Rhizomelic Chondrodysplasia Punctata - Causes, Symptoms and Management

Introduction:

The hereditary condition known as rhizomelic chondrodysplasia punctata (RCDP) is extremely uncommon and manifests in neonates. A lack of peroxisomal enzyme activity is the underlying cause of this condition. Patients who have RCDP have a lack of acyl-CoA in their bodies, which prevents their bodies from being able to produce plasmalogens. The body possesses high quantities of phytanic acid, an additional biochemical feature associated with RCDP. The degree of the disease as well as the abnormalities of the brain match the severity of the plasmalogen (It is a brain-enriched phospholipid. These lipids formed acted as antioxidants.) reduction that has been observed. As well, the individuals that have the less severe phenotype possess erythrocytes that have considerably larger concentrations of plasmalogens.

There are three distinct subtypes of genetic structure. Those who have mutations in both copies of their PEX7 genes make up type 1, also known as a compound heterozygous mutation. This is the most numerous category. Mutations in the GNPAT gene are responsible for causing type 2 diabetes. Mutations in the AGPS gene cause type 3 to arise. There has been a substantial reduction in life span.

What Are the Associated Comorbidities With Rhizomelic Chondrodysplasia Punctata?

• Heart conditions present at birth.

• Pulmonary hypoplasia.

• Recurrent respiratory tract infections.

• Contractures.

• Atrophic changes in the cerebral and cerebellar regions, together with the expansion of the ventricles and CSF (cerebrospinal fluid) gaps.

• Ureteropelvic junction blockage.

• G-tubes are prevalent owing to aspiration and poor feeding.

• Epilepsy.

• Bilateral cortical cataracts.

What Are the Diagnostic Methods of Rhizomelic Chondrodysplasia Punctata?

Biochemical and molecular genetic studies, in addition to examinations based on clinical observations, are among the diagnostic procedures for the RCDP.

• Biochemical Testing: Plasmalogen deficiency of red blood cells, the elevated plasma level of phytanic acid when the diet contains phytanic acid sources and normal plasma concentration of very long chain fatty acids (VLCFA) have accurately estimated the PEX7 receptor loss in type 1 rhizomelic chondrodysplasia.

Plasmalogen concentrations can differentiate between classic and milder rhizomelic chondrodysplasia punctata type 1: erythrocyte plasmalogen levels are ten to 30-fold greater in milder rhizomelic chondrodysplasia punctata type 1 than in classic rhizomelic chondrodysplasia punctata type 1.

• Molecular Genetic Testing: Molecular genetic testing is conducted with the intent to identify the sequence encoding the PEX7 gene. This is the sole variation that has been linked to RCDP1 that is currently known. In a comparable pattern, the genetic codes for those mutant genes have been determined for every other type.

A diagnosis of rhizomelic chondrodysplasia punctata can be made based on these results when considered in conjunction with the distinctive clinical appearance of the condition.

What Are the Symptoms of Rhizomelic Chondrodysplasia Punctata?

• Type 1 Classical Rhizomelic Chondrodysplasia Punctata - Classic rhizomelic chondrodysplasia punctata type 1 is characterized by skeletal deformities, cataracts, development limitation, and cognitive dysfunction. Rhizomelic chondrodysplasia punctata reduces life span. The majority of deaths were due to respiratory problems. Some babies may expire in the neonatal phase; congenital cardiac dysfunction or lung hypoplasia were related to their death.

• Type 1 Non-classic Rhizomelic Chondrodysplasia - The majority of people with non-classic rhizomelic chondrodysplasia punctata type 1 have bilateral cataracts, various joint contractures, and cognitive deficits in early life.

The symptoms include the following:

• Skeletal Abnormalities - The humerus and femur are bilaterally shortened in infants with type 1 rhizomelic chondrodysplasia. Typically, infants with this condition have contractures and painful, inflexible joints, resulting in irritability. In MRIs (magnetic resonance imaging) of children with type 1 classic rhizomelic chondrodysplasia, the patients showed cervical stenosis along with an increase in the prevalence of global spinal stenosis, cervical kyphosis, and thoracolumbar kyphosis.

The elbows, knees, and hips of the majority of patients with mild rhizomelic chondrodysplasia punctata type 1 exhibit flexion contractures, resulting in reduced voluntary movement. The radiographic finding of chondrodysplasia punctata is frequently observed at the time of a rhizomelic chondrodysplasia punctata type 1 diagnosis, but rhizomelic limb shortening is rare. Coxa vara and an undersized femoral are deformities of the hip joints. To enhance movement, the individuals require orthopedic surgery.

• Cataracts - Almost all affected individuals get bilateral cortical cataracts. These are typically persistent and apparent at birth or throughout the initial few months following birth for severe type 1.

The majority of people who are diagnosed with mild rhizomelic chondrodysplasia punctata type 1 have cataracts identified in both eyes during the initial two years of their lives.

• Restriction on the Rate of Growth - A substantial developmental shortage is present throughout the average lifespan, even though birth weight, length, and head circumference are frequently within the lower range of the normal. Weight gain is quite slow.

The growth of individuals with mild rhizomelic chondrodysplasia punctata type 1 is normal. The postnatal growth rates are superior to those of type 1 classic rhizomelic chondrodysplasia.

• Intellectual Impairment - The majority of children diagnosed with rhizomelic chondrodysplasia punctata severe type 1 reach their early developmental milestones at later ages.

The majority of people with mild rhizomelic chondrodysplasia punctata type 1 have developmental problems and learning impairments. Individuals suffering from mild rhizomelic chondrodysplasia punctata type 1 are capable of walking and are able to converse vocally.

• Seizures - Myoclonic jerks are the most common type of seizure that is documented; however, the incidence and types of seizures can vary considerably.

