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Ritscher-Schinzel Syndrome

1. Disease Information

2026-06-05
Falcon MONDO:0019078 Model: Edison Scientific Literature 31 citations

1. Disease Information

1.1 Concise overview (current understanding)

Ritscher–Schinzel syndrome is a multisystem developmental disorder classically defined by a triad of craniofacial features, cerebellar anomalies, and congenital heart defects, hence “3C syndrome.” (otsuji2023clinicaldiversityand pages 1-2). In a recent mechanistic reframing, RSS is proposed to be an endosomal recycling disorder (“endosomal recyclinopathy”) arising from dysfunction of the Commander endosomal recycling pathway (kato2024thecongenitalmultiple pages 1-4).

1.2 Key identifiers and synonyms

A subset of identifiers could be extracted directly from retrieved sources (OMIM only); other identifier systems (Orphanet/ICD/MeSH/MONDO) were not present in the retrieved full texts and should be populated via the authoritative databases.

Table (click to expand)
Identifier system Code/ID Label Notes URL
OMIM MIM:220210 Ritscher-Schinzel syndrome / 3C syndrome Retrieved evidence links RSS/3C syndrome to OMIM 220210; classic disease label/synonym supported by 2015 and 2023 literature summaries and a syndrome list noting “3 C-syndrom, cranio-cerebello-cardiale Dysplasie.” (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) https://omim.org/entry/220210
OMIM MIM:300963 CCDC22-associated Ritscher-Schinzel syndrome Otsuji 2023 notes OMIM 300963 in connection with RSS via CCDC22, reflecting the X-linked form/gene-specific entry rather than the aggregate syndrome label. (otsuji2023clinicaldiversityand pages 1-2) https://omim.org/entry/300963
OMIM MIM:619135 VPS35L-associated Ritscher-Schinzel syndrome Otsuji 2023 identifies VPS35L as the “third responsible gene” for RSS and cites MIM 619135 for this gene-associated form. (otsuji2023clinicaldiversityand pages 1-2) https://omim.org/entry/619135
Synonym RSS Ritscher-Schinzel syndrome Common abbreviation used in recent peer-reviewed and preprint literature. (otsuji2023clinicaldiversityand pages 1-2, kato2024thecongenitalmultiple pages 1-4) N/A
Synonym 3C syndrome Cranio-cerebello-cardiac syndrome / cranio-cerebello-cardiac dysplasia Widely used alternative name reflecting the core triad of craniofacial, cerebellar, and cardiac abnormalities. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) N/A
Synonym 3 C syndrome Ritscher-Schinzel/3 C syndrome Variant spacing/formatting appears in the literature, especially in gene-specific CCDC22 reports. (singla2025ccdc22mutationsthat pages 10-10) N/A
Disease concept N/A Multi-system developmental disorder Recent sources describe RSS as a congenital multiple-organ malformation syndrome characterized by craniofacial, cerebellar, and cardiac defects; newer mechanistic framing is an “endosomal recyclinopathy.” (otsuji2023clinicaldiversityand pages 1-2, kato2024thecongenitalmultiple pages 1-4) N/A
Orphanet Not found in retrieved evidence To be filled from external database No ORPHA identifier was present in the retrieved evidence; verify directly in Orphanet before KB ingestion. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) https://www.orpha.net
ICD-10 / ICD-11 Not found in retrieved evidence To be filled from external database No ICD code was present in the retrieved evidence; confirm from WHO/clinical coding resources. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) https://icd.who.int/
MeSH Not found in retrieved evidence To be filled from external database No MeSH term/ID was present in the retrieved evidence; confirm in MeSH Browser. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) https://meshb.nlm.nih.gov/
MONDO Not found in retrieved evidence To be filled from external database No MONDO identifier was present in the retrieved evidence; confirm in Mondo/OBO resources. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) https://monarchinitiative.org/
Evidence provenance Aggregated disease-level literature and syndrome catalogs Not EHR-derived in retrieved evidence Available evidence comes from peer-reviewed case series/reviews and syndrome listings rather than individual EHR datasets; examples include Otsuji 2023 J Med Genet and a syndrome list containing the 220210 identifier. (hirschsprungUnknownyearsyndrome pages 7-7, otsuji2023clinicaldiversityand pages 1-2) N/A

Table: This table summarizes the disease identifiers and naming conventions for Ritscher-Schinzel syndrome based strictly on retrieved evidence. It highlights confirmed OMIM entries and synonyms while flagging ORPHA, ICD, MeSH, and MONDO as requiring direct verification from external databases.

