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spondyloepimetaphyseal dysplasia with joint laxity - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

spondyloepimetaphyseal dysplasia with joint laxity

MONDO:0019675

Also known as:SEMD-JLSEMDJLSEMDJL1

Overview

A form of skeletal dysplasia characterized by severe dwarfism, generalized articular hypermobility, and progressive spinal malalignment.

OnsetCHILDHOOD, CONGENITAL

ResearchLimited published research (8 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: childhood, at birth.

GeneReviews

Clinical Guidance

EXOC6B-related spondyloepimetaphyseal dysplasia with joint laxity (EXOC6B-SEMD-JL) is characterized by multiple joint dislocations, joint laxity, short stature, scoliosis, kyphosis, and skeletal dysplasia (delayed carpal/tarsal bone ossification, leptodactyly, slender ribs, and vertebral anomalies). To date, seven individuals from five unrelated families have been identified with biallelic pathogenic variants in EXOC6B [; ; ; Authors, personal communication]. Most individuals have normal intellect, though developmental delay and hydrocephalus were noted in one individual . The following description of the phenotypic features associated with this condition is based on these reports. Table 2. EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity: Frequency of Select Features

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

Suggestive Findings

EXOC6B-related spondyloepimetaphyseal dysplasia with joint laxity (EXOC6B-SEMD-JL) should be suspected in probands with the following clinical, imaging, and family history findings.

Clinical findings

Congenital dislocations of the hips and knees; may also affect elbows, wrists, and/or ankles
Joint laxity affecting all joints and most evident at the wrists and fingers

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 spondyloepimetaphyseal dysplasia with joint laxity. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines for EXOC6B-related spondyloepimetaphyseal dysplasia with joint laxity (EXOC6B-SEMD-JL) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with EXOC6B-SEMD-JL, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity: Recommended Evaluations Following Initial Diagnosis

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 summarized in are recommended.

Table 6.

EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity: Recommended Surveillance

System/Concern | Evaluation | Frequency

Joint manifestations

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 spondyloepimetaphyseal dysplasia with joint laxity.

8 publications have been identified in PubMed for spondyloepimetaphyseal dysplasia with joint laxity. Research spans Basic Science / Preclinical (50%), Case Report / Case Series (25%), and Review / Meta-Analysis (13%).

Recent Publications

Šemić A (2026). [PMID: 41959455](https://pubmed.ncbi.nlm.nih.gov/41959455/). *bioRxiv*. [Basic Science / Preclinical]
Chand K (2026). [PMID: 42068746](https://pubmed.ncbi.nlm.nih.gov/42068746/). *Biochem Biophys Res Commun*. [Basic Science / Preclinical]
Zamanian Najafabadi S (2025). [PMID: 40751525](https://pubmed.ncbi.nlm.nih.gov/40751525/). *Archives of Iranian medicine*. [Case Report / Case Series]
Upadhyai P (2025). [PMID: 40395934](https://pubmed.ncbi.nlm.nih.gov/40395934/). *Front Cell Dev Biol*. [Review / Meta-Analysis]
Jacob P (2025). [PMID: 39706863](https://pubmed.ncbi.nlm.nih.gov/39706863/). *Eur J Hum Genet*. [Epidemiology / Natural History]

Data assembled from 4 of 12 sources · Last updated Sep 20, 2026, 5:38 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:93359

GARD

Genetic and Rare Diseases Info Center

GARD:4982

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

Feature	Proportion of Persons w/Feature	Comment
Clinical manifestations	Joint dislocations	7/7
Joint laxity	7/7	—
Short stature1	5/7	Postnatal onset
Slender fingers	7/7	—
Genu valgum	6/7	—
Pes planus	4/7	—
Spine manifestations	6/7	Scoliosis, kyphosis, short neck, /or hyperlordosis
Barrel-shaped chest	2/7	—
Radiographic findings	Delayed carpal bone ossifications	7/7
Gracile, short tubular bones (leptodactyly)	6/7	—
Metaphyseal dysplasia	6/7	—
Epiphyseal dysplasia	6/7	—
Slender ribs	4/7	—
Irregular vertebral end plates	3/7	—
Narrow interpedicular distance of lumbar vertebrae	3/7	—
Platyspondyly	2/7	1. Joint manifestations. All reported individuals have joint dislocations at birth; hip and knee joints are affected in all individuals. Other joints that are often dislocated include elbows, wrists, and ankles. The patella can also be dislocated.

