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White matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome is a very rare neurological condition. The few patients described in the medical literature were characterized by brain anomalies; an unusual face with broad nasal root, wide spaced eyes (hypertelorism) and a very small chin (micrognathia); failure to thrive; severe intellectual disability ;and lack of muscle tone (hypotonia). Exams of the brain showed a poor development (hypoplasia) of the pale part of the brain known as white matter, and an absent or abnormal corpus callosum (nerve fibers joining the two hemispheres of the brain). Only a few cases have being described. The cause is unknown but may be related to a disorder of axonal development. The described cases seem to be inherited in an autosomal recessive or X-linked way. Corpus callosum agenesis is one of the more frequent congenital malformations. It can be either asymptomatic or associated with intellectual disability, epilepsy, or psychiatric syndromes. It can be part of several genetic syndromes, such as Aicardi syndrome, Andermann syndrome and Apert syndrome, trisomies 13, 18 ; or result from metabolic causes; drugs (cocaine); or viral infection (influenza). Many patients with corpus callosum anomalies have other brain anomalies, including white matter hypoplasia. There is no information on specific treatment for this condition.
Features include very common findings: Microcephaly, Hypertelorism, Micrognathia, and Wide nasal bridge and others; and common findings: Downslanted palpebral fissures, Synophrys, Enlarged brain ventricles (ventriculomegaly), and Aplasia/Hypoplasia of the cerebellum. 17 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 5 | Intellectual disability, Overactive reflexes (hyperreflexia), Enlarged brain ventricles (ventriculomegaly) |
Biomarker and diagnostic research for white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome has been reported in the published literature.
Phenotype severity distribution: 12 very common features, 4 common features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome.
118 publications have been identified in PubMed for white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome. Research spans Review / Meta-Analysis (69%), Basic Science / Preclinical (14%), and Epidemiology / Natural History (6%).
Research Type | Count | % of Total |
|---|---|---|
Research summaries | 82 | 69% |
Data assembled from 4 of 12 sources · Last updated Sep 20, 2026, 6:40 AM UTC
European rare disease database
Genetic and Rare Diseases Info Center
Muscles | 2 | Low muscle tone (hypotonia), Cerebral cortical atrophy |
Head and neck | 1 | Microcephaly |
Growth and development | 1 | Short stature |
Laboratory research |
16 |
14% |
Disease patterns and progression | 7 | 6% |
Patient case studies | 5 | 4% |
Testing and diagnosis research | 3 | 3% |
Other research | 2 | 2% |
New treatment approaches | 2 | 2% |
Clinical study results | 1 | 1% |
Anderson EN (2026). [PMID: 41468891](https://pubmed.ncbi.nlm.nih.gov/41468891/). *Am J Hum Genet*. [Basic Science / Preclinical]
Papazachariou A (2026). [PMID: 41128447](https://pubmed.ncbi.nlm.nih.gov/41128447/). *Curr Opin Clin Nutr Metab Care*. [Review / Meta-Analysis]
Serpieri V (2026). [PMID: 41720098](https://pubmed.ncbi.nlm.nih.gov/41720098/). *Am J Hum Genet*. [Gene Therapy / Novel Therapeutics]
Buel KL (2026). [PMID: 41569909](https://pubmed.ncbi.nlm.nih.gov/41569909/). *FP Essent*. [Review / Meta-Analysis]
Amado C (2026). [PMID: 40975490](https://pubmed.ncbi.nlm.nih.gov/40975490/). *Ann Allergy Asthma Immunol*. [Review / Meta-Analysis]
Shabshin G (2025). [PMID: 40261331](https://pubmed.ncbi.nlm.nih.gov/40261331/). *Orthopadie (Heidelb)*. [Review / Meta-Analysis]
Patel R (2025). [PMID: 40204117](https://pubmed.ncbi.nlm.nih.gov/40204117/). *J Neuroradiol*. [Basic Science / Preclinical]
Brokke KE (2025). [PMID: 40634186](https://pubmed.ncbi.nlm.nih.gov/40634186/). *Br J Anaesth*. [Review / Meta-Analysis]
Krusche M (2025). [PMID: 40960635](https://pubmed.ncbi.nlm.nih.gov/40960635/). *Z Rheumatol*. [Review / Meta-Analysis]
Gencer NS (2025). [PMID: 41291504](https://pubmed.ncbi.nlm.nih.gov/41291504/). *BMC Geriatr*. [Epidemiology / Natural History]