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central nervous system malformation - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

central nervous system malformation

MONDO:0020022

Overview

OnsetJUVENILE, CHILDHOOD, CONGENITAL, ANTENATAL, INFANTILE

ResearchLimited published research (5 articles)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: adolescence, childhood, at birth, before birth, infancy.

GeneReviews

Clinical Guidance

CASK disorders are more commonly reported in females and include a spectrum of phenotypes that differs in females and males:

Source: GeneReviews — "CASK Disorders"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

CASK disorders are associated with a wide phenotypic spectrum ranging from mild-to-severe intellectual disability with or without nystagmus to moderate-to-profound intellectual disability and progressive microcephaly with pontine and cerebellar hypoplasia (MICPCH), often associated with seizures. CASK disorders are X-linked and more commonly reported in females than in males. MICPCH in females is the most common phenotype to date.

Suggestive Findings

CASK disorders should be considered in individuals with intellectual disability of any degree and any of the following additional findings:

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for central nervous system malformation. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a CASK disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with CASK Disorders

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with CASK Disorders

System/Concern

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for central nervous system malformation.

5 publications have been identified in PubMed for central nervous system malformation. Research spans Case Report / Case Series (60%), Clinical Trial Publication (20%), and Epidemiology / Natural History (20%).

Recent Publications

Bhardwaj S (2025). [PMID: 41189858](https://pubmed.ncbi.nlm.nih.gov/41189858/). *Cureus*. [Case Report / Case Series]
Grassi AG (2025). [PMID: 40713925](https://pubmed.ncbi.nlm.nih.gov/40713925/). *American journal of medical genetics. Part A*. [Case Report / Case Series]
Efimova I (2025). [PMID: 41096571](https://pubmed.ncbi.nlm.nih.gov/41096571/). *International journal of molecular sciences*. [Case Report / Case Series]
Westenius E (2024). [PMID: 38268232](https://pubmed.ncbi.nlm.nih.gov/38268232/). *Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology*. [Clinical Trial Publication]
Kyonen M (2024). [PMID: 38457309](https://pubmed.ncbi.nlm.nih.gov/38457309/). *Archivos argentinos de pediatria*. [Epidemiology / Natural History]

Data assembled from 4 of 12 sources · Last updated Sep 19, 2026, 6:43 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:98044

GARD

Genetic and Rare Diseases Info Center

GARD:19394

Questions for Your Care Team

→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Intellectual Disability and Microcephaly with Pontine and Cerebellar Hypoplasia (MICPCH) Table 2. Genes of Interest in the Differential Diagnosis of MICPCH

Gene(s)	Disorder	MOI	Clinical Features	Brain MRI Findings
TSEN54	PCH2	AR	Generalized clonus ("jitteriness") w/lack of voluntary motor development later development of chorea spasticity, impaired swallowing, (in some) epilepsy; Persons w/PCH2 usually live into childhood.	In persons w/PCH2/PCH4:; Cerebellar hemispheres are more affected than the vermis, "dragonfly" appearance in coronal images.2; Pontine hypoplasia is more severe than in females w/MICPCH.; Corpus callosum is often thin hypoplastic.
TSEN54	PCH4	AR	Polyhydramnios, contractures, severe generalized clonus, central respiratory failure usually neonatal death	—
ARXSTXBP1(80 genes)1	Ohtahara syndrome	XLAD	Early-infantile epileptic encephalopathy w/suppression burst	May or may not be assoc w/abnormalities on brain MRI AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; PCH = pontocerebellar hypoplasia; XL = X-linked 1. See Phenotypic Series: Early Infantile Epileptic Encephalopathy for genes associated with this phenotype in OMIM. 2.

Source: GeneReviews — "CASK Disorders"

Kisho

central nervous system malformation

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials

central nervous system malformation

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Therapies Under Investigation

Clinical Trials