Mesomelia-Synostoses Syndrome

🏷

Classifications

Harrison's Part

ISDS Skeletal Nosology

👪

Inheritance

1

Autosomal dominant HP:0000006

Autosomal dominant, from heterozygous deletion of the 8q13 interval. The deletions are non-recurrent — breakpoint sequencing in two families showed they do not arise from low-copy-repeat-mediated recombination — so each is a distinct event rather than a common rearrangement hotspot product.

Autosomal dominant inheritance

Show evidence (2 references)

PMID:20602915 SUPPORT Human Clinical

"Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations."

States the inheritance mode together with the defining features.

PMID:20602915 SUPPORT Human Clinical

"Breakpoint sequence analyses performed in two families showed nonrecurrent deletions."

Supports the non-recurrent nature of the deletions.

?

Discussions and Knowledge Gaps

1

Is SULF1 haploinsufficiency alone sufficient to cause mesomelia-synostoses syndrome, or is co-deletion of SLCO5A1 (or a position effect) genuinely required?

KNOWLEDGE GAP mss_two_gene_requirement

Attached to

pathophysiology#8q13 Contiguous Deletion of SULF1 and SLCO5A1

Every reported patient has both genes deleted, so the two-gene hypothesis has never been tested against the one-gene alternative in humans. The question decides whether an isolated SULF1 loss-of-function variant found incidentally should be reported as causal for this syndrome — a question a diagnostic laboratory will eventually face — and it is answerable either by a patient with a smaller deletion or by a single-gene mouse model.

⚙

Pathophysiology

3

8q13 Contiguous Deletion of SULF1 and SLCO5A1

Array CGH found an interstitial 8q13 deletion in every patient. The deletions differ in size but converge on the same two-gene content, which is what identified the interval. Because no patient has been reported with a lesion in only one of the two genes, the deletion is curated here as the unit of causation, with the relative contributions of the two genes left open.

SULF1 hgnc:20391 SLCO5A1 hgnc:19046

Genetic context SULF1 hgnc:20391 SLCO5A1 hgnc:19046 allele_type: interstitial 8q13 deletion of 582-738 kb zygosity: HETEROZYGOUS functional_impact_category: LOSS_OF_FUNCTION

Downstream

Loss of Heparan Sulfate 6-O-Endosulfatase Activity SULF1 haploinsufficiency follows directly from the deletion.

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1, encoding the heparan sulfate 6-O-endosulfatase 1, and SLCO5A1, encoding the solute carrier organic anion transporter family member 5A1."

Establishes the deletion interval and its exact two-gene content.

Loss of Heparan Sulfate 6-O-Endosulfatase Activity

SULF1 removes 6-O-sulfate groups from heparan sulfate proteoglycans at the cell surface, and that sulfation pattern determines how tightly heparan sulfate binds and sequesters the growth factors — Wnt, FGF, BMP, hedgehog — that pattern the skeleton. Losing an endosulfatase therefore changes growth factor availability rather than any structural protein. The expression data point the same way: SULF1 transcripts are highest in human osteoblasts and cartilage, while its co-deleted neighbour is a brain- and heart-expressed transporter of unknown function.

glycosaminoglycan metabolic process GO:0030203 ↓ DECREASED

heparan sulfate 6-O-endosulfatase activity GO:0008201 ↓ DECREASED

Downstream

Mesomelic Shortening with Acral Synostoses Which growth-factor pathway mediates the skeletal phenotype has not been identified.

Show evidence (3 references)

PMID:20602915 SUPPORT Human Clinical

"SULF1 acts as a regulator of numerous growth factors in skeletal embryonic development whereas the function of SLCO5A1 is yet unknown."

Establishes SULF1's role as a growth-factor regulator in skeletal development and the absence of any known SLCO5A1 function.

PMID:20602915 SUPPORT Human Clinical

"Real-time quantitative RT-PCR analysis showed the highest levels of SULF1 transcripts in human osteoblasts and cartilage whereas SLCO5A1 was highly expressed in human fetal and adult brain and heart."

The tissue-expression argument that makes SULF1 the better candidate of the two co-deleted genes.

PMID:20602915 SUPPORT Human Clinical

"Our results strongly suggest that haploinsufficiency of SULF1 contributes to this mesomelic chondrodysplasia, highlighting the critical role of endosulfatase in human skeletal development."