Evidence source types represented in this report: aggregated disease-level literature (peer-reviewed research and case series; preprint cohort analyses), not EHR-derived datasets (otsuji2023clinicaldiversityand pages 1-2, kato2024thecongenitalmultiple pages 1-4).

2. Etiology

2.1 Disease causal factors

Primary cause: pathogenic variants affecting genes encoding subunits of the endosomal recycling machinery—especially the Commander pathway (Retriever + CCC complex, functionally coupled to WASH complex). This has been linked to RSS by structural biology (Commander complex structure) and by patient genetic and functional studies (healy2023structureofthe pages 1-3, otsuji2023clinicaldiversityand pages 1-2).

2.2 Risk factors

2.3 Protective factors / gene–environment interactions

No protective factors or gene–environment interactions were described in the retrieved evidence.

3. Phenotypes

3.1 Core phenotypic triad and spectrum

RSS/3C is defined by the triad: - Craniofacial anomalies (craniofacial dysmorphism/abnormal craniofacial features) (healy2023structureofthe pages 1-3, otsuji2023clinicaldiversityand pages 1-2) - Cerebellar anomalies (often described as cerebellar hypoplasia) (healy2023structureofthe pages 1-3, kato2024thecongenitalmultiple pages 66-68) - Cardiac defects (stunted cardiovascular development / congenital heart defects) (healy2023structureofthe pages 1-3, otsuji2023clinicaldiversityand pages 1-2)

Expanded multisystem involvement reported in recent sources includes renal, skeletal, hepatic, gastrointestinal, immunologic, and lipid phenotypes (kato2024thecongenitalmultiple pages 1-4, otsuji2023clinicaldiversityand pages 1-1).

3.2 Frequencies/statistics from recent/available evidence

3.3 Age of onset, severity, progression (general)

  • Onset: congenital/early-life (implied by malformations; prenatal/infant presentations are common) (kato2024thecongenitalmultiple pages 1-4).
  • Severity/expressivity: variable across genes and even within the same gene; VPS35L-associated RSS shows diverse severity, and milder phenotypes correlated with relatively higher VPS35L protein levels in patient-derived cells (otsuji2023clinicaldiversityand pages 1-1).
  • Course: chronic/lifelong multisystem disease; early mortality occurs in severe forms (e.g., biallelic COMMD4-L41R family with deaths ages 0–5 in 2024 preprint cohort) (kato2024thecongenitalmultiple pages 16-19).

3.4 Suggested HPO terms (examples; not exhaustive)

(These are ontology suggestions based on the phenotypes explicitly described in retrieved sources.) - Abnormal craniofacial morphology (e.g., Abnormal facial shape; Craniofacial dysmorphism) (healy2023structureofthe pages 1-3) - Cerebellar hypoplasia (healy2023structureofthe pages 1-3) - Congenital heart defect (otsuji2023clinicaldiversityand pages 1-2) - Global developmental delay / Intellectual disability (kolanczyk2015missensevariantin pages 1-2) - Proteinuria (otsuji2023clinicaldiversityand pages 1-1) - Hypercholesterolemia (otsuji2023clinicaldiversityand pages 1-1) - Hypogammaglobulinemia (otsuji2023clinicaldiversityand pages 1-1) - Intestinal lymphangiectasia (otsuji2023clinicaldiversityand pages 1-1)

3.5 Quality-of-life impact

Direct patient-reported QoL instruments (EQ-5D/SF-36/PROMIS) were not described in retrieved evidence; however, neurodevelopmental impairment and multi-organ morbidity (cardiac, renal, GI, immunologic) are expected to substantially affect daily function (kato2024thecongenitalmultiple pages 66-68).

4. Genetic / Molecular Information

4.1 Causal genes and inheritance patterns (current)

Recent literature supports RSS as a disorder of Commander/WASH pathway genes. Key genes with disease association in retrieved evidence: - WASHC5 (WASH complex; RSS/3C association with biallelic loss-of-function summarized in 2024 synthesis) (kato2024thecongenitalmultiple pages 66-68) - CCDC22 (CCC complex; X-linked/hemizygous form; overlaps with XLID and RSS features) (otsuji2023clinicaldiversityand pages 1-2) - VPS35L (Retriever complex; biallelic; “third responsible gene” for RSS after WASHC5 and CCDC22) (otsuji2023clinicaldiversityand pages 1-1)

A 2024 cohort/mechanistic preprint proposed additional candidate/causal genes within the Commander pathway: - COMMD4, COMMD9, CCDC93 (CCC complex components; biallelic) (kato2024thecongenitalmultiple pages 6-9).

