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Koolen-de Vries syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Global developmental delay; and very common findings: Generalized hypotonia, Conspicuously happy disposition, Pear-shaped nose, and Bulbous nose. 79 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	8	Poor speech, Seizure, Intellectual disability
Head and neck	7	Cleft palate, Microcephaly, Cleft upper lip
Arms and legs	4	Positional foot deformity, Prominent fingertip pads, Hypotrophy of the small hand muscles
Heart and blood vessels	4	Bicuspid aortic valve, Aortic root aneurysm, Ventricular septal defect
Bones and joints	4	Joint hypermobility, Vertebral fusion, Sideways curvature of the spine (scoliosis)
Eyes	3	Strabismus, Cataract, Ptosis
Growth and development	3	Short stature, Failure to thrive, Intrauterine growth retardation
Muscles	2	Generalized hypotonia, Hypotrophy of the small hand muscles
Skin	2	Dry skin, Eczematoid dermatitis
Kidneys and urinary system	1	Recurrent urinary tract infections
Blood and immune system	1	Recurrent urinary tract infections
Digestive system	1	Feeding difficulties in infancy
Nervous system (morphological)	1	Morphological central nervous system abnormality

Age of onset: at birth, childhood.

GeneReviews

Clinical Guidance

Koolen-de Vries syndrome (KdVS) has a clinically recognizable phenotype that includes neonatal/childhood hypotonia, developmental delay/ intellectual givdisability, dysmorphisms , speech and language delays, congenital malformations, and behavioral features. To date, more than 200 individuals have been identified with KdVS [, , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Koolen-de Vries Syndrome: Frequency of Select Features

Feature	Frequency
Very common1	Common2
See Dysmorphic craniofacial features after this table. Developmental delay/ intellectual disability	Particularly in areas of speech language delay Hypotonia

Source: GeneReviews — "Koolen-de Vries Syndrome"

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

No consensus clinical diagnostic criteria for Koolen-de Vries syndrome (KdVS) have been published.

Suggestive Findings

KdVS should be considered in probands with the following clinical and family history findings.

Clinical findings

Mild-to-moderate developmental delay or intellectual disability in which speech and language development is particularly affected

AND

Neonatal/childhood hypotonia and feeding difficulties
Epilepsy
Dysmorphic facial features (See and .)
Hypermetropia
Congenital heart anomalies
Congenital renal/urologic anomalies
Hypermobility of the joints and/or joint dislocation/dysplasia
Deformities of the spine and/or feet

Family history. Because KdVS is typically caused by a de novo pathogenic variant, most probands represent a simplex case (i.e., a single occurrence in a family).

Source: GeneReviews — "Koolen-de Vries Syndrome"

GeneReviews

Differential Diagnosis

The most common findings in Koolen-de Vries syndrome (KdVS) – developmental delay and childhood hypotonia – are common and relatively nonspecific indications for molecular cytogenetic analysis. However, the concurrent finding of characteristic facial dysmorphic features, epilepsy, hypermetropia, congenital heart defects, renal or urologic anomalies, cryptorchidism, and/or distinctive friendly/amiable behavior may prompt specific consideration of the diagnosis of KdVS. See for other diagnoses that may be considered in individuals with developmental delay, childhood hypotonia, and additional findings overlapping those observed in KdVS.

Table 3.

Selected Disorders with Developmental Delay, Childhood Hypotonia, and Concurrent Findings Similar to Koolen-de Vries Syndrome

Source: GeneReviews — "Koolen-de Vries Syndrome"

Genetic testing for KANSL1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for Koolen-de Vries syndrome has been reported in the published literature.

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 Koolen-de Vries syndrome. The disease remains an area of unmet medical need.