The authors' own conclusion, stated as "strongly suggest" and "contributes" rather than as sufficiency — which is why this node does not claim SULF1 loss alone explains the disorder.

Mesomelic Shortening with Acral Synostoses

The clinical endpoint: mesomelic limb shortening together with acral synostoses and additional congenital malformations. The pairing of mesomelia with synostosis is the recognizable signature, and it is shared with the HOXD-related Kantaputra type, which reaches the same combination by a completely different route.

Downstream

Mesomelic Limb Shortening Loss of endosulfatase editing changes growth-factor availability in the developing zeugopod.

Acral Synostoses Heparan sulfate sulfation state governs the growth-factor gradients that separate adjacent skeletal elements, so losing that control is a plausible route to failed segmentation. Which growth factor mediates it is not established.

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations"

Gives the defining clinical triad this node represents.

⬡

Pathograph

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

●

Phenotypes

2

Mesomelic Limb Shortening VERY_FREQUENT Skeletal HP:0003027

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations"

Mesomelic limb shortening is the first of the defining features.

Acral Synostoses VERY_FREQUENT Skeletal HP:0005048

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations"

Establishes acral synostoses as a defining feature. The abstract does not say which bones fuse, so the HP binding to carpal synostosis is the closest available term rather than a stated finding, and the evidence is PARTIAL.

🧬

Genetic Associations

2

SULF1

Gene: SULF1 hgnc:20391 relationship_type: CAUSATIVE

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"Our results strongly suggest that haploinsufficiency of SULF1 contributes to this mesomelic chondrodysplasia, highlighting the critical role of endosulfatase in human skeletal development."

The authors' attribution of the skeletal phenotype primarily to SULF1 haploinsufficiency.

SLCO5A1

Gene: SLCO5A1 hgnc:19046 relationship_type: COOPERATING

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"we suggest that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS"

The proposal that SLCO5A1 co-haploinsufficiency may be required, stated as a suggestion and with an explicit alternative, which is why this is COOPERATING and PARTIAL.

🔬

Diagnosis

1

Copy-Number Analysis of 8q13

Confirmed by demonstrating an interstitial 8q13 deletion encompassing SULF1 and SLCO5A1. Array CGH is the assay that identified the interval and remains the appropriate first-line test; the deletions are non-recurrent, so there is no single breakpoint-specific assay to use instead.

genetic testing NCIT:C15709

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"By using whole-genome oligonucleotide array CGH, we have identified an interstitial deletion at 8q13 in all patients."

Names the assay and its yield in the defining series.

📊

Prevalence

1

Worldwide

Cases In Literature Ultra Rare

Five patients in four unrelated families at the time the molecular cause was identified. No denominator-based estimate exists.

Show evidence (1 reference)

PMID:20602915 SUPPORT Human Clinical

"So far, five patients in four unrelated families have been reported worldwide with MMS."

Gives the cumulative case count, the basis for the ULTRA_RARE band.

🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Mesomelia-Synostoses Syndrome:

Mesomelic dysplasia, Kantaputra type

Overlapping Features The other group-15 disorder that pairs mesomelia with synostoses. It is reached by an entirely different mechanism — regulatory reallocation at the HOXD locus, with intact coding sequence — whereas this syndrome is a straightforward contiguous-gene deletion. Copy-number analysis distinguishes them by locus.

Langer mesomelic dysplasia

Overlapping Features Biallelic SHOX deficiency; more severe limb shortening and no acral synostoses or additional congenital malformations.