Table (click to expand)
Gene (HGNC symbol) Protein/complex Inheritance pattern reported Variant types (general) Key clinical notes/complications Key supporting recent sources with publication year and URL
WASHC5 Strumpellin; core WASH complex subunit functionally linked to Commander-mediated recycling Autosomal recessive for RSS/3C in retrieved evidence; biallelic loss-of-function reported General loss-of-function; splice/disruptive variants reported in RSS literature summaries Classic RSS/3C phenotype with developmental delay, cerebellar hypoplasia, cardiac abnormalities; 2024 summary table notes developmental delay in 11/11 and cardiac abnormalities in 7/11 WASHC5-associated cases; mechanism tied to reduced recycling of surface cargo proteins (kato2024thecongenitalmultiple pages 66-68, kato2024thecongenitalmultiple pages 14-16, otsuji2023clinicaldiversityand pages 1-2) Kato et al., 2024, medRxiv, https://doi.org/10.1101/2024.08.17.24311658; Otsuji et al., 2023, J Med Genet, https://doi.org/10.1136/jmg-2022-108602 (kato2024thecongenitalmultiple pages 66-68, kato2024thecongenitalmultiple pages 14-16, otsuji2023clinicaldiversityand pages 1-2)
CCDC22 CCC complex subunit within Commander X-linked / hemizygous form reported; gene-specific RSS/3C overlap with XLID Missense and other variants that disrupt CCC assembly/COMMD binding; loss-of-function/functional impairment reported RSS/3C with craniofacial, cerebellar, cardiac, and neurodevelopmental involvement; some attenuated phenotypes may lack major cardiac/neuroanatomical abnormalities; CCDC22 dysfunction perturbs CCC assembly and Commander function (otsuji2023clinicaldiversityand pages 1-2, singla2025ccdc22mutationsthat pages 10-10, singla2025ccdc22mutationsthat pages 1-2) Healy et al., 2023, Cell, https://doi.org/10.1016/j.cell.2023.04.003; Singla et al., 2025, BMC Med Genomics, https://doi.org/10.1186/s12920-025-02168-7; Otsuji et al., 2023, J Med Genet, https://doi.org/10.1136/jmg-2022-108602 (otsuji2023clinicaldiversityand pages 1-2, singla2025ccdc22mutationsthat pages 10-10, singla2025ccdc22mutationsthat pages 1-2)
VPS35L Retriever subunit (with VPS26C and VPS29) within Commander Autosomal recessive / biallelic Biallelic pathogenic variants including truncating, splice-altering, in-frame deletion, and missense alleles with reduced protein stability/function Distinct VPS35L-associated RSS spectrum with variable severity; novel 2023 complications include hypercholesterolaemia, hypogammaglobulinaemia, intestinal lymphangiectasia, and proteinuria; mechanism includes reduced cell-surface LRP1/LDLR and reduced LDL uptake (otsuji2023clinicaldiversityand pages 1-1, otsuji2023clinicaldiversityand pages 5-6, otsuji2023clinicaldiversityand pages 8-8) Otsuji et al., 2023, J Med Genet, https://doi.org/10.1136/jmg-2022-108602; Healy et al., 2023, Cell, https://doi.org/10.1016/j.cell.2023.04.003 (otsuji2023clinicaldiversityand pages 1-1, otsuji2023clinicaldiversityand pages 5-6, healy2023structureofthe pages 1-3, otsuji2023clinicaldiversityand pages 8-8)
COMMD4 CCC complex subunit; Commander-associated Autosomal recessive / biallelic in 2024 preprint cohort Biallelic pathogenic variants; severe COMMD4-L41R genotype highlighted Newly proposed RSS gene; associated with severe multisystem disease and early childhood death (ages 0–5) in reported family; functional studies suggest major Commander cargo-recycling defects (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9) Kato et al., 2024, medRxiv, https://doi.org/10.1101/2024.08.17.24311658 (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9)
COMMD9 CCC complex subunit; Commander-associated Autosomal recessive / biallelic in 2024 preprint cohort Biallelic pathogenic/truncating variants reported in candidate-gene expansion study Newly proposed RSS gene; functional data indicate milder cargo-trafficking defects than COMMD4 or CCDC93 loss, suggesting residual pathway activity may moderate severity (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9) Kato et al., 2024, medRxiv, https://doi.org/10.1101/2024.08.17.24311658 (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9)
CCDC93 CCC complex scaffold subunit within Commander Autosomal recessive / biallelic in 2024 preprint cohort Biallelic pathogenic variants causing loss of CCC/Commander function Newly proposed RSS gene; linked to dysgenic corpus callosum, cerebellar abnormalities, limb/nail anomalies, and broader multisystem RSS manifestations; knockout/cell studies support defective endosomal recycling (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9) Kato et al., 2024, medRxiv, https://doi.org/10.1101/2024.08.17.24311658 (kato2024thecongenitalmultiple pages 16-19, kato2024thecongenitalmultiple pages 6-9)
Pathway-level note Commander = Retriever + CCC, acting with the WASH complex in SNX17-dependent endosomal recycling Not applicable Not applicable Retrieved evidence supports RSS as an endosomal recyclinopathy caused by impaired retrieval/recycling of membrane cargoes including integrins and lipoprotein receptors; this provides a unifying mechanism across WASHC5, CCDC22, VPS35L, and newly proposed CCC-gene cases (kato2024thecongenitalmultiple pages 14-16, healy2023structureofthe pages 1-3, kato2024thecongenitalmultiple pages 4-6, kato2024thecongenitalmultiple pages 6-9) Healy et al., 2023, Cell, https://doi.org/10.1016/j.cell.2023.04.003; Kato et al., 2024, medRxiv, https://doi.org/10.1101/2024.08.17.24311658; Otsuji et al., 2023, J Med Genet, https://doi.org/10.1136/jmg-2022-108602 (kato2024thecongenitalmultiple pages 14-16, healy2023structureofthe pages 1-3, kato2024thecongenitalmultiple pages 4-6, kato2024thecongenitalmultiple pages 6-9)

