Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome: Research & Drug Discovery Data

Drug discovery

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On emerging therapies

Overview

Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome (Nishimura type) is an ultra-rare genetic disorder characterized by skeletal abnormalities (spondyloepiphyseal dysplasia, platyspondyly), premature skull suture fusion, ocular cataracts, cleft palate, and developmental delays. Clinical manifestations are typically evident at birth or early childhood, with progressive skeletal changes and visual impairment. Associated features include distinctive facial dysmorphism, micrognathia, and thoracic kyphosis [1][5][15].

Population

Reported in only four Japanese siblings from nonconsanguineous parents [1][5].
Presumed autosomal recessive inheritance pattern [7][12].

Burden

Physical: Severe mobility restrictions, chronic pain, and vision loss [5][15].
Developmental: Global delays requiring lifelong adaptive support [1][12].
Care complexity: Requires coordination across 7+ medical specialties [2][5].

Therapies

Multidisciplinary care: Surgical correction of craniosynostosis and cleft palate, cataract removal, and orthopedic management of skeletal anomalies [2][9].
Supportive interventions: Physical/occupational therapy for mobility limitations and intellectual disability support [2][5].
Surveillance: Regular monitoring for complications (retinal detachment, spinal deformities) [2][5].

Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases, rare otorhinolaryngological diseases, rare surgical maxillo-facial diseases

Research Papers

1 drug discovery papers about Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome. Recent publications:

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Small molecules

small molecules

2023-01-18 | Reduced glycolysis links resting zone chondrocyte proliferation in the growth plate

A gain-of-function mutation of the chondrocyte-specific microRNA, miR-140-5p, encoded by the MIR140 gene, causes spondyloepiphyseal dysplasia, Nishimura type (SEDN, also known as SED, MIR140 type; MIM, 611894). We reported that a mouse model for SEDN showed a unique growth plate phenotype that is characterized by an expansion of the resting zone of the growth plate and an increase in resting chondrocytes, of which the mechanism of regulation is poorly understood. We found that the miR-140 mutant chondrocytes showed a significant reduction of Hif1a, the master transcription factor that regulates energy metabolism in response to hypoxia. Based on this finding, we hypothesized that energy metabolism plays a regulatory role in resting chondrocyte proliferation and growth plate development. In this study, we show that suppression of glycolysis via LDH ablation causes an expansion of the resting zone and skeletal developmental defects. We have also found that reduced glycolysis results in reduced histone acetylation in the miR-140 mutant as well as LDH-deficient chondrocytes likely due to the reduction in acetyl-CoA generated from mitochondria-derived citrate. Reduction in acetyl-CoA conversion from citrate by deleting Acly caused an expansion of the resting zone and a similar gross phenotype to LDH-deficient bones without inducing energy deficiency, suggesting that the reduced acetyl-CoA, but not the ATP synthesis deficit, is responsible for the increase in resting zone chondrocytes. Comparison of the transcriptome between LDH-deficient and Acly-deficient chondrocytes also showed overlapping changes including upregulation in Fgfr3. We also confirmed that overexpression of an activation mutation of Ffgr3 causes an expansion of resting zone chondrocytes. These data demonstrate the association between reduced glycolysis and an expansion of the resting zone and suggest that it is caused by acetyl-CoA deficiency, but not energy deficiency, possibly through epigenetic upregulation of FGFR3 signaling.

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small molecules

2023-01-18 | Reduced glycolysis links resting zone chondrocyte proliferation in the growth plate

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Drug Discovery Landscape

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Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome

Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome

Spondyloepiphyseal dysplasia-craniosynostosis-cleft palate-cataracts-intellectual disability syndrome

Overview

Population

Burden

Therapies

Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases, rare otorhinolaryngological diseases, rare surgical maxillo-facial diseases

Research Papers

small molecules

2023-01-18 | Reduced glycolysis links resting zone chondrocyte proliferation in the growth plate

small molecules

2023-01-18 | Reduced glycolysis links resting zone chondrocyte proliferation in the growth plate

Drug Discovery Landscape

Updated: Nov 10, 2026