Gene therapy approaches for Koolen-de Vries syndrome have been reported in the published literature.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the clinical consequences in an individual diagnosed with Koolen-de Vries syndrome (KdVS), the evaluations (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis of Koolen-de Vries Syndrome

System/Concern	Evaluation	Comment
Constitutional	Assessment of growth parameters to identify those w/failure to thrive	Consider investigation of growth hormone deficiency in persons w/short stature. Gastrointestinal/
Feeding	Feeding assessment	Assess for sucking swallowing difficulties need for feeding therapy in infancy.
Development	Developmental assessment	To incl motor, adaptive, cognitive, speech/language eval; Eval for early intervention/ special education
Neurologic	Brain imaging studies in persons w/microcephaly /or seizure	Consideration of Chiari malformation type 1 in those w/suggestive symptoms (headache, neck pain, cerebellar signs, or muscle weakness)1 EEG if seizures are suspected
Psychiatric

Source: GeneReviews — "Koolen-de Vries Syndrome"

Clinical Trials

1 trial found

Explore Trials

Prognosis

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

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations in are recommended. Table 6. Recommended Surveillance for Individuals with Koolen-de Vries Syndrome

System/Concern	Evaluation	Frequency
Integument	Full skin exam in those w/lighter skin tones or skin types who are at greater risk for developing melanoma	Annually
Ophthalmologic involvement	Ophthalmologic eval	Per treating ophthalmologist Low vision services
Hearing	Audiologic eval	Annually, or as clinically indicated ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "Koolen-de Vries Syndrome"

Phenotype severity distribution: 1 always present feature, 4 very common features, 32 common features.

Estimated prevalence: Unknown (Unknown prevalence).

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.

1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.

16 publications have been identified in PubMed for Koolen-de Vries syndrome. Research spans Case Report / Case Series (31%), Review / Meta-Analysis (19%), and Diagnostic / Biomarker (13%).

Research Type	Count	% of Total
Patient case studies	5	31%
Research summaries	3	19%
Testing and diagnosis research	2	13%
Laboratory research	2	13%
Other research	1	6%
Clinical study results	1	6%
Disease patterns and progression	1	6%
New treatment approaches	1	6%

Recent Publications

Sridharan S (2026). [PMID: 42151137](https://pubmed.ncbi.nlm.nih.gov/42151137/). *Nat Commun*. [Basic Science / Preclinical]
Verboven AHA (2026). [PMID: 41680331](https://pubmed.ncbi.nlm.nih.gov/41680331/). *Mol Psychiatry*. [Gene Therapy / Novel Therapeutics]
Soliman A (2026). [PMID: 41631283](https://pubmed.ncbi.nlm.nih.gov/41631283/). *J Med Cases*. [Case Report / Case Series]
Bakhos C (2026). [PMID: 41767010](https://pubmed.ncbi.nlm.nih.gov/41767010/). *Front Neurol*. [Other]
Huang H (2025). [PMID: 41457108](https://pubmed.ncbi.nlm.nih.gov/41457108/). *Mol Genet Genomics*. [Diagnostic / Biomarker]
L'Erario FF (2025). [PMID: 40735694](https://pubmed.ncbi.nlm.nih.gov/40735694/). *Genes Dis*. [Diagnostic / Biomarker]
König L (2025). [PMID: 40254345](https://pubmed.ncbi.nlm.nih.gov/40254345/). *Curr Top Dev Biol*. [Review / Meta-Analysis]
Sridharan S (2025). [PMID: 41040191](https://pubmed.ncbi.nlm.nih.gov/41040191/). *bioRxiv*. [Basic Science / Preclinical]
Groulx-Boivin É (2025). [PMID: 40392080](https://pubmed.ncbi.nlm.nih.gov/40392080/). *Epileptic Disord*. [Case Report / Case Series]
Sayik D (2025). [PMID: 40561847](https://pubmed.ncbi.nlm.nih.gov/40561847/). *Epilepsy Behav*. [Clinical Trial Publication]

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Koolen-de Vries syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Koolen-de Vries syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Penetrance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Patient Support

Patient Advocacy Groups

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team