MED17-Related Disorder

Mendelian MONDO:0013351 Pathograph 9 Show in embeddings browser Autosomal recessive intellectual disability Neurodevelopmental disorder Mediator complex-associated disorder

MED17-related disorder (MCPHA) is a rare autosomal recessive neurodevelopmental and neurodegenerative disorder caused by biallelic variants in MED17, a subunit of the head module of the Mediator transcriptional coactivator complex, with a recurrent homozygous founder allele (p.Leu371Pro) in Caucasus-Jewish families. Infants are normal at birth and then develop postnatal progressive microcephaly, spasticity, epilepsy, and profound psychomotor retardation; brain MRI shows marked cerebral and cerebellar atrophy with a severe myelination defect. Prognosis is grave. Because MED17 acts in the constitutive head module rather than the dissociable kinase module, MCPHA is one of the founding recessive "core-module" MEDopathies; the p.L371P allele inactivated the homologous yeast gene SRB4 in complementation assays, supporting loss of function.

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2
Pathophys.
6
Phenotypes
9
Pathograph
1
Genes
2
Medical Actions
🏷

Classifications

Harrison's Part
GENETICS ENVIRONMENT DISEASE NEUROLOGIC
⚙

Pathophysiology

2
MED17 head-module Mediator dysfunction
MED17 is a subunit of the head module of the Mediator complex, required for RNA polymerase II preinitiation. The recurrent p.Leu371Pro variant is a loss-of-function allele (it inactivated the homologous yeast SRB4 gene in complementation assays), disrupting Mediator-dependent transcription. The resulting phenotype is a severe, postnatal-onset neurodegenerative process. MED17 belongs to the group of Mediator complex-associated disease genes.
MED17 hgnc:2375 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves MED17 (hgnc:2375). hgnc:2375 is a gene from the HUGO Gene Nomenclature Committee.
transcription by RNA polymerase II GO:0006366 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves transcription by RNA polymerase II (GO:0006366). GO:0006366 is a biological process from the Gene Ontology. regulation of gene expression GO:0010468 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated regulation of gene expression (GO:0010468). GO:0010468 is a biological process from the Gene Ontology. ↕ DYSREGULATED
Downstream
Postnatal neurodegeneration and brain atrophy MED17 loss of function disrupts Mediator-dependent transcription, producing postnatal progressive microcephaly with cerebral and cerebellar atrophy.
Show evidence (1 reference)
PMID:20950787 SUPPORT In Vitro
"A corresponding mutation in the homologous S.cerevisiae gene SRB4 inactivated the protein, according to complementation assays."
Yeast complementation establishes the MED17 founder allele as loss-of-function.
Postnatal neurodegeneration and brain atrophy
Downstream of MED17 head-module dysfunction, a severe postnatal neurodegenerative process produces declining head-circumference percentiles (postnatal progressive microcephaly), marked cerebral and cerebellar atrophy with a severe myelination defect, spasticity, epilepsy, and profound psychomotor retardation.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
myelination GO:0042552 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased myelination (GO:0042552). GO:0042552 is a biological process from the Gene Ontology. ↓ DECREASED
cerebellum UBERON:0002037 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebellum (UBERON:0002037). UBERON:0002037 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Progressive microcephaly A postnatal neurodegenerative process produces declining head circumference and progressive microcephaly.
Cerebral atrophy Neurodegeneration produces marked cerebral atrophy.
Cerebellar atrophy Neurodegeneration produces marked cerebellar atrophy.
Spasticity Disrupted motor pathways produce spasticity.
Seizures Cortical dysfunction produces epilepsy.
Global developmental delay The neurodegenerative process produces profound psychomotor retardation.
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
Documents the cerebral/cerebellar atrophy and myelination defect central to the disorder.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for MED17-Related Disorder Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Musculoskeletal 1
Spasticity VERY_FREQUENT HP:0001257 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Spasticity (HP:0001257). HP:0001257 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:20950787 SUPPORT Human Clinical
"Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
Documents spasticity as an early, near-universal feature.
PMID:33756211 SUPPORT Human Clinical
"All patients had progressive spasticity and were wheelchair bound due to spastic quadriplegia."
The delineation cohort reports progressive spasticity in all patients, supporting the VERY_FREQUENT band.
Nervous System 4
Global developmental delay VERY_FREQUENT HP:0001263 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Global developmental delay (HP:0001263). HP:0001263 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:20950787 SUPPORT Human Clinical
"Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
Documents profound psychomotor retardation in all affected infants.
PMID:33756211 SUPPORT Human Clinical
"All of them eventually developed profound intellectual disability."
The delineation cohort reports profound intellectual disability in all patients, supporting the VERY_FREQUENT band.
Seizures VERY_FREQUENT HP:0001250 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:20950787 SUPPORT Human Clinical
"Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
Documents epilepsy as an early, near-universal feature.
PMID:33756211 SUPPORT Human Clinical
"Epilepsy of varied severity was present in all patients."
The delineation cohort reports epilepsy in all patients, supporting the VERY_FREQUENT band.
Cerebral atrophy HP:0002059 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cerebral atrophy (HP:0002059). HP:0002059 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
Documents cerebral atrophy as a defining imaging feature.
Cerebellar atrophy HP:0001272 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cerebellar atrophy (HP:0001272). HP:0001272 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
Documents cerebellar atrophy as a defining imaging feature.
Other 1
Progressive microcephaly HP:0000253 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Progressive microcephaly (HP:0000253). HP:0000253 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"Primary microcephaly of postnatal onset is a feature of many neurological disorders, mostly associated with mental retardation, seizures, and spasticity, and it typically carries a grave prognosis."
Documents postnatal-onset progressive microcephaly and its grave prognosis; the source does not quantify a per-feature frequency, so no band is asserted.
🧬