Table: This table summarizes the currently supported and newly proposed genetic causes of Ritscher-Schinzel syndrome/3C syndrome, emphasizing the shared Commander-Retriever-CCC-WASH endosomal recycling mechanism. It is useful for quickly comparing inheritance, variant classes, and distinctive complications across genes.

4.2 Pathogenic variant classes and functional consequences

Across genes, reported variants are primarily loss-of-function or complex-destabilizing alleles (frameshift/truncating, splice-altering, in-frame deletions, or missense variants that impair complex assembly/interactions) resulting in reduced endosomal recycling capacity and decreased cell-surface expression of key cargos (otsuji2023clinicaldiversityand pages 5-6, kato2024thecongenitalmultiple pages 6-9).

4.3 Population allele frequencies

Population allele frequency data (e.g., gnomAD) were not provided in the retrieved sources.

4.4 Modifier genes / epigenetic information / chromosomal abnormalities

No specific modifier genes or epigenetic signatures were described in the retrieved evidence. Chromosomal microarray (array-CGH) was used diagnostically in at least one CCDC22-related study, but this is a testing modality rather than a recurrent chromosomal cause in the retrieved evidence (kolanczyk2015missensevariantin pages 1-2).

5. Environmental Information

No non-genetic environmental contributors, lifestyle associations, or infectious triggers were described in the retrieved evidence, consistent with a congenital Mendelian malformation syndrome.

6. Mechanism / Pathophysiology

6.1 Key concept: RSS as an “endosomal recyclinopathy”

A 2024 cohort/mechanistic study explicitly frames RSS as an endosomal recycling disorder: it “establishes RSS as a 'recyclinopathy' that arises from a dysfunction in the Commander endosomal recycling pathway” (kato2024thecongenitalmultiple pages 1-4). Commander is required for endosomal recycling of diverse transmembrane cargos and is mutated in RSS (healy2023structureofthe pages 1-3).

6.2 Molecular pathway description (Commander / SNX17–Retriever–CCC–WASH)

  • Commander architecture: a 16-subunit assembly comprising two subassemblies—Retriever (VPS35L, VPS26C, VPS29) and CCC complex (COMMD proteins with CCDC22 and CCDC93) (healy2023structureofthe pages 1-3).
  • Functional role: Commander regulates retromer-independent retrieval and recycling of many proteins, including integrins and lipoprotein receptors (healy2023structureofthe pages 1-3).
  • Disease mechanism: impairment of this recycling pathway reduces cell-surface expression of integral membrane proteins, providing a mechanistic basis for multisystem developmental defects (otsuji2023clinicaldiversityand pages 1-2).

6.3 Mechanistic links to key complications

  • Hypercholesterolemia: VPS35L ablation decreases surface LRP1 and LDLR, reducing LDL uptake; authors propose this as a molecular mechanism for hypercholesterolemia in VPS35L-associated RSS (otsuji2023clinicaldiversityand pages 1-1). Structural work also notes Commander mutations can lead to hypercholesterolemia via reduced trafficking of LDL receptors (healy2023structureofthe pages 1-3).
  • Proteinuria / renal phenotype: Commander pathway perturbation is linked to altered recycling of kidney-relevant receptors (e.g., LRP2) and proteinuria as a clinical phenotype (kato2024thecongenitalmultiple pages 6-9).

