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severe spondylodysplastic dysplasia - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

severe spondylodysplastic dysplasia

MONDO:0800080

Overview

An instance of spondylodysplastic dysplasia that has a high degree of severity.

OnsetANTENATAL

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: before birth.

GeneReviews

Clinical Guidance

INPPL1-related opsismodysplasia is characterized by prenatal-onset short stature, short limbs, small hands and feet, narrow thorax, dysmorphic facial features (including relative macrocephaly, prominent forehead, midface retrusion, depressed nasal bridge, short nose, anteverted nares, and relatively long philtrum), delayed epiphyseal mineralization, metaphyseal cupping, and platyspondyly. To date, 35 individuals have been identified with biallelic pathogenic variants in INPPL1 [, , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. INPPL1-Related Opsismodysplasia: 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

INPPL1-related opsismodysplasia should be suspected in a proband with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

Prenatal-onset disproportionate short stature with short limbs
Characteristic facial features (relative macrocephaly, prominent forehead, midface retrusion, depressed nasal bridge, short nose, anteverted nares, and a relatively long philtrum)

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 severe spondylodysplastic dysplasia. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

No clinical practice guidelines have been published for INPPL1-related opsismodysplasia. Recommended initial evaluations, treatment, and surveillance are adapted from case reports and best practice guidelines for skeletal dysplasia management [, , , , , , ]. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with INPPL1-related opsismodysplasia, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. INPPL1-Related Opsismodysplasia: 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. INPPL1-Related Opsismodysplasia: Recommended Surveillance

Data assembled from 2 of 12 sources · Last updated Sep 19, 2026, 6:47 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

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?

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Feature	% of Persons w/Feature	Comment
Short stature	10/10	—
Short long bones	15/19	Long bones are often bowed.
Short hands/feet	18/20	—
Delayed epiphyseal mineralization	18/20	—
Metaphyseal cupping	17/20	—
Platyspondyly	13/18	—
Small/narrow thorax	7/19	—
Renal phosphate wasting/ hypophosphatemia	7/10	—
Respiratory issues	15/20	Prenatal. Reported prenatal ultrasound findings reflect the underlying skeletal differences, including short limbs, short long bones, short hands and feet, narrow thorax, bell-shaped thorax, platyspondyly, and decreased bone echogenicity.

GeneReviews

Differential Diagnosis

Biallelic pathogenic variants in INPPL1 were identified in approximately 60% of individuals with opsismodysplasia in one cohort . The genetic etiology has not been identified in some individuals with clinical findings consistent with opsismodysplasia . Table 3. Genes of Interest in the Differential Diagnosis of INPPL1-Related Opsismodysplasia

Gene(s)	Disorder	MOI	Features of Disorder
COL1A1/2 osteogenesis imperfecta	AD	Short stature, short limbs, osteopenia, fractures, limb malalignment, platyspondyly, respiratory insufficiency	Wormian bones lack of other skeletal findings assoc w/INPPL1-related opsismodysplasia; No renal phosphate wasting/ hypophosphatemia
COL2A1	Type II collagen disorders (severe to moderately severe phenotypes)	AD1	May be lethal in perinatal period; Short stature, short limbs, platyspondyly, cervical instability, epiphyseal delay, metaphyseal cupping
Osteoglophonic dysplasia	AD	Short stature, short limbs, brachydactyly, metatarsal irregularity, lower extremity bowing, platyspondyly; Renal phosphate wasting/ hypophosphatemia	Craniosynostosis, non-ossifying bone lesions, unerupted/retained teeth FGFR3
Thanatophoric dysplasia	AD	Often lethal in perinatal period; Short stature, short limbs, brachydactyly, platyspondyly, narrow chest, relative macrocephaly	Cloverleaf skull, foramen magnum narrowing, severely bowed femurs, trident hand; No renal phosphate wasting/ hypophosphatemia
FAM111A	Osteocraniostenosis (See FAM111A-Related Skeletal Dysplasias.)	AD	Often lethal in perinatal period; Short stature, short limbs, metaphyseal flaring, brachydactyly, bone fractures
GPX4	Severe spondylometaphyseal dysplasia (Sedhaghatian type), GPX4-related (OMIM 250220)	AR	Short stature, delayed ossification/ epiphyseal delay, brachydactyly, small hands/feet, short long bones, metaphyseal cupping, platyspondyly, narrow chest
PAM16	Spondylometaphyseal dysplasia, PAM16-related (OMIM 613320)	AR	Short stature, delayed ossification, short long bones, metaphyseal cupping, platyspondyly, small chest

Source: GeneReviews — "INPPL1-Related Opsismodysplasia"

System/Concern	Evaluation	Comment
Cardiac	Echocardiogram	—
Renal	Renal ultrasound	ENT
Genetic counseling	By genetics professionals1	To obtain a pedigree inform affected persons their families re nature, MOI, implications of INPPL1-related opsismodysplasia to facilitate medical personal decision making Family support resources

severe spondylodysplastic dysplasia

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Prognosis

Surveillance Guidelines

Medical References

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Clinical Trials