GeneReviews

Differential Diagnosis

Table 3. Common Conditions with Multiple Joint Problems (Laxity, Dislocations, Restriction of Joint Movement) in the Differential Diagnosis of EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity

Gene	Disorder1	MOI	Clinical Findings	Imaging Findings
B3GALT6	SEMD-JL (Beighton type), B3GALT6-related(OMIM 271640)	AR	Prenatal-onset short stature; Facial dysmorphism (oval face, prominent forehead, prominent eyes, blue sclera, micrognathia, cleft palate); Progressive kyphoscoliosis joint dislocation	Progressive kyphoscoliosis; Ovoid vertebral bodies; Severe platyspondyly; Short, flared iliac wings; Radioulnar dislocation
B3GAT3	Multiple joint dislocations,short stature, craniofacial dysmorphisms, skeletal dysplasia ± heart defects, B3GAT3-related(OMIM 245600)	AR	Short stature; Brachycephaly, prominent forehead; Multiple joint dislocations; Cardiac anomalies	Scoliosis; Occasionally modest platyspondyly; Dislocation of radioulnar interphalangeal joints; Broad ilia; Long phalanges w/relatively short metacarpals; Occasionally generalized osteoporosis
B4GALT7	Ehlers-Danlos syndrome, spondylodysplastic type 1 (EDSSPD1), B4GALT7-related(OMIM 130070)	AR	Short stature; Broad, flat forehead; Joint laxity dislocations; Long, slender fingers toes; Loose elastic skin	Scoliosis; Large joint dislocation; Radioulnar synostosis
CANT1	Desbuquois dysplasia,CANT1-related(OMIM 251450)	AR	Prenatal-onset short stature; Midface hypoplasia; Joint dislocations	Occasionally, multiple coronal clefts of vertebral bodies; Advanced carpal ossification; Monkey wrench femora; Hyperphalangy of index finger
CHST3	Chondrodysplasia w/congenital joint dislocations,CHST3-related(See CHST3-Related Skeletal Dysplasia.)	AR	Short stature; Joint dislocations /or restriction of joint movement; Clubfeet; Kyphoscoliosis	Multiple coronal clefts of vertebral bodies; Increase in interpedicular distance from T12 to L1 or L2; Bifid distal humerus; Accessory carpal ossification centers
GZF1	Joint laxity, short stature, myopia (OMIM 617662)	AR	Short stature; Severe myopia; Joint dislocation laxity	Osteopenia; Progressive kyphoscoliosis
KIF22	SEMD-JL (Hall type or leptodactylic type),KIF22-related(OMIM 603546)	AD	Short stature; Knee/hip joint dislocation; Midface hypoplasia; Joint laxity; Genu valgum; Velvety skin; Hypotonia	Progressive scoliosis; Vertebral dysplasia (modest platyspondyly in younger persons); Epimetaphyseal dysplasia (small, flat epiphyses irregular metaphyses w/longitudinal striations); Gracile, short tubular bones
NIN	SEMD-JL (leptodactyly-like phenotype)2	AR	Microcephaly; Primordial short stature; Flat facial features; Joint laxity; Joint dislocation; Genu valgum; Pes cavus	Scoliosis; Squared ve...

Source: GeneReviews — "EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity"

System/Concern	Evaluation	Comment
Cardiovascular	Echocardiography	For routine cardiac eval
Genetic counseling	By genetics professionals1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of EXOC6B-SEMD-JL to facilitate medical personal decision making Family support resources
EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity: Recommended Surveillance System/Concern	Evaluation	Frequency
Joint manifestations	Assessment of joints by rheumatologist or orthopedic surgeon	Annually Scoliosis/Kyphosis

spondyloepimetaphyseal dysplasia with joint laxity

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Joint manifestations

Research Landscape

Recent Publications

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Guidance

Clinical Trials

Scoliosis/Kyphosis