Rhizomelic Chondrodysplasia Punctata

Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal recessive peroxisomal disorder of plasmalogen synthesis, with proximal limb shortening, epiphyseal stippling, congenital cataracts, severe growth failure and profound developmental delay. Type 1, caused by PEX7 variants, is the commonest.

Pathophysiology. Plasmalogens are ether phospholipids required for myelin, membrane function and bone development. Type 1 (PEX7) impairs the import of enzymes needed for plasmalogen synthesis and phytanic acid breakdown. Types 2 to 5 involve GNPAT, AGPS, FAR1 and PEX5 (long isoform) and affect plasmalogen synthesis alone.

Phytanic acid builds up only in type 1.

Milder variants cause attenuated disease, with survival into adolescence.

• Rhizomelia (shortening of the humerus and femur) and short stature
• Epiphyseal and extra-skeletal stippling on radiographs
• Coronal clefts of vertebral bodies, and metaphyseal cupping
• Congenital bilateral cataracts
• Flat facial profile, a broad nasal bridge, and microcephaly
• Joint contractures
• Severe developmental delay, hypotonia and spasticity
• Seizures, recurrent respiratory infections and respiratory failure
• Feeding difficulty and poor growth
• Ichthyosis in some
• Milder phenotype: milder rhizomelia, cataracts and mild to moderate intellectual disability

• Red cell plasmalogen levels: reduced in all types.
• Plasma phytanic acid: raised in type 1 but may be normal in early infancy.
• PEX7 sequencing, or panel testing for GNPAT, AGPS, FAR1 and PEX5, with deletion and duplication analysis.
• Skeletal survey to show stippling and rhizomelia.
• Ophthalmology review for cataracts.
• Prenatal ultrasound: shortened proximal limbs in the second trimester.

Differential diagnosis.

• Zellweger spectrum disorder
• X-linked chondrodysplasia punctata (CDPX2, EBP) and CHILD syndrome
• Warfarin embryopathy and maternal vitamin K deficiency
• Maternal autoimmune disease with stippling
• Other short limbed skeletal dysplasias

• Respiratory care: chest physiotherapy, vaccination, prompt treatment of infection and supplemental oxygen as needed. Respiratory failure is the usual cause of death.
• Feeding and growth: dietitian input, high energy feeds and gastrostomy.
• Cataracts: early surgery within the first months of life where vision can be improved.
• Orthopaedic and joint care: physiotherapy and surgical release for contractures where function will improve. Cervical spine assessment before anaesthesia.
• Seizures: levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily. Provide a rescue plan: buccal midazolam 0.3 mg/kg (maximum 10 mg) for a seizure lasting over 5 minutes.
• Phytanic acid restriction: a low phytanic acid diet in type 1 with raised levels, which excludes dairy fat, ruminant meat and some fish.
• Skin care: emollients for ichthyosis.
• Development and communication: early intervention and physiotherapy.
• Palliative care: early involvement in severe disease, with symptom relief.
• Genetic counselling: a 25% recurrence risk in each pregnancy, with prenatal diagnosis available.

Special groups.

• Children with milder disease: plan long term follow up of cataracts, growth, hearing and neurology.

Monitoring. Growth and respiratory status at each visit. Eye review every 6 months, phytanic acid levels as treatment indicates, and development every 6 months.

Referral and escalation. Refer to clinical genetics, metabolic medicine, respiratory paediatrics and ophthalmology. Emergency for respiratory distress or aspiration.