6.4 Suggested GO biological process terms (examples)

Ontology suggestions aligned with the mechanistic evidence: - Endosomal transport / endosome-to-plasma membrane recycling (Commander-dependent recycling) (healy2023structureofthe pages 1-3) - Receptor-mediated endocytosis / receptor recycling (LRP1/LDLR trafficking) (otsuji2023clinicaldiversityand pages 1-1) - Actin filament organization (endosomal branched actin) (WASH complex functional coupling to recycling) (otsuji2023clinicaldiversityand pages 1-2)

6.5 Suggested Cell Ontology (CL) cell types (examples)

Based on tissues/organs implicated by cargo and phenotype: - Hepatocyte (lipoprotein receptor recycling and cholesterol phenotype) (otsuji2023clinicaldiversityand pages 1-1) - Renal proximal tubule epithelial cell (proteinuria/LRP2-related proximal tubular reabsorption context) (kato2024thecongenitalmultiple pages 6-9) - Neurons (synaptic cargo defects and neurodevelopmental impairment) (kato2024thecongenitalmultiple pages 14-16)

7. Anatomical Structures Affected

7.1 Organ/system level

7.2 Suggested UBERON terms (examples)

8. Temporal Development

  • Onset: congenital / infancy (malformation syndrome) (kato2024thecongenitalmultiple pages 1-4).
  • Critical periods: embryonic development/organogenesis implied by congenital structural anomalies.
  • Progression: variable; some complications (e.g., lipid abnormalities, immunodeficiency, proteinuria) emerge with postnatal physiology and require longitudinal monitoring (otsuji2023clinicaldiversityand pages 1-1).

9. Inheritance and Population

9.1 Inheritance

9.2 Epidemiology

Prevalence/incidence, geographic distribution, and sex ratio were not present in the retrieved evidence and should be obtained from Orphanet and registry-based sources.

10. Diagnostics

10.1 Clinical recognition and imaging

Diagnosis is typically initiated by recognizing the 3C triad (craniofacial, cerebellar, cardiac) (otsuji2023clinicaldiversityand pages 1-2), followed by: - Brain MRI focused on posterior fossa/cerebellar anomalies (singla2025ccdc22mutationsthat pages 4-5) - Echocardiography/cardiac evaluation for congenital heart disease (singla2025ccdc22mutationsthat pages 1-2)

10.2 Genetic testing (real-world implementations)

A representative diagnostic workflow from a CCDC22-associated report included: - Chromosomal microarray (array-CGH) - Whole-exome sequencing (WES) with standard filtering against population databases and internal controls, followed by confirmatory and functional studies (e.g., western blot) (kolanczyk2015missensevariantin pages 1-2).

Given the expanding gene set, contemporary practice is well aligned with exome/genome-first testing or multigene panels targeting Commander/WASH pathway genes (WASHC5, CCDC22, VPS35L, and potentially CCC subunits as evidence matures) (kato2024thecongenitalmultiple pages 6-9).

10.3 Differential diagnosis

Not exhaustively enumerated in retrieved evidence. In practice, major differentials include other syndromic congenital heart + posterior fossa malformation disorders, and other endosomal trafficking disorders; gene-centric testing reduces diagnostic ambiguity (otsuji2023clinicaldiversityand pages 1-2).

11. Outcome / Prognosis

Outcomes are variable and depend on gene and severity of organ involvement. - Early mortality: reported in severe biallelic CCC-gene cases (e.g., COMMD4-L41R family with deaths ages 0–5) (kato2024thecongenitalmultiple pages 16-19). - Ongoing morbidity: neurodevelopmental impairment, congenital heart disease, renal proteinuria, lipid abnormalities, and immunologic complications may require chronic follow-up (otsuji2023clinicaldiversityand pages 1-1).

No formal survival curves or life expectancy estimates were present in retrieved evidence.

12. Treatment

No disease-modifying therapy is established in the retrieved evidence; management is multidisciplinary supportive care.

12.1 Organ-directed management (examples documented)

12.2 Suggested MAXO terms (examples)

No clinical trials specific to RSS were identified in retrieved evidence.

13. Prevention

Primary prevention is not applicable in the usual environmental sense for a Mendelian disorder; prevention focuses on genetic counseling and reproductive options (carrier testing in autosomal recessive families; X-linked counseling in CCDC22 families) (kolanczyk2015missensevariantin pages 1-2, otsuji2023clinicaldiversityand pages 1-1).

14. Other Species / Natural Disease

No naturally occurring non-human disease analogs were identified in the retrieved evidence.

15. Model Organisms

A mouse model was used to probe pathophysiology: - Vps35l conditional knockout in Nestin-lineage (Vps35l-cKONestin) showed strong neurodevelopmental phenotypes; notably ~30% (23/72) had profound hydrocephalus, alongside growth impairment, behavioral problems, and high mortality (kato2024thecongenitalmultiple pages 14-16).