Genetic Associations

1
MED17 biallelic founder variant (Causative)
Gene: MED17 hgnc:2375 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MED17 (hgnc:2375). hgnc:2375 is a gene from the HUGO Gene Nomenclature Committee.
Autosomal Recessive
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"We conclude that the p. L371P mutation in MED17 is a founder mutation in the Caucasus Jewish community"
Establishes the recurrent MED17 founder allele.
💊

Medical Actions

2
Supportive Care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Supportive and palliative care, including seizure management and management of spasticity and feeding difficulties, given the grave prognosis.
Genetic Counseling
Action: Genetic CounselingNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Genetic Counseling (NCIT:C15240). NCIT:C15240 is a clinical intervention from the NCI Thesaurus. NCIT:C15240
Genetic counseling is recommended given the autosomal recessive inheritance and founder-allele population structure, with carrier testing for at-risk relatives.
Show evidence (1 reference)
PMID:20950787 SUPPORT Human Clinical
"all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families."
A shared homozygous founder allele in a defined population establishes the autosomal recessive basis that warrants carrier and recurrence-risk counseling.
📊

Prevalence

1
Caucasus Jewish
Cases In Literature <1 in 1,000,000
Ultra-rare, clustering in Caucasus-Jewish founder families carrying the recurrent p.Leu371Pro allele. A later delineation study assembled 15 patients (10 males, 5 females) from 11 families carrying the same founder allele. No population-based prevalence estimate is available.
Show evidence (2 references)
PMID:20950787 SUPPORT Human Clinical
"all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families."
Documents the founder-population structure of the defining cohort.
PMID:33756211 SUPPORT Human Clinical
"The study cohort, including the previously reported patients, comprised 10 males and 5 females from 11 families."
Documents the expanded founder-allele cohort (15 patients from 11 families), supporting the statement that additional families have been reported.
{ }