Absence and tonic-clonic seizures were the most prevalent types of seizures in the mild (non-classic) group.

• Respiratory Tract Illnesses - A combination of cognitive impairment, aspiration, immobility, and a small chest with limited expansion leads to frequent infections of the respiratory tract. Plasmalogen insufficiency potentially causes long-term respiratory disease as lipids are abundant in the lung and an essential element of surfactant.

• Congenital Heart Abnormalities - Individuals have cardiac anomalies. In the majority of cases, septal abnormalities, tetralogy of Fallot, and peripheral pulmonary stenosis were reported. Mitral valve prolapse, eczema, minor ichthyosis, and rashes on the skin were also noticed. Individuals affected were observed with ureteropelvic junction blockage, cleft palate, diaphragmatic hernia, hypospadias, and cryptorchidism.

Imaging of the brain reveals atrophy of the cerebral and cerebellar regions, along with enlargement of the ventricles and CSF gaps. Progressive atrophy of the cerebellum. MRI and MR spectroscopy have revealed delayed myelination, signal anomalies in supratentorial white matter, lower choline-to-creatine ratios, and elevated levels of mobile lipids, which are believed to suggest a shortage of plasmalogens, which are essential components of myelin.

Individuals with mild rhizomelic chondrodysplasia punctata type 1 were found to have cardiac abnormalities involving atrial septal defects and mitral valve prolapse, indicating heart degeneration.

• Pigmentary Retinopathy and Peripheral Neuropathy - In non-classical type1, individuals showed developmental problems and poor growth; in puberty, retinitis pigmentosa and peripheral neuropathy manifested.

What Are the Treatment Methods for Rhizomelic Chondrodysplasia Punctata?

Several birth defects and a poor prognosis are treatment constraints, which are both supportive and limiting. Inadequate food consumption and recurring aspiration may require the installation of a gastrostomy tube, with emphasis on pulmonary function and pulmonary evacuation. The removal of cataracts improves considerable vision. Some individuals require orthopedic operations to improve their functionality and physiotherapy to treat contractures. Standard treatment for developmental disabilities and intellectual disabilities.

Type 1 classic (severe) rhizomelic chondrodysplasia punctata is managed with supportive therapy due to many birth defects and poor prognosis. Orthopedic operations have been performed on children diagnosed with a minor form of rhizomelic chondrodysplasia punctata type 1 to preserve their gait and joint mobility.

• Primary Intervention - Individuals with mild rhizomelic chondrodysplasia punctata type 1 benefit from limiting their intake of phytanic acid through their nutrition to prevent the negative effects of the phytanic acid collection over time.

• Management Therapy for the Motor System - Physical therapy is indicated for maximizing function and reducing the risk of future orthopedic issues such as contractures, scoliosis, and hip dislocation. Medical devices and positioning devices, such as wheelchairs, walkers, bath chairs, orthotics, and adaptive strollers, for the treatment, are essential.

• Fine Motor - For deficits in fine motor abilities and difficulties with fine motor skills that impact adaptive roles, including such difficulties in eating, grooming, clothing, and writing, occupational therapy is advised.

• Oral Motor - Choking or gagging throughout feedings, poor weight gain, regular respiratory ailments, and feed intake denial are all indicators that oral motor dysfunction is prevalent. Oral motor dysfunction should be evaluated periodically, and clinical feeding evaluations and radiographic swallowing studies should be acquired when these symptoms are present. It is advised to receive feeding treatment from an occupational or speech therapist to help improve coordination or sensory-related feeding disorders. An NG tube or a G-tube may be required in cases of significant malfunction in the feeding process.

• Ineffective Communication - Individuals struggling with their ability to express themselves verbally could benefit from having an assessment completed for alternate ways of communication, such as augmentative and alternative communication, with the help of a speech-language pathologist. Equipment for augmentative and alternative communication can vary from basic methods, such as picture exchange communication, to highly technical methods, including voice-generating devices. Augmentative and alternative communication technologies, according to a common misconception, do not hinder the development of verbal speech and can rather assist in enhancing it.

• Challenges With Behavior and Social Norms - Structured behavior analysis and other treatments for autism spectrum disorder may be appropriate for and beneficial for children with non-classic rhizomelic chondrodysplasia punctata type 1. A board-certified behavior analyst often works personally with a child during applied behavior analysis (ABA) treatment to address both their behavioral, social, and adaptive strengths and limitations.

The prescription drugs, such as those used to treat attention-deficit hyperactivity disorder, may be given to parents with the support of a pediatrician and can also guide parents toward the finest behavior management techniques. A pediatric psychiatrist could address issues with dangerously harmful or violent behavior.

• Monitoring - Regular monitoring of growth, nutritional status, and developmental and educational needs should be monitored. Regular evaluations for signs of ingestion, pulmonary inadequacy, seizure management, visual, auditory, joint damage, and orthopedic issues should be carried out.

• Medication - Those who have RCDP are required to receive both the influenza vaccine and RSV monoclonal antibody as preventative measures as a result of their respiratory difficulties. Oral plasmalogen supplementation has also been given to the patient.

Conclusion

In children, rhizomelic chondrodysplasia punctata is an extremely unusual manifestation of the disease. There is no treatment available for rhizomelic chondrodysplasia punctata (RCDP). However, after the age of ten, the majority of children have less chance of survival. The diagnostic technique was primarily obtained through the use of clinical assessment in conjunction with studies such as X-rays. The treatment for RCDP should emphasize relieving symptoms and providing supportive care. In later phases, the treatment may also involve physiotherapy and orthopedic operations designed to improve performance. The child may benefit from cataract surgery to enhance vision.