{ }

Source YAML

click to show

name: Mesomelia-Synostoses Syndrome
synonyms:
- mesomelic dysplasia with acral synostoses, Verloes-David-Pfeiffer type
- Verloes-David-Pfeiffer syndrome
- MSS
creation_date: "2026-08-27T00:00:00Z"
category: Mendelian
description: >-
  Mesomelia-synostoses syndrome is a rare autosomal dominant disorder combining
  mesomelic limb shortening with acral synostoses and multiple congenital
  malformations. It is a contiguous-gene microdeletion syndrome: every reported
  patient carries an interstitial 8q13 deletion of 582 to 738 kb that removes
  exactly two genes, SULF1 and SLCO5A1. SULF1 encodes heparan sulfate
  6-O-endosulfatase 1, which edits the sulfation pattern of heparan sulfate and
  so tunes the availability of the growth factors that pattern the developing
  skeleton; it is most highly transcribed in human osteoblasts and cartilage,
  which is why it is the better candidate of the two. SLCO5A1 is an orphan
  organic anion transporter expressed in brain and heart with no known function.
  Because the two genes are always co-deleted, the contribution of each has not
  been separated.
disease_term:
  preferred_term: mesomelia-synostoses syndrome
  term:
    id: MONDO:0010881
    label: mesomelia-synostoses syndrome
parents:
- Skeletal Dysplasia
- Mesomelic Dysplasia
- Contiguous gene deletion syndrome
notes: >-
  Attribution. The ISDS row names both SULF1 and SLCO5A1, and this entry keeps
  both rather than collapsing to SULF1. The defining study's own conclusion is
  carefully hedged — SULF1 haploinsufficiency "contributes", and the authors
  suggest that SULF1 plus SLCO5A1 haploinsufficiency, or a position effect on a
  neighbouring gene, "could be necessary". No patient with a single-gene lesion
  in either gene has been reported, so the two-gene requirement is untested
  rather than established, and the mechanism section says so.
classifications:
  harrisons_chapter:
  - classification_value: GENETICS_ENVIRONMENT_DISEASE
    notes: >-
      A Mendelian contiguous-gene deletion syndrome; tagged on the genetics
      axis.
  isds_skeletal_category:
  - classification_value: mesomelic_and_rhizomesomelic_dysplasias
    notes: >-
      ISDS Nosology of Genetic Skeletal Disorders, 2023 revision (Unger et al.,
      PMID:36779427), group 15 "Mesomelic and rhizo-mesomelic dysplasias", row
      NOS 15-0140, listed as "Mesomelic dysplasia with acral synostoses
      (Verloes-David-Pfeiffer type)" (MIM 600383, AD) with genes SULF1 and
      SLCO5A1, and the row's own comment describing it as a microdeletion
      syndrome involving two adjacent genes. The 2019 revision (Mortier et al.,
      PMID:31633310) numbered the same group 17.
prevalence:
- population: Worldwide
  measure_type: CASES_IN_LITERATURE
  prevalence_class: ULTRA_RARE
  notes: >-
    Five patients in four unrelated families at the time the molecular cause was
    identified. No denominator-based estimate exists.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      So far, five patients in four unrelated families have been reported
      worldwide with MMS.
    explanation: >-
      Gives the cumulative case count, the basis for the ULTRA_RARE band.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Autosomal dominant, from heterozygous deletion of the 8q13 interval. The
    deletions are non-recurrent — breakpoint sequencing in two families showed
    they do not arise from low-copy-repeat-mediated recombination — so each is a
    distinct event rather than a common rearrangement hotspot product.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral
      synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant
      disorder characterized by mesomelic limb shortening, acral synostoses, and
      multiple congenital malformations.
    explanation: >-
      States the inheritance mode together with the defining features.
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Breakpoint sequence analyses performed in two families showed nonrecurrent
      deletions.
    explanation: >-
      Supports the non-recurrent nature of the deletions.
pathophysiology:
- name: 8q13 Contiguous Deletion of SULF1 and SLCO5A1
  biological_scale: MOLECULAR
  genes:
  - preferred_term: SULF1
    term:
      id: hgnc:20391
      label: SULF1
  - preferred_term: SLCO5A1
    term:
      id: hgnc:19046
      label: SLCO5A1
  genetic_context:
    genes:
    - preferred_term: SULF1
      term:
        id: hgnc:20391
        label: SULF1
    - preferred_term: SLCO5A1
      term:
        id: hgnc:19046
        label: SLCO5A1
    allele_type: interstitial 8q13 deletion of 582-738 kb
    zygosity: HETEROZYGOUS
    functional_impact_category: LOSS_OF_FUNCTION
  description: >-
    Array CGH found an interstitial 8q13 deletion in every patient. The
    deletions differ in size but converge on the same two-gene content, which is
    what identified the interval. Because no patient has been reported with a
    lesion in only one of the two genes, the deletion is curated here as the
    unit of causation, with the relative contributions of the two genes left
