Pseudoachondroplasia Presentation and Treatment

Last Updated on May 16, 2025

Pseudoachondroplasia is a rare, inherited skeletal disorder characterized by disproportionate short stature, affecting approximately 1 in 30,000 individuals.

It belongs to the skeletal dysplasias group and is also called pseudoachondroplastic spondyloepiphyseal dysplasia (PSACH).

Although it resembles achondroplasia in limb shortening, pseudoachondroplasia is a genetically and clinically distinct condition.

Unlike achondroplasia, pseudoachondroplasia is not typically evident at birth[1]. Most affected children appear normal during infancy, and characteristic features such as short-limbed dwarfism, ligamentous laxity, and gait abnormalities emerge between 2 and 3 years of age.

Facial features, head size, and intelligence remain normal, helping differentiate it from other forms of disproportionate short stature.

The average adult height is markedly reduced: males typically reach around 119 cm (3 feet 11 inches), and females about 114 cm (3 feet 9 inches). Despite the growth limitation, most individuals maintain normal cognitive function and lead fulfilling lives with supportive care and appropriate orthopedic management.

This article outlines the genetic basis, clinical presentation, radiological findings, differential diagnosis, and treatment approaches for pseudoachondroplasia. A comparison with achondroplasia is also included to help clarify diagnostic distinctions.

Pseudoachondroplasia affects males and females in equal numbers.

Genetics and Pathogenesis

Pseudoachondroplasia is primarily caused by mutations in the COMP gene [2](Cartilage Oligomeric Matrix Protein), located on the short arm of chromosome 19 (19p13.1).

The COMP protein is essential for the normal development and structural integrity of cartilage, especially in the growth plate during endochondral ossification.

COMP functions as an extracellular calcium-binding protein involved in maintaining the structural framework of cartilage by interacting with collagen types II, IX, and XI.

In pseudoachondroplasia, mutations in the COMP gene result in misfolded COMP protein, which is retained inside the rough endoplasmic reticulum of chondrocytes instead of being secreted. This accumulation causes cellular stress and chondrocyte apoptosis (cell death), leading to disorganization of the growth plate and impaired bone elongation.

The inheritance pattern is typically autosomal dominant.

Around 70% of cases arise from de novo mutations, meaning they occur spontaneously without a prior family history. The remaining 30% are familial.

In rare instances, the condition results from germline mosaicism, where one parent carries the COMP mutation in a subset of their reproductive cells, while their somatic cells are unaffected. These parents are clinically normal but may have more than one affected child.

Clinical Presentation

The clinical features of pseudoachondroplasia are typically absent at birth and begin to emerge between 2 and 4 years of age, as linear growth falters and characteristic musculoskeletal signs develop.

Typically, the growth rate lags behind the standard growth curve by approximately two years, leading to a moderately severe form of disproportionate short-limb short stature [1].

The early delay in diagnosis distinguishes it from achondroplasia and many other skeletal dysplasias that are apparent in the neonatal period [3]

General Growth Features

• Normal birth length and appearance
• Progressive short-limbed dwarfism (particularly rhizomelic shortening — upper arms and thighs)
• Average adult height:
  • Males ~119 cm
  • Females ~114 cm

Craniofacial Features

• Normal facial appearance
• Normal head circumference
• No frontal bossing or midface hypoplasia (vs achondroplasia)

Axial Skeleton

• Exaggerated lumbar lordosis
• Thoracolumbar kyphosis (in some cases)
• Scoliosis may develop in late childhood or adolescence
• Odontoid hypoplasia with potential atlantoaxial instability, increasing risk for cervical myelopathy

Lower Limbs

• Waddling gait with delayed walking
• Knee deformities like genu varum, genu valgum, or recurvatum
• Hip stiffness and decreased abduction
• Short femoral necks with coxa vara (decreased neck shaft angle)
• Valgus deformity of the foot, sometimes with medial rotation of the limb

Upper Limbs

• Trident-shaped hands (resembling achondroplasia)
• Short fingers, especially metacarpals and phalanges
• Limited elbow extension
• Shoulder subluxation and decreased range of motion
• Wrist laxity with ulnar deviation

Joint and Muscular Symptoms

• Ligamentous laxity, particularly in the wrists and knees
• Joint incongruity in major joints (hip, shoulder, elbow, knee)
• Early-onset joint pain, stiffness, and degenerative arthritis, especially in adolescence or early adulthood

Neurological and Intellectual Features

• Normal intelligence
• Neurological complications may arise if cervical instability is present

Diagnosis

The diagnosis of pseudoachondroplasia is primarily clinical, supported by radiographic findings and confirmed through genetic testing when needed [1].

Because early signs may be subtle, diagnosis often occurs after walking begins and limb shortening or gait abnormalities become noticeable.

