO biological process terms (hypothesis-driven, to be validated): - Nervous system development - Cerebellum development - Eye development - Proteolysis

Suggested CL cell types: - Purkinje cell (CL:0000121) (supported by expression in calbindin+ Purkinje-associated layers) (beaman2023novelassociationof pages 8-10)

7. Anatomical structures affected

Based on reported clinical and imaging features, affected systems include: - Eye (UBERON:0000970) (beaman2023novelassociationof pages 6-8, zucco2024abird’seye pages 9-10) - Cerebellum / hindbrain (UBERON:0002037 / UBERON:0005291) including vermis and posterior fossa structures in Dandy–Walker malformation (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 6-8) - Anorectal region / hindgut (UBERON:0001052 or relevant hindgut/anus terms) (beaman2023novelassociationof pages 6-8) - Possible heart and kidney/genitourinary system involvement in severe presentations (beaman2023novelassociationof pages 1-3, zucco2024abird’seye pages 9-10)

Subcellular localization/compartments were not established in retrieved sources.

8. Temporal development

Onset: Predominantly congenital structural anomalies (ocular and GI/anorectal), with infant/childhood emergence/recognition of neurodevelopmental delay and seizures in some. (beaman2023novelassociationof pages 6-8, beaman2023novelassociationof pages 1-3)
Course: Appears chronic/lifelong, with neurodevelopmental disability a persistent feature; complications such as ventriculomegaly/hydrocephalus may evolve and require follow-up. (beaman2023novelassociationof pages 6-8)

9. Inheritance and population

Rarity and reported cases (statistics)

A 2024 review describes the syndrome as “ultra-rare” and “described in less than ten published individuals” (context: summarizing the disorder). (zucco2024abird’seye pages 9-10)
A 2023 case series states that 7 individuals had been previously published and reports 6 additional molecularly confirmed individuals (bringing the total to approximately 13 reported by that time, assuming no overlap). (beaman2023novelassociationof pages 1-3)

Prevalence/incidence

No prevalence or incidence estimates were found in the retrieved sources.

Inheritance

Autosomal recessive with biallelic variants; consanguinity was present in some pedigrees. (beaman2023novelassociationof pages 5-6)

10. Diagnostics

Clinical recognition

Suspicion should arise from the combination of: - Congenital ocular malformations (e.g., microphthalmia/coloboma) - Anorectal/GI malformations - Neurodevelopmental impairment and/or seizures - Brain malformation such as Dandy–Walker spectrum features on imaging (beaman2023novelassociationof pages 6-8, beaman2023novelassociationof pages 1-3)

Genetic testing and real-world implementation

Whole exome sequencing (WES) and rapid whole genome sequencing (WGS) were used to establish molecular diagnoses in the 2023 series, and WES is highlighted as enabling diagnosis of OGN among rare congenital ophthalmic disorders. (beaman2023novelassociationof pages 3-5, zucco2024abird’seye pages 9-10)
Chromosomal microarray may be non-diagnostic in some cases. (beaman2023novelassociationof pages 5-6)
Analysis/interpretation approaches reported include phenotype-driven prioritization (Phevor), population filtering (gnomAD), in silico pathogenicity scores (e.g., CADD/REVEL), ACMG/AMP classification, and Sanger confirmation/segregation. (beaman2023novelassociationof pages 3-5)

Imaging

Neuroimaging may show Dandy–Walker features including hypoplastic vermis, fourth ventricle enlargement, torcular elevation, posterior fossa cysts, and hydrocephalus/ventriculomegaly. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 6-8)

Differential diagnosis

No structured differential diagnosis list was available in retrieved sources; based on phenotype, overlaps likely include other syndromic microphthalmia/coloboma disorders and syndromic anorectal malformation conditions.

11. Outcome / prognosis

No formal survival, mortality, or life expectancy statistics were available in retrieved sources. Available evidence suggests morbidity is driven by the severity of congenital malformations, degree of visual impairment, neurodevelopmental disability, epilepsy, and possible hydrocephalus. (beaman2023novelassociationof pages 6-8, zucco2024abird’seye pages 9-10)

12. Treatment

Current management (evidence limitations)

No disease-specific targeted therapies were identified in the retrieved sources. Management is therefore best described as supportive and multidisciplinary, tailored to organ involvement: - Ophthalmologic management for ocular anomalies - Surgical management of anorectal malformations - Neurodevelopmental therapies (PT/OT/speech) and educational support - Antiseizure treatment if epilepsy is present - Monitoring/management of hydrocephalus and associated neurosurgical needs (beaman2023novelassociationof pages 6-8, zucco2024abird’seye pages 9-10)

Clinical trials

A ClinicalTrials.gov-style search for “CAPN15” or “oculogastrointestinal(-neurodevelopmental)” retrieved no clearly relevant interventional trials in the current tool output. (clinical trial search tool result; no citable NCTs returned)

Suggested MAXO terms (management-oriented): - Surgical repair of anorectal malformation - Vision care / ophthalmologic management - Seizure management - Developmental therapy

13. Prevention

Because OGN is a rare autosomal-recessive disorder, prevention is primarily genetic: - Carrier testing and genetic counseling in affected families - Prenatal or preimplantation genetic testing when familial pathogenic variants are known No environmental primary prevention measures were identified.