Source YAML

click to show 
name: MED17-Related Disorder
creation_date: '2026-07-31T00:00:00Z'
category: Mendelian
synonyms:
- Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly
- MCPHA
- Mental retardation, postnatal progressive microcephaly, and seizures
- MED17-related infantile cerebral and cerebellar atrophy
description: >
  MED17-related disorder (MCPHA) is a rare autosomal recessive neurodevelopmental and
  neurodegenerative disorder caused by biallelic variants in MED17, a subunit of the head module
  of the Mediator transcriptional coactivator complex, with a recurrent homozygous founder allele
  (p.Leu371Pro) in Caucasus-Jewish families. Infants are normal at birth and then develop
  postnatal progressive microcephaly, spasticity, epilepsy, and profound psychomotor retardation;
  brain MRI shows marked cerebral and cerebellar atrophy with a severe myelination defect.
  Prognosis is grave. Because MED17 acts in the constitutive head module rather than the
  dissociable kinase module, MCPHA is one of the founding recessive "core-module" MEDopathies;
  the p.L371P allele inactivated the homologous yeast gene SRB4 in complementation assays,
  supporting loss of function.
disease_term:
  preferred_term: Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly
  term:
    id: MONDO:0013351
    label: infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly
parents:
- Autosomal recessive intellectual disability
- Neurodevelopmental disorder
- Mediator complex-associated disorder
classifications:
  harrisons_chapter:
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
    evidence:
    - reference: PMID:20950787
      reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A missense mutation in one of them, MED17, segregated with the disease state in the families"
      explanation: Supports classification as a heritable autosomal recessive genetic disorder.
  - classification_value: NEUROLOGIC
    evidence:
    - reference: PMID:20950787
      reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
      explanation: Supports classification as a neurodevelopmental / neurologic (and neurodegenerative) disorder.
prevalence:
- population: Caucasus Jewish
  measure_type: CASES_IN_LITERATURE
  prevalence_class: BELOW_1_IN_1000000
  notes: >-
    Ultra-rare, clustering in Caucasus-Jewish founder families carrying the recurrent
    p.Leu371Pro allele. A later delineation study assembled 15 patients (10 males, 5 females)
    from 11 families carrying the same founder allele. No population-based prevalence
    estimate is available.
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families."
    explanation: Documents the founder-population structure of the defining cohort.
  - reference: PMID:33756211
    reference_title: "Delineation of the phenotype of MED17-related disease in Caucasus-Jewish families."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The study cohort, including the previously reported patients, comprised 10 males and 5 females from 11 families."
    explanation: Documents the expanded founder-allele cohort (15 patients from 11 families), supporting the statement that additional families have been reported.
pathophysiology:
- name: MED17 head-module Mediator dysfunction
  description: >
    MED17 is a subunit of the head module of the Mediator complex, required for RNA polymerase
    II preinitiation. The recurrent p.Leu371Pro variant is a loss-of-function allele (it
    inactivated the homologous yeast SRB4 gene in complementation assays), disrupting
    Mediator-dependent transcription. The resulting phenotype is a severe, postnatal-onset
    neurodegenerative process. MED17 belongs to the group of Mediator complex-associated
    disease genes.
  genes:
  - preferred_term: MED17
    term:
      id: hgnc:2375
      label: MED17
  biological_processes:
  - preferred_term: transcription by RNA polymerase II
    term:
      id: GO:0006366
      label: transcription by RNA polymerase II
  - preferred_term: regulation of gene expression
    term:
      id: GO:0010468
      label: regulation of gene expression
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "A corresponding mutation in the homologous S.cerevisiae gene SRB4 inactivated the protein, according to complementation assays."
    explanation: Yeast complementation establishes the MED17 founder allele as loss-of-function.
  downstream:
  - target: Postnatal neurodegeneration and brain atrophy
    description: >-
      MED17 loss of function disrupts Mediator-dependent transcription, producing postnatal
      progressive microcephaly with cerebral and cerebellar atrophy.
- name: Postnatal neurodegeneration and brain atrophy
  description: >
    Downstream of MED17 head-module dysfunction, a severe postnatal neurodegenerative process
    produces declining head-circumference percentiles (postnatal progressive microcephaly),
    marked cerebral and cerebellar atrophy with a severe myelination defect, spasticity,
    epilepsy, and profound psychomotor retardation.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  locations:
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  biological_processes:
  - preferred_term: myelination
    term:
      id: GO:0042552
      label: myelination
    modifier: DECREASED
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
    explanation: Documents the cerebral/cerebellar atrophy and myelination defect central to the disorder.
  downstream:
  - target: Progressive microcephaly
    description: A postnatal neurodegenerative process produces declining head circumference and progressive microcephaly.
  - target: Cerebral atrophy
    description: Neurodegeneration produces marked cerebral atrophy.
  - target: Cerebellar atrophy
    description: Neurodegeneration produces marked cerebellar atrophy.
  - target: Spasticity
    description: Disrupted motor pathways produce spasticity.
  - target: Seizures
    description: Cortical dysfunction produces epilepsy.
