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Microphthalmia with brain and digit anomalies is characterized by anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development.
Features include always present findings: Global developmental delay; and sometimes findings: Short middle phalanx of finger. 60 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Arms and legs | 5 | Toe syndactyly, Short middle phalanx of finger, Finger syndactyly |
Head and neck | 5 | Lambdoidal craniosynostosis, Microcephaly, Cleft palate |
Muscles | 4 | Severe muscular hypotonia, Low muscle tone (hypotonia), Cerebral cortical atrophy |
Eyes | 4 | Nystagmus, Retinal dystrophy, Aplasia of the optic tract |
Hormones | 4 | Adrenal hypoplasia, Female hypogonadism, Hypothyroidism |
Brain and nerves | 4 | Absent speech, Global developmental delay, Cerebral cortical atrophy |
Ears | 1 | Hearing loss (hearing impairment) |
Kidneys and urinary system | 1 | Renal hypoplasia |
Growth and development | 1 | Failure to thrive |
Nervous system (morphological) | 1 | Morphological central nervous system abnormality |
BMP4 encodes bone morphogenetic protein 4 (408 aa). Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis. Highest expression in Vagina (25.9 TPM) and Bladder (23.4 TPM).
Microphthalmia with brain and digit anomalies is associated with mutations in the BMP4 gene on chromosome 14.
BMP4 is classified as a druggable target (Druggable Genome, Growth Factor, and Transcription Factor categories) with score 0.0.
Genetic testing for BMP4 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 1 always present feature.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for microphthalmia with brain and digit anomalies.
7 publications have been identified in PubMed for microphthalmia with brain and digit anomalies. Research spans Case Report / Case Series (43%), Basic Science / Preclinical (29%), and Review / Meta-Analysis (14%).
Chesneau B (2026). [PMID: 41568967](https://pubmed.ncbi.nlm.nih.gov/41568967/). *Clin Genet*. [Epidemiology / Natural History]
Yang Y (2026). [PMID: 41708596](https://pubmed.ncbi.nlm.nih.gov/41708596/). *Cell Death Dis*. [Basic Science / Preclinical]
Li C (2025). [PMID: 40736845](https://pubmed.ncbi.nlm.nih.gov/40736845/). *Adv Exp Med Biol*. [Review / Meta-Analysis]
Murgiano L (2024). [PMID: 38682429](https://pubmed.ncbi.nlm.nih.gov/38682429/). *G3 (Bethesda)*. [Case Report / Case Series]
Sauvestre C (2024). [PMID: 39390895](https://pubmed.ncbi.nlm.nih.gov/39390895/). *Cardiol Young*. [Case Report / Case Series]
Elsayed MEA (2024). [PMID: 39027323](https://pubmed.ncbi.nlm.nih.gov/39027323/). *Am J Ophthalmol Case Rep*. [Case Report / Case Series]
Ceroni F (2024). [PMID: 39455595](https://pubmed.ncbi.nlm.nih.gov/39455595/). *Nat Commun*. [Basic Science / Preclinical]
Data assembled from 6 of 12 sources · Last updated Sep 18, 2026, 3:24 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center