Rhizomelic Chondrodysplasia Punctata Type 1
Rhizomelic chondrodysplasia punctata or RCDP encompasses a group of pathologies characterized by shortening of the long bones, cataracts, periarticular calcifications, multiple joint contractures and psychomotor retardation.
Rhizomelic chondrodysplasia punctata rhizomelica type 1 (RCDP1), which is the most common RCDP, accounting for 90% of patients, follows an autosomal recessive mode of inheritance and is caused by pathogenic variants in the PEX7 gene. This gene is indispensable in peroxisomal metabolism, so that certain variants in PEX7 can alter the transport of certain enzymes into the peroxisome and affect the synthesis of plasmalogens, a type of phospholipids that make up the cell membrane.
The prevalence of RCDP1 is estimated to be 1 in 100,000 individuals.
Symptoms
In the classic form of RCDP1 the first symptoms occur at birth or in the first months of life. It is a severe disease in which the survival rate after 10 years is low.
Symptoms include:
- Proximal shortening (rhizomelia) of the humerus and to a lesser extent of the femur.
- Punctate calcifications in cartilage (chondrodysplasia punctiformis).
- Coronal clefts of the vertebral bodies.
- Reduced birth weight, length, and head circumference
- Seizures
- Severe intellectual deficit
- Stunted growth
- Cataracts
Cases have been described with less severe symptomatology, similar to that seen in patients with Refsum disease, such as retinitis pigmentosa, sensory motor polyneuropathy and ichthyosis.
Disease management
Treatment of patients with RCDP1 focuses on relieving symptoms and improving their quality of life. Physiotherapy is used to improve contractures and orthopedic procedures. Dietary restriction of phytanic acid in order to prevent its accumulation. Surgery to recover part of the vision and pharmacological treatment with anticonvulsants for epileptic seizures.
Genes analyzed
Bibliography
Braverman NE, Steinberg SJ, Fallatah W, et al . Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
Duker AL, Niiler T, Kinderman D, et al . Rhizomelic chondrodysplasia punctata morbidity and mortality, an update. Am J Med Genet A. 2020 Mar;182(3):579-583.
Fallatah W, Schouten M, Yergeau C, et al . Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata. J Inherit Metab Dis. 2021 Jul;44(4):1021-1038.
Luisman T, Smith T, Ritchie S, et al . Genetic epidemiology approach to estimating birth incidence and current disease prevalence for rhizomelic chondrodysplasia punctata. Orphanet J