    open.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass
      only two genes: SULF1, encoding the heparan sulfate 6-O-endosulfatase 1,
      and SLCO5A1, encoding the solute carrier organic anion transporter family
      member 5A1.
    explanation: >-
      Establishes the deletion interval and its exact two-gene content.
  downstream:
  - target: Loss of Heparan Sulfate 6-O-Endosulfatase Activity
    causal_link_type: DIRECT
    description: >-
      SULF1 haploinsufficiency follows directly from the deletion.
- name: Loss of Heparan Sulfate 6-O-Endosulfatase Activity
  biological_scale: MOLECULAR
  description: >-
    SULF1 removes 6-O-sulfate groups from heparan sulfate proteoglycans at the
    cell surface, and that sulfation pattern determines how tightly heparan
    sulfate binds and sequesters the growth factors — Wnt, FGF, BMP, hedgehog —
    that pattern the skeleton. Losing an endosulfatase therefore changes growth
    factor availability rather than any structural protein. The expression data
    point the same way: SULF1 transcripts are highest in human osteoblasts and
    cartilage, while its co-deleted neighbour is a brain- and heart-expressed
    transporter of unknown function.
  molecular_functions:
  - preferred_term: heparan sulfate 6-O-endosulfatase activity
    modifier: DECREASED
    term:
      id: GO:0008201
      label: heparin binding
  biological_processes:
  - preferred_term: glycosaminoglycan metabolic process
    modifier: DECREASED
    term:
      id: GO:0030203
      label: glycosaminoglycan metabolic process
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      SULF1 acts as a regulator of numerous growth factors in skeletal embryonic
      development whereas the function of SLCO5A1 is yet unknown.
    explanation: >-
      Establishes SULF1's role as a growth-factor regulator in skeletal
      development and the absence of any known SLCO5A1 function.
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Real-time quantitative RT-PCR analysis showed the highest levels of SULF1
      transcripts in human osteoblasts and cartilage whereas SLCO5A1 was highly
      expressed in human fetal and adult brain and heart.
    explanation: >-
      The tissue-expression argument that makes SULF1 the better candidate of
      the two co-deleted genes.
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our results strongly suggest that haploinsufficiency of SULF1 contributes
      to this mesomelic chondrodysplasia, highlighting the critical role of
      endosulfatase in human skeletal development.
    explanation: >-
      The authors' own conclusion, stated as "strongly suggest" and
      "contributes" rather than as sufficiency — which is why this node does not
      claim SULF1 loss alone explains the disorder.
  downstream:
  - target: Mesomelic Shortening with Acral Synostoses
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Which growth-factor pathway mediates the skeletal phenotype has not been
      identified.
- name: Mesomelic Shortening with Acral Synostoses
  biological_scale: ORGANISM
  description: >-
    The clinical endpoint: mesomelic limb shortening together with acral
    synostoses and additional congenital malformations. The pairing of mesomelia
    with synostosis is the recognizable signature, and it is shared with the
    HOXD-related Kantaputra type, which reaches the same combination by a
    completely different route.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a rare autosomal-dominant disorder characterized by mesomelic limb
      shortening, acral synostoses, and multiple congenital malformations
    explanation: >-
      Gives the defining clinical triad this node represents.
  downstream:
  - target: Mesomelic Limb Shortening
    causal_link_type: DIRECT
    description: >-
      Loss of endosulfatase editing changes growth-factor availability in the
      developing zeugopod.
  - target: Acral Synostoses
    causal_link_type: DIRECT
    description: >-
      Heparan sulfate sulfation state governs the growth-factor gradients that
      separate adjacent skeletal elements, so losing that control is a plausible
      route to failed segmentation. Which growth factor mediates it is not
      established.
phenotypes:
- category: Skeletal
  name: Mesomelic Limb Shortening
  phenotype_term:
    preferred_term: Mesomelia
    term:
      id: HP:0003027
      label: Mesomelia
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a rare autosomal-dominant disorder characterized by mesomelic limb
      shortening, acral synostoses, and multiple congenital malformations
    explanation: >-
      Mesomelic limb shortening is the first of the defining features.
- category: Skeletal
  name: Acral Synostoses
  description: >-
    Fusions in the distal limb, the feature that pairs with mesomelia to give
    the syndrome its name.
  phenotype_term:
    preferred_term: Synostosis of carpal bones
    term:
      id: HP:0005048
      label: Synostosis of carpal bones
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a rare autosomal-dominant disorder characterized by mesomelic limb