  - target: Global developmental delay
    description: The neurodegenerative process produces profound psychomotor retardation.
phenotypes:
- category: Clinical
  name: Progressive microcephaly
  description: >
    Postnatal progressive microcephaly with declining head-circumference percentiles is a
    defining feature; infants are normocephalic at birth.
  phenotype_term:
    preferred_term: Progressive microcephaly
    term:
      id: HP:0000253
      label: Progressive microcephaly
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Primary microcephaly of postnatal onset is a feature of many neurological disorders, mostly associated with mental retardation, seizures, and spasticity, and it typically carries a grave prognosis."
    explanation: Documents postnatal-onset progressive microcephaly and its grave prognosis; the source does not quantify a per-feature frequency, so no band is asserted.
- category: Clinical
  name: Global developmental delay
  frequency: VERY_FREQUENT
  description: >
    Profound psychomotor retardation is present in all affected infants.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
    explanation: Documents profound psychomotor retardation in all affected infants.
  - reference: PMID:33756211
    reference_title: "Delineation of the phenotype of MED17-related disease in Caucasus-Jewish families."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All of them eventually developed profound intellectual disability."
    explanation: The delineation cohort reports profound intellectual disability in all patients, supporting the VERY_FREQUENT band.
- category: Clinical
  name: Spasticity
  frequency: VERY_FREQUENT
  description: >
    Spasticity is present from early infancy.
  phenotype_term:
    preferred_term: Spasticity
    term:
      id: HP:0001257
      label: Spasticity
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
    explanation: Documents spasticity as an early, near-universal feature.
  - reference: PMID:33756211
    reference_title: "Delineation of the phenotype of MED17-related disease in Caucasus-Jewish families."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All patients had progressive spasticity and were wheelchair bound due to spastic quadriplegia."
    explanation: The delineation cohort reports progressive spasticity in all patients, supporting the VERY_FREQUENT band.
- category: Clinical
  name: Seizures
  frequency: VERY_FREQUENT
  description: >
    Epilepsy is present from early infancy.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five infants from four unrelated families of Caucasus Jewish origin presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation."
    explanation: Documents epilepsy as an early, near-universal feature.
  - reference: PMID:33756211
    reference_title: "Delineation of the phenotype of MED17-related disease in Caucasus-Jewish families."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Epilepsy of varied severity was present in all patients."
    explanation: The delineation cohort reports epilepsy in all patients, supporting the VERY_FREQUENT band.
- category: Clinical
  name: Cerebral atrophy
  description: >
    Marked cerebral atrophy with a severe myelination defect is seen on brain MRI.
  phenotype_term:
    preferred_term: Cerebral atrophy
    term:
      id: HP:0002059
      label: Cerebral atrophy
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
    explanation: Documents cerebral atrophy as a defining imaging feature.
- category: Clinical
  name: Cerebellar atrophy
  description: >
    Marked cerebellar atrophy is seen on brain MRI.
  phenotype_term:
    preferred_term: Cerebellar atrophy
    term:
      id: HP:0001272
      label: Cerebellar atrophy
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "homozygosity for this mutation is associated with infantile cerebral and cerebellar atrophy with poor myelination."
    explanation: Documents cerebellar atrophy as a defining imaging feature.
genetic:
- name: MED17 biallelic founder variant
  association: Causative
  gene_term:
    preferred_term: MED17
    term:
      id: hgnc:2375
      label: MED17
  inheritance:
  - name: Autosomal Recessive
    inheritance_term:
      preferred_term: Autosomal recessive inheritance
      term:
        id: HP:0000007
        label: Autosomal recessive inheritance
    evidence:
    - reference: PMID:20950787
      reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families."
      explanation: Homozygosity for the founder allele causing disease is consistent with autosomal recessive inheritance.
  features: >
    Biallelic variants; recurrent homozygous founder allele p.Leu371Pro in Caucasus-Jewish
    families, shown to be loss-of-function by yeast SRB4 complementation.
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conclude that the p. L371P mutation in MED17 is a founder mutation in the Caucasus Jewish community"
    explanation: Establishes the recurrent MED17 founder allele.
treatments:
- name: Supportive Care
  description: >
    Supportive and palliative care, including seizure management and management of spasticity
    and feeding difficulties, given the grave prognosis.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
- name: Genetic Counseling
  description: >
    Genetic counseling is recommended given the autosomal recessive inheritance and
    founder-allele population structure, with carrier testing for at-risk relatives.
  treatment_term:
    preferred_term: Genetic Counseling
    term:
      id: NCIT:C15240
      label: Genetic Counseling
  evidence:
  - reference: PMID:20950787
    reference_title: "Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "all homozygous for the p.L371P mutation and all originating from Caucasus Jewish families."
    explanation: A shared homozygous founder allele in a defined population establishes the autosomal recessive basis that warrants carrier and recurrence-risk counseling.