Clinical Indicators

• Onset between 2–4 years of age
• Disproportionate short stature with normal head and facial features
• Waddling gait, joint laxity, and delayed motor milestones
• No intellectual impairment

Radiological Findings

Spine

• Platyspondyly (flattened vertebral bodies) with anterior “beaking”
• Thoracolumbar kyphosis or scoliosis
• No change in interpedicular distance on AP view (helps differentiate from achondroplasia)
• Odontoid hypoplasia, potentially causing atlantoaxial instability

Hips and Pelvis

• Abnormal acetabular roof formation
• Coxa vara with shortened femoral necks
• Irregular, flattened epiphyses and widened metaphyses

Lower Limbs

• Knee epiphyses are fragmented and irregular
• Fibula longer than tibia, often with distal fibular overgrowth
• Genu valgum or varum is commonly seen
• Short, broad metaphyses with joint incongruity

Hands and Wrists

• Short metacarpals and phalanges
• Blunt metaphyseal ends
• Wrist ulnar deviation may be present

Advanced Imaging

• MRI/CT spine: Helpful in assessing spinal cord compression, especially at the cervicomedullary junction
• MRI hip/knee: Evaluates joint congruency and early arthritic changes

Genetic Testing

Molecular analysis of the COMP gene confirms the diagnosis by identifying pathogenic mutations. It is recommended in

• Equivocal cases
• For family counseling
• Prenatal diagnostic planning

Laboratory Testing

This is more of a research tool than a diagnostic tool. The circulating COMP protein levels are significantly reduced and may support diagnosis in research settings.

Prenatal Diagnosis

Chorionic villus sampling (CVS) or amniocentesis can detect known familial COMP mutations when indicated by family history.

Differential Diagnosis

Pseudoachondroplasia shares overlapping features with other skeletal dysplasias, [3] particularly short-limb dwarfism. Therefore, a careful differential diagnosis is essential for accurate classification and counseling.

Achondroplasia

It is the most common differential. Distinguishing features are

• Achondroplasia presents at birth, while pseudoachondroplasia appears after age 2–3
• o Facial features: Achondroplasia shows frontal bossing and midface hypoplasia; pseudoachondroplasia does not
• Achondroplasia shows decreasing interpedicular distance caudally in the lumbar spine, whereas pseudoachondroplasia shows normal distance

Multiple Epiphyseal Dysplasia (MED)

It is also caused by COMP mutations (in some subtypes). The following features help to distinguish

• Milder short stature
• Less pronounced metaphyseal changes
• Later onset of symptoms
• Often, more joint pain than visible deformity

Spondyloepiphyseal Dysplasia (SED)

This includes congenital and tarda types. The distinguishing Features are

• Greater spinal involvement
• Often includes vision and hearing abnormalities (depending on subtype)
• Short trunk, as opposed to short limbs

Other Skeletal Dysplasias to Consider

• Metaphyseal Chondrodysplasia: Presents with metaphyseal irregularities, lacks the epiphyseal, metaphyseal flaring and cupping, especially around the knees
• Morquio syndrome: Short stature with mucopolysaccharidosis features
• Hypochondroplasia: Milder achondroplasia variant
• Diastrophic dysplasia: Associated with ear swelling, hitchhiker thumbs

Normal facies, delayed onset, short limbs, and epiphyseal/metaphyseal irregularities with normal intelligence should raise strong suspicion for pseudoachondroplasia.

Treatment and Management

Management of pseudoachondroplasia is individualized and symptom-directed. While there is no cure for the underlying genetic defect, early orthopedic interventions, physical therapy, and long-term monitoring can significantly improve quality of life and function.

Non-Surgical Management

Physical Therapy

It aims to maintain joint range of motion and strengthen supporting musculature, especially around the hips, knees, and spine. Physical therapy helps prevent contractures and compensatory gait patterns

Pain Management

NSAIDs or analgesics may be prescribed during adolescence or adulthood to manage joint discomfort. [1]

Weight management is important to reduce the load on affected joints

Bracing

Bracing is used for progressive scoliosis (e.g., Milwaukee brace). Bracing my help temporarily in knee valgus/varus deformities during the early stages

Genetic Counseling

Genetic counselling is essential for affected individuals and families. Families should be made aware of inheritance, recurrence risk, prenatal options, and psychological impact. [1]

Surgical Management

Surgery is often required to address significant limb deformities, instability, or neurological compromise.

Spinal Surgery

• Atlantoaxial fusion: It is indicated in cases of cervical instability due to odontoid hypoplasia.
• Scoliosis surgery: It is rarely needed but considered for severe, progressive curves not responding to bracing.

Limb Realignment

• Osteotomies around the knee: Upper tibia, lower femur osteotomies alone or combined can be performed for genu varum, valgum, or recurvatum
• Hip osteotomies: To address hip subluxation or degenerative changes
• Fibular epiphysiodesis: May be needed in cases of distal fibular overgrowth contributing to ankle valgus

Joint Preservation or Replacement

• Early-onset osteoarthritis, especially in the hips and knees, may require surgical intervention in adulthood.
• Joint replacement is considered only when conservative measures fail and function is severely compromised.