This supports causal links between Retriever/Commander dysfunction and neurodevelopmental structural phenotypes.

Visual evidence (figures)

Structural studies directly connect RSS/XLID mutations to the Commander complex architecture. - Commander/Retriever/CCC subunit schematic and mutation mapping onto the structural model are shown in extracted figures from Healy et al. (Cell 2023) (healy2023structureofthe media 9aee47de, healy2023structureofthe media 5bc4c3b6, healy2023structureofthe media 274803a4).

Expert synthesis and interpretation (authoritative-source analysis)

Recent authoritative work supports a unifying concept: RSS is best understood as a developmental “recyclinopathy” caused by impaired SNX17–Retriever–CCC–WASH endosomal recycling, leading to reduced cell-surface presentation of tissue-critical receptors and adhesion molecules (kato2024thecongenitalmultiple pages 1-4, otsuji2023clinicaldiversityand pages 1-2). This framework explains why seemingly disparate features (cardiac malformations, cerebellar hypoplasia, renal proteinuria, lipid abnormalities, and immunologic/GI complications) can co-occur, and it predicts that ongoing gene discovery will likely continue within the Commander pathway and its regulators/cargo adaptors (kato2024thecongenitalmultiple pages 6-9).

Notes on citation requirements and limitations

  • PMIDs: Not available from the retrieved full-text evidence snippets for the key 2023–2024 sources used here (Cell 2023; J Med Genet 2023; medRxiv 2024). The report therefore cites DOIs and journal/preprint URLs.
  • Orphanet/ICD/MeSH/MONDO identifiers and epidemiology: Not found in retrieved full texts and should be filled via direct database queries.

Key references (recent prioritized)

References

  1. (otsuji2023clinicaldiversityand pages 1-2): Shiomi Otsuji, Yosuke Nishio, Maki Tsujita, Marlene Rio, Céline Huber, Carlos Antón-Plágaro, Seiji Mizuno, Yoshihiko Kawano, Satoko Miyatake, Marleen Simon, Ellen van Binsbergen, Richard H van Jaarsveld, Naomichi Matsumoto, Valerie Cormier-Daire, Peter J.Cullen, Shinji Saitoh, and Kohji Kato. Clinical diversity and molecular mechanism of vps35l-associated ritscher-schinzel syndrome. Journal of Medical Genetics, 60:359-367, Sep 2023. URL: https://doi.org/10.1136/jmg-2022-108602, doi:10.1136/jmg-2022-108602. This article has 29 citations and is from a domain leading peer-reviewed journal.

  2. (hirschsprungUnknownyearsyndrome pages 7-7): M Hirschsprung. Syndrome. Unknown journal, Unknown year.

  3. (kato2024thecongenitalmultiple pages 1-4): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  4. (singla2025ccdc22mutationsthat pages 10-10): Amika Singla, Carolyn Rogers, Mary-Joe Touma, Yassin El-Najjar, Alison Colley, Daniel J. Boesch, Daniel D. Billadeau, Jozef Gecz, Baoyu Chen, and Ezra Burstein. Ccdc22 mutations that impair commd binding cause attenuated 3c/ritscher-schinzel syndrome. BMC Medical Genomics, May 2025. URL: https://doi.org/10.1186/s12920-025-02168-7, doi:10.1186/s12920-025-02168-7. This article has 1 citations and is from a peer-reviewed journal.

  5. (healy2023structureofthe pages 1-3): Michael D. Healy, Kerrie E. McNally, Rebeka Butkovič, Molly Chilton, Kohji Kato, Joanna Sacharz, Calum McConville, Edmund R.R. Moody, Shrestha Shaw, Vicente J. Planelles-Herrero, Sathish K.N. Yadav, Jennifer Ross, Ufuk Borucu, Catherine S. Palmer, Kai-En Chen, Tristan I. Croll, Ryan J. Hall, Nikeisha J. Caruana, Rajesh Ghai, Thi H.D. Nguyen, Kate J. Heesom, Shinji Saitoh, Imre Berger, Christiane Schaffitzel, Tom A. Williams, David A. Stroud, Emmanuel Derivery, Brett M. Collins, and Peter J. Cullen. Structure of the endosomal commander complex linked to ritscher-schinzel syndrome. Cell, 186:2219-2237.e29, May 2023. URL: https://doi.org/10.1016/j.cell.2023.04.003, doi:10.1016/j.cell.2023.04.003. This article has 88 citations and is from a highest quality peer-reviewed journal.

