Chondrodysplasia With Joint Dislocations, gPAPP Type

Introduction

Chondrodysplasias are a group of genetic conditions that affect the development of bones. Chondrodysplasia with joint dislocations, gPAPP type, is a type of chondrodysplasia known as gPAPP deficiency. It is a rare hereditary condition with a prevalence of less than one in one million individuals.

What Is Chondrodysplasia With Joint Dislocations, gPAPP Type?

Chondrodysplasiawith joint dislocations, gPAPP type, is a rare genetic disorder that causes bone dysplasia that starts as early as the prenatal period. It is characterized by short stature, congenital joint dislocations, shortened limbs, and many other skeletal malformations.

What Causes Chondrodysplasia With Joint Dislocations, gPAPP Type?

• Chondrodysplasia with joint dislocations, gPAPP type, is caused due to changes in the genetic material (mutations) of an individual. These genetic mutations are inherited in most cases.

• It has been found that chondrodysplasia with joint dislocations, gPAPP type is due to the homozygous mutations in the IMPAD1 gene. The IMPAD1 gene is present in the 8q12 chromosome.

• The mode of inheritance of this condition is autosomal recessive. The autosomal recessive pattern means an individual must inherit two copies of the mutated gene, one from each parent, to develop this condition. If an individual inherits one copy of the mutated gene, they are considered carrier and usually unaffected by the condition.

What Are the Risk Factors for Chondrodysplasia With Joint Dislocations, gPAPP Type?

• This is a genetic disorder. Therefore the primary risk factor is having a family history of the condition.

• Individuals with a parent or sibling with GPAPP-type chondrodysplasia may be at an increased risk of developing the condition.

• This condition may occur sporadically in some cases, meaning there is no known family history. However, even in these cases, the risk of developing the condition is likely to be influenced by genetic factors.

What Are the Symptoms of Chondrodysplasia With Joint Dislocations, gPAPP Type?

Symptoms of this condition start appearing as a newborn and infant. Symptoms can vary in severity from person to person, and not all individuals with the condition will exhibit all of the symptoms.

• Short stature with height less than normal as for the age and gender norms.

• Abnormalities of the head and neck - Individuals affected by this condition have various dysmorphic facial features like

  • High forehead.

  • Flat face.

  • Cleft palate (separation of the roof of the mouth)

  • Narrow mouth.

  • Short nose with a broad nasal bridge.

  • Proptosis refers to eyes that are protruding more than normal.

• Abnormalities of the limbs - Chondrodysplasia with joint dislocations, gPAPP type cause many skeletal deformities in the hands and legs of the affected individuals. Some of the abnormalities related to hands and legs are

  • Short metacarpals.

  • Brachydactyly.

  • Short foot and toes.

  • Abnormalities in the bones of the fingers and toes, like supernumerary carpal ossification centers, short metacarpals, and varying sizes of the metacarpal epiphyses.

  • Genu valgum, also known as knocked knees, is a condition in which the knees are turned inward and are closer together.

• Abnormalities of the musculoskeletal system include

  • Micrognathia refers to an underdeveloped mandible.

  • Patellar (kneecap) dislocation.

  • Coronal craniosynostosis (premature closure of the coronal suture in the skull).

• Other rare symptoms that may be seen include

  • Hearing impairment.

  • Mild psychomotor delay.

  • Scoliosis.

  • Recurrent joint dislocations.

  • Short neck and breathing problems.

How Is Chondrodysplasia With Joint Dislocations, gPAPP Type Diagnosed?

• Diagnosis of this condition is made through physical examination and other imaging studies.

• Genetic tests are used to confirm the diagnosis.

• A physical examination may reveal symptoms like short stature, joint dislocations, and other skeletal abnormalities.

• X-rays and other imaging studies may also evaluate bone and joint structures.

• The patient's medical history can provide important clues, particularly if there is a family history of similar symptoms or if the individual has experienced recurrent joint dislocations.

• Since gPAPP deficiency is a rare condition, seeking a medical specialist with experience in diagnosing and managing rare genetic conditions is essential.

What Are the Complications of Chondrodysplasia With Joint Dislocations, gPAPPType?

• Recurrent joint dislocations can cause chronic pain, instability, and joint damage over time, which may lead to early-onset osteoarthritis.

• Short stature can lead to social and psychological challenges and also cause medical challenges like spinal cord compression and breathing difficulties.

• Limb deformities can cause difficulty with mobility and fine motor skills and an increased risk of fractures and joint damage.

• Delayed motor and cognitive development may occur in some cases.

• Congenital heart defects and other cardiovascular abnormalities may be present in rare cases.

How Is Chondrodysplasia With Joint Dislocations, gPAPP Type Treated?

No specific treatment plan is available for this condition, and treatment is aimed at managing symptoms and complications. Treatment may involve a combination of medical and surgical interventions and is often tailored to an individual's specific needs.

Medical management.

• Physical therapy can help with joint mobility, muscle strength, and coordination.

• Pain medications are prescribed to help in managing joint pain and discomfort.

• Assistive devices like braces, splints, and other devices may help stabilize joints and improve mobility.

• Respiratory support, such as supplemental oxygen or mechanical ventilation, may be necessary to address breathing difficulties.

Surgical management.

Surgical interventions are needed for chondrodysplasia with joint dislocations, gPAPP type, when the symptoms of the affected individuals do not improve with medications and other conservative approaches. Some of the surgical management procedure done include

• Joint reconstruction surgeries may be done for severe joint dislocations or deformities.

• Spinal fusion is a surgery to repair scoliosis in which the affected vertebrae are fused together to correct the curved spine.

• Limb lengthening surgeries are sometimes required to lengthen the limbs and correct discrepancies in bone length.

Genetic counseling

Geneticcounseling is an essential aspect of the management of gPAPP-type chondrodysplasia. Genetic counseling can help individuals and families understand the genetic basis of the condition, assess their risk of having a child with the disorder and explore options for genetic testing and family planning.

Conclusion

Appropriate management and support may help individuals with chondrodysplasia with joint dislocations, gPAPP type, to manage their symptoms and live fulfilling lives. The affected individuals must work closely with their healthcare providers to develop an individualized treatment plan and monitor for potential complications.