Monitoring and Long-Term Care

• Regular spinal imaging, especially in children with cervical spine involvement
• Functional assessments for walking, pain, and posture.
• Psychosocial support is needed during adolescence to address body image, social interaction, and adaptive challenges.[1]

Prognosis and Long-Term Outlook

The long-term prognosis for individuals with pseudoachondroplasia is generally favorable regarding lifespan and cognitive development. The intelligence remains unaffected.

However, quality of life may be influenced by progressive joint symptoms, orthopedic deformities, and spinal complications if not appropriately managed.

Growth and Adult Function

Most individuals achieve independent ambulation, normal schooling, and cognitive development, though final height remains significantly reduced.

Musculoskeletal Outcomes

Early-onset osteoarthritis is common in the hips, knees, and spine and may lead to functional limitations with age, requiring assistive devices or joint replacement

Spinal issues such as kyphosis, scoliosis, and atlantoaxial instability need lifelong monitoring. Cervical spine instability can lead to serious complications such as myelopathy.

Psychosocial Aspects

Social and emotional support during childhood and adolescence is important due to visible short stature and potential mobility challenges. Vocational support and ergonomic adjustments may be beneficial in adulthood.

Overall, with appropriate orthopedic management, physical therapy, and genetic counseling, individuals with pseudoachondroplasia can lead active, independent lives with a life expectancy close to normal.

Pseudoachondroplasia vs. Achondroplasia

Though historically considered variants of the same disorder, pseudoachondroplasia and achondroplasia are now considered distinct skeletal dysplasias with different genetic causes, clinical presentations, and radiological findings.

The main features of both are compared below.

Pseudoachondroplasia differs from achondroplasia in both genetics and clinical presentation, with normal facial features, later onset, and more joint-related symptoms. Accurate differentiation is critical for genetic counseling and orthopedic planning.

Conclusion

Pseudoachondroplasia is a rare but clinically significant skeletal dysplasia marked by postnatal onset of short stature, joint laxity, and progressive orthopedic complications. Despite early normal appearance, children typically develop symptoms by age 2–3, including a waddling gait, lower limb deformities, and spinal curvature. The condition is caused by mutations in the COMP gene, and diagnosis is based on clinical evaluation, radiographic findings, and molecular testing when needed.

Early diagnosis and a multidisciplinary management approach — combining physical therapy, orthopedic intervention, and genetic counseling — are essential to optimize outcomes. Long-term prognosis is favorable in terms of cognitive function and lifespan, but mobility and joint health require proactive monitoring and care.

Understanding the differences between pseudoachondroplasia and other forms of dwarfism, such as achondroplasia or multiple epiphyseal dysplasia, is essential for accurate diagnosis, treatment planning, and family education.

Recent Research and Advances in Pseudochondroplasia

Recent research has provided significant insights into the pathogenesis and potential management strategies for pseudoachondroplasia.

A study in 2023 reported two novel COMP mutations through whole-exome sequencing, emphasizing the growing need for precise molecular diagnostics in differentiating pseudoachondroplasia from similar skeletal disorders. [2]

A 2024 review in Pediatrics International highlighted the radiographic overlap between pseudoachondroplasia and other dysplasias, reinforcing the importance of integrated clinical-genetic evaluation. [3]

A 2025 study by Hecht et al. demonstrated that genetic deletion of the CHOP protein in a mouse model reduced joint degeneration and pain, identifying CHOP as a potential therapeutic target for modifying disease progression. [4]

Hecht, Barreda-Bonis, and Posey in 2025 reported notable improvement in joint pain in a child treated with CurQ+ and resveratrol, pointing toward possible supportive roles for nutraceuticals. [5]

Collectively, these advances reflect a shift toward molecularly targeted therapies and personalized care approaches for affected individuals.

References

1. Briggs MD, Wright MJ. COMP-Related Pseudoachondroplasia. 2004 Aug 20 [updated 2023 Nov 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. [PubMed]
2. Zhou L, Chen J, Liu Q, Yang S, Xie W, Peng Y. Case Report: Whole-exome sequencing identified two novel COMP variants causing pseudoachondroplasia. Front Endocrinol (Lausanne). 2023 Nov 23;14:1267946. [PubMed ]
3. Matsumoto, H., Hori, T., Mori, M., Sasai, H., & Ohnishi, H. (2023). Pseudoachondroplasia: Similar radiographic findings to mucopolysaccharidosis. Pediatrics International, 66(1), e15799. https://doi.org/10.1111/ped.15799
4. Hecht, J. T., Veerisetty, A. C., Hossain, M. G., Patra, D., Carrer, M., Chiu, F., Relic, D., Jafar-nejad, P., & Posey, K. L. (2025). Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia. International Journal of Molecular Sciences, 26(1), 16. [PubMed]
5. Petryka, L., & Ordak, M. Genetic variations in pseudoachondroplasia: A review of case reports. Laboratory Medicine. https://doi.org/10.1093/labmed/lmae121
6. Hecht JT, Barreda-Bonis AC, Posey KL. CurQ+ With Resveratrol Diminish Joint Pain in a Child With Pseudoachondroplasia: A Case Report. Cureus. 2025 Mar 25;17(3):e81195. doi: 10.7759/cureus.81195. [PubMed]