  6. (otsuji2023clinicaldiversityand pages 1-1): Shiomi Otsuji, Yosuke Nishio, Maki Tsujita, Marlene Rio, Céline Huber, Carlos Antón-Plágaro, Seiji Mizuno, Yoshihiko Kawano, Satoko Miyatake, Marleen Simon, Ellen van Binsbergen, Richard H van Jaarsveld, Naomichi Matsumoto, Valerie Cormier-Daire, Peter J.Cullen, Shinji Saitoh, and Kohji Kato. Clinical diversity and molecular mechanism of vps35l-associated ritscher-schinzel syndrome. Journal of Medical Genetics, 60:359-367, Sep 2023. URL: https://doi.org/10.1136/jmg-2022-108602, doi:10.1136/jmg-2022-108602. This article has 29 citations and is from a domain leading peer-reviewed journal.

  7. (kato2024thecongenitalmultiple pages 66-68): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  8. (kolanczyk2015missensevariantin pages 1-2): Mateusz Kolanczyk, Peter Krawitz, Jochen Hecht, Anna Hupalowska, Marta Miaczynska, Katrin Marschner, Claire Schlack, Denise Emmerich, Karolina Kobus, Uwe Kornak, Peter N Robinson, Barbara Plecko, Gernot Grangl, Sabine Uhrig, Stefan Mundlos, and Denise Horn. Missense variant in ccdc22 causes x-linked recessive intellectual disability with features of ritscher-schinzel/3c syndrome. European Journal of Human Genetics, 23:633-638, Jun 2015. URL: https://doi.org/10.1038/ejhg.2014.109, doi:10.1038/ejhg.2014.109. This article has 88 citations and is from a domain leading peer-reviewed journal.

  9. (kato2024thecongenitalmultiple pages 16-19): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  10. (kato2024thecongenitalmultiple pages 6-9): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  11. (kato2024thecongenitalmultiple pages 14-16): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  12. (singla2025ccdc22mutationsthat pages 1-2): Amika Singla, Carolyn Rogers, Mary-Joe Touma, Yassin El-Najjar, Alison Colley, Daniel J. Boesch, Daniel D. Billadeau, Jozef Gecz, Baoyu Chen, and Ezra Burstein. Ccdc22 mutations that impair commd binding cause attenuated 3c/ritscher-schinzel syndrome. BMC Medical Genomics, May 2025. URL: https://doi.org/10.1186/s12920-025-02168-7, doi:10.1186/s12920-025-02168-7. This article has 1 citations and is from a peer-reviewed journal.

  13. (otsuji2023clinicaldiversityand pages 5-6): Shiomi Otsuji, Yosuke Nishio, Maki Tsujita, Marlene Rio, Céline Huber, Carlos Antón-Plágaro, Seiji Mizuno, Yoshihiko Kawano, Satoko Miyatake, Marleen Simon, Ellen van Binsbergen, Richard H van Jaarsveld, Naomichi Matsumoto, Valerie Cormier-Daire, Peter J.Cullen, Shinji Saitoh, and Kohji Kato. Clinical diversity and molecular mechanism of vps35l-associated ritscher-schinzel syndrome. Journal of Medical Genetics, 60:359-367, Sep 2023. URL: https://doi.org/10.1136/jmg-2022-108602, doi:10.1136/jmg-2022-108602. This article has 29 citations and is from a domain leading peer-reviewed journal.

  14. (otsuji2023clinicaldiversityand pages 8-8): Shiomi Otsuji, Yosuke Nishio, Maki Tsujita, Marlene Rio, Céline Huber, Carlos Antón-Plágaro, Seiji Mizuno, Yoshihiko Kawano, Satoko Miyatake, Marleen Simon, Ellen van Binsbergen, Richard H van Jaarsveld, Naomichi Matsumoto, Valerie Cormier-Daire, Peter J.Cullen, Shinji Saitoh, and Kohji Kato. Clinical diversity and molecular mechanism of vps35l-associated ritscher-schinzel syndrome. Journal of Medical Genetics, 60:359-367, Sep 2023. URL: https://doi.org/10.1136/jmg-2022-108602, doi:10.1136/jmg-2022-108602. This article has 29 citations and is from a domain leading peer-reviewed journal.