14. Other species / natural disease

No naturally occurring veterinary analogs were identified in retrieved sources. However, Drosophila and mouse provide functional evidence relevant to developmental roles of CAPN15. (beaman2023novelassociationof pages 3-5, beaman2023novelassociationof pages 8-10)

15. Model organisms

Drosophila: CAPN15 homolog (Sol) required for optic tract neuron maintenance; mutants show neurodegeneration/reduced brain volume, supporting neuro-ocular relevance. (beaman2023novelassociationof pages 3-5)
Mouse: Capn15 knockout and expression studies support roles in brain development/plasticity; cerebellar expression is seen in postnatal development with enrichment in Purkinje-associated layers and persistence into adulthood, supporting plausibility for cerebellar malformation phenotypes in humans. (beaman2023novelassociationof pages 8-10, beaman2023novelassociationof pages 18-20)

2023–2024 highlights (latest research and applications)

Phenotype expansion and case accrual (2023): Beaman et al. (Aug 2023; https://doi.org/10.1002/ajmg.a.63363) added six molecularly confirmed individuals and established an association with Dandy–Walker malformation, with classical triad in 4 affected individuals, supported by mouse cerebellar expression data. (beaman2023novelassociationof pages 1-3, beaman2023novelassociationof pages 5-6)
Diagnostic implementation (2024): Zucco et al. (Mar 2024; https://doi.org/10.1038/s10038-024-01237-6) emphasizes WES as pivotal for diagnosing rare congenital ocular dysgenesis conditions, explicitly including OGN, and summarizes that severity differs for loss-of-function vs missense CAPN15 variants. (zucco2024abird’seye pages 9-10)

Key evidence gaps / limitations of this report

Identifiers beyond OMIM (Orphanet, MONDO, MeSH, ICD) were not captured from the retrieved sources.
PMIDs were not available in the tool-provided excerpts/metadata; this report therefore cites the retrieved full-text evidence context IDs and provides DOIs/URLs and publication months/years.
Detailed variant-by-variant frequencies, formal natural history, quality-of-life metrics, and treatment outcomes were not available in the retrieved evidence.

Key references (with publication dates and URLs)

Beaman MM et al. American Journal of Medical Genetics Part A Aug 2023. “Novel association of Dandy–Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.” https://doi.org/10.1002/ajmg.a.63363 (beaman2023novelassociationof pages 1-3)
Zucco J et al. Journal of Human Genetics Mar 2024. “A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases.” https://doi.org/10.1038/s10038-024-01237-6 (zucco2024abird’seye pages 9-10)

References

(beaman2023novelassociationof pages 1-3): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(zucco2024abird’seye pages 9-10): Jessica Zucco, Federica Baldan, Lorenzo Allegri, Elisa Bregant, Nadia Passon, Alessandra Franzoni, Angela Valentina D’Elia, Flavio Faletra, Giuseppe Damante, and Catia Mio. A bird’s eye view on the use of whole exome sequencing in rare congenital ophthalmic diseases. Journal of Human Genetics, 69:271-282, Mar 2024. URL: https://doi.org/10.1038/s10038-024-01237-6, doi:10.1038/s10038-024-01237-6. This article has 9 citations and is from a peer-reviewed journal.
(beaman2023novelassociationof pages 3-5): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(beaman2023novelassociationof pages 5-6): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(beaman2023novelassociationof pages 6-8): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(beaman2023novelassociationof pages 8-10): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(beaman2023novelassociationof pages 13-18): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.
(beaman2023novelassociationof pages 18-20): M. Makenzie Beaman, Lucia Guidugli, Monia Hammer, Chelsea Barrows, Anne Gregor, Sangmoon Lee, Kristen L. Deak, Marie T. McDonald, Courtney Jensen, Maha S. Zaki, Amira T. Masri, Charlotte A. Hobbs, Joseph G. Gleeson, and Jennifer L. Cohen. Novel association of dandy–walker malformation with capn15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome. American Journal of Medical Genetics Part A, 191:2757-2767, Aug 2023. URL: https://doi.org/10.1002/ajmg.a.63363, doi:10.1002/ajmg.a.63363. This article has 18 citations.

Ask OpenScientist

OpenScientist Report

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: Oculogastrointestinal-neurodevelopmental syndrome (CAPN15-related)

Target disease

1. Disease information

Overview / definition

Key identifiers

Synonyms / alternative names

Evidence base type

2. Etiology

Disease causal factors

Risk factors

Protective factors / gene–environment interactions

3. Phenotypes

Core phenotype domains (human)

Ocular phenotypes (congenital)

Gastrointestinal/anorectal phenotypes

Neurodevelopmental / neurologic phenotypes

Brain malformations (key recent expansion)

Multi-organ congenital anomalies

Age of onset / progression

Quality-of-life impact

4. Genetic / molecular information

Causal gene

Inheritance

Pathogenic variant types and genotype–phenotype correlation

Allele frequency / population databases

Functional consequences

Protein features and current understanding

Modifier genes / epigenetics / chromosomal abnormalities

5. Environmental information

6. Mechanism / pathophysiology

Proposed causal chain (current evidence-based model)

Pathways and processes (evidence level: hypothesis-supporting)

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

Rarity and reported cases (statistics)

Prevalence/incidence

Inheritance

10. Diagnostics

Clinical recognition

Genetic testing and real-world implementation

Imaging

Differential diagnosis

11. Outcome / prognosis

12. Treatment

Current management (evidence limitations)

Clinical trials

13. Prevention