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Split hand - split foot - deafness is an extremely rare genetic syndrome reported in a few families to date and characterized clinically by split hand/split foot malformation (SHFM) and mild to moderate sensorineural hearing loss, sometimes associated with cleft palate and intellectual deficit.
Features include always present findings: Inner ear hearing loss (sensorineural hearing impairment), Split foot, and Split hand; and common findings: Severe short stature, Sideways curvature of the spine (scoliosis), Tapered finger, and Frontal bossing.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Arms and legs | 3 | Split foot, Split hand, Tapered finger |
Growth and development | 1 | Severe short stature |
Bones and joints | 1 | Sideways curvature of the spine (scoliosis) |
Ears | 1 | Inner ear hearing loss (sensorineural hearing impairment) |
DLX5 encodes distal-less homeobox 5 (289 aa). Transcriptional factor involved in bone development. Acts as an immediate early BMP-responsive transcriptional activator essential for osteoblast differentiation. Highest expression in Skin Sun Exposed Lower leg (34.7 TPM) and Skin Not Sun Exposed Suprapubic (30.0 TPM).
Split hand-foot malformation 1 with sensorineural hearing loss is associated with mutations in the DLX5 gene on chromosome 7.
The DLX5 protein participates in Expression of DLX5 in the neural plate border, RUNX2 gene expression from distal (P1) promoter is inhibited by NKX3-2, MSX2 and RUNX2-P1, and stimulated by DLX5,(DLX6), and Embryonic ectoderm cell produces mammary stem cell pathways.
DLX5 is classified as a druggable target (Transcription Factor category) with score 8.7.
Genetic testing for DLX5 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 3 always present features, 4 common features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for split hand-foot malformation 1 with sensorineural hearing loss.
1 publication has been identified in PubMed for split hand-foot malformation 1 with sensorineural hearing loss. Research spans Case Report / Case Series (100%).
Taşdelen E (2025). [PMID: 41064052](https://pubmed.ncbi.nlm.nih.gov/41064052/). *Mol Syndromol*. [Case Report / Case Series]
Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 2:54 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center