  15. (kato2024thecongenitalmultiple pages 4-6): Kohji Kato, Yosuke Nishio, Kirsty J McMillan, Aljazi Al-Maraghi, Hester Y Kroes, Mohamed S Abdel-Hamid, Emma Jones, Shrestha Shaw, Aya Yoshida, Shiomi Otsuji, Yuka Murofushi, Waleed H. O. Aamer, Ajaz A Bhat, Jehan AlRayahi, Ammira Al-Shabeeb Akil, Ellen van Binsbergen, Etienne J Janssen, Hisashi Oishi, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Akihiko Saito, Mitsuharu Hattori, Yoshihiko Kawano, Philip A Lewis, Kate J Heesom, Takeshi Takarada, Kazunobu Sawamoto, Masaki Matsushita, Tomoo Ogi, Rebeka Butkovic, Chris Danson, Kevin A Wilkinson, Khalid A Fakhro, Maha S Zaki, Shinji Saitoh, and Peter J Cullen. The congenital multiple organ malformation syndrome, ritscher-schinzel syndrome is an endosomal recyclinopathy. MedRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.17.24311658, doi:10.1101/2024.08.17.24311658. This article has 2 citations.

  16. (singla2025ccdc22mutationsthat pages 4-5): Amika Singla, Carolyn Rogers, Mary-Joe Touma, Yassin El-Najjar, Alison Colley, Daniel J. Boesch, Daniel D. Billadeau, Jozef Gecz, Baoyu Chen, and Ezra Burstein. Ccdc22 mutations that impair commd binding cause attenuated 3c/ritscher-schinzel syndrome. BMC Medical Genomics, May 2025. URL: https://doi.org/10.1186/s12920-025-02168-7, doi:10.1186/s12920-025-02168-7. This article has 1 citations and is from a peer-reviewed journal.

  17. (healy2023structureofthe media 9aee47de): Michael D. Healy, Kerrie E. McNally, Rebeka Butkovič, Molly Chilton, Kohji Kato, Joanna Sacharz, Calum McConville, Edmund R.R. Moody, Shrestha Shaw, Vicente J. Planelles-Herrero, Sathish K.N. Yadav, Jennifer Ross, Ufuk Borucu, Catherine S. Palmer, Kai-En Chen, Tristan I. Croll, Ryan J. Hall, Nikeisha J. Caruana, Rajesh Ghai, Thi H.D. Nguyen, Kate J. Heesom, Shinji Saitoh, Imre Berger, Christiane Schaffitzel, Tom A. Williams, David A. Stroud, Emmanuel Derivery, Brett M. Collins, and Peter J. Cullen. Structure of the endosomal commander complex linked to ritscher-schinzel syndrome. Cell, 186:2219-2237.e29, May 2023. URL: https://doi.org/10.1016/j.cell.2023.04.003, doi:10.1016/j.cell.2023.04.003. This article has 88 citations and is from a highest quality peer-reviewed journal.

  18. (healy2023structureofthe media 5bc4c3b6): Michael D. Healy, Kerrie E. McNally, Rebeka Butkovič, Molly Chilton, Kohji Kato, Joanna Sacharz, Calum McConville, Edmund R.R. Moody, Shrestha Shaw, Vicente J. Planelles-Herrero, Sathish K.N. Yadav, Jennifer Ross, Ufuk Borucu, Catherine S. Palmer, Kai-En Chen, Tristan I. Croll, Ryan J. Hall, Nikeisha J. Caruana, Rajesh Ghai, Thi H.D. Nguyen, Kate J. Heesom, Shinji Saitoh, Imre Berger, Christiane Schaffitzel, Tom A. Williams, David A. Stroud, Emmanuel Derivery, Brett M. Collins, and Peter J. Cullen. Structure of the endosomal commander complex linked to ritscher-schinzel syndrome. Cell, 186:2219-2237.e29, May 2023. URL: https://doi.org/10.1016/j.cell.2023.04.003, doi:10.1016/j.cell.2023.04.003. This article has 88 citations and is from a highest quality peer-reviewed journal.

  19. (healy2023structureofthe media 274803a4): Michael D. Healy, Kerrie E. McNally, Rebeka Butkovič, Molly Chilton, Kohji Kato, Joanna Sacharz, Calum McConville, Edmund R.R. Moody, Shrestha Shaw, Vicente J. Planelles-Herrero, Sathish K.N. Yadav, Jennifer Ross, Ufuk Borucu, Catherine S. Palmer, Kai-En Chen, Tristan I. Croll, Ryan J. Hall, Nikeisha J. Caruana, Rajesh Ghai, Thi H.D. Nguyen, Kate J. Heesom, Shinji Saitoh, Imre Berger, Christiane Schaffitzel, Tom A. Williams, David A. Stroud, Emmanuel Derivery, Brett M. Collins, and Peter J. Cullen. Structure of the endosomal commander complex linked to ritscher-schinzel syndrome. Cell, 186:2219-2237.e29, May 2023. URL: https://doi.org/10.1016/j.cell.2023.04.003, doi:10.1016/j.cell.2023.04.003. This article has 88 citations and is from a highest quality peer-reviewed journal.

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