      shortening, acral synostoses, and multiple congenital malformations
    explanation: >-
      Establishes acral synostoses as a defining feature. The abstract does not
      say which bones fuse, so the HP binding to carpal synostosis is the
      closest available term rather than a stated finding, and the evidence is
      PARTIAL.
genetic:
- name: SULF1
  gene_term:
    preferred_term: SULF1
    term:
      id: hgnc:20391
      label: SULF1
  relationship_type: CAUSATIVE
  notes: >-
    Heparan sulfate 6-O-endosulfatase 1, at 8q13. Deleted in every reported
    patient and the better candidate of the two co-deleted genes on both
    functional and expression grounds. No patient with an isolated SULF1 lesion
    has been reported, so its sufficiency is untested.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our results strongly suggest that haploinsufficiency of SULF1 contributes
      to this mesomelic chondrodysplasia, highlighting the critical role of
      endosulfatase in human skeletal development.
    explanation: >-
      The authors' attribution of the skeletal phenotype primarily to SULF1
      haploinsufficiency.
- name: SLCO5A1
  gene_term:
    preferred_term: SLCO5A1
    term:
      id: hgnc:19046
      label: SLCO5A1
  relationship_type: COOPERATING
  notes: >-
    Solute carrier organic anion transporter family member 5A1, immediately
    adjacent to SULF1 and co-deleted in every patient. Its function is unknown
    and its expression is brain- and heart-predominant rather than skeletal, so
    it is recorded as a cooperating rather than a primary locus — the defining
    study proposes that combined SULF1 and SLCO5A1 haploinsufficiency, or a
    position effect on a neighbouring gene, may be what is required.
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      we suggest that haploinsufficiency of SULF1 combined with
      haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring
      gene through position effect) could be necessary in the pathogenesis of
      MSS
    explanation: >-
      The proposal that SLCO5A1 co-haploinsufficiency may be required, stated as
      a suggestion and with an explicit alternative, which is why this is
      COOPERATING and PARTIAL.
diagnosis:
- name: Copy-Number Analysis of 8q13
  description: >-
    Confirmed by demonstrating an interstitial 8q13 deletion encompassing SULF1
    and SLCO5A1. Array CGH is the assay that identified the interval and remains
    the appropriate first-line test; the deletions are non-recurrent, so there
    is no single breakpoint-specific assay to use instead.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: NCIT:C15709
      label: Genetic Testing
  evidence:
  - reference: PMID:20602915
    reference_title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      By using whole-genome oligonucleotide array CGH, we have identified an
      interstitial deletion at 8q13 in all patients.
    explanation: >-
      Names the assay and its yield in the defining series.
differential_diagnoses:
- name: Mesomelic dysplasia, Kantaputra type
  description: >-
    The other group-15 disorder that pairs mesomelia with synostoses. It is
    reached by an entirely different mechanism — regulatory reallocation at the
    HOXD locus, with intact coding sequence — whereas this syndrome is a
    straightforward contiguous-gene deletion. Copy-number analysis distinguishes
    them by locus.
- name: Langer mesomelic dysplasia
  description: >-
    Biallelic SHOX deficiency; more severe limb shortening and no acral
    synostoses or additional congenital malformations.
discussions:
- discussion_id: mss_two_gene_requirement
  kind: KNOWLEDGE_GAP
  prompt: >-
    Is SULF1 haploinsufficiency alone sufficient to cause mesomelia-synostoses
    syndrome, or is co-deletion of SLCO5A1 (or a position effect) genuinely
    required?
  attaches_to:
  - pathophysiology#8q13 Contiguous Deletion of SULF1 and SLCO5A1
  rationale: >-
    Every reported patient has both genes deleted, so the two-gene hypothesis
    has never been tested against the one-gene alternative in humans. The
    question decides whether an isolated SULF1 loss-of-function variant found
    incidentally should be reported as causal for this syndrome — a question a
    diagnostic laboratory will eventually face — and it is answerable either by
    a patient with a smaller deletion or by a single-gene mouse model.
references:
- reference: PMID:20602915
  title: "Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13."
- reference: PMID:36779427
  title: "Nosology of genetic skeletal disorders: 2023 revision."

📚

References & Deep Research

References

2

PMID:20602915

Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13.

No top-level findings curated for this source.

PMID:36779427

Nosology of genetic skeletal disorders: 2023 revision.

No top-level findings curated for this source.

Mesomelia-Synostoses Syndrome

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Genetic Associations

Diagnosis

Prevalence

Differential Diagnoses

Source YAML

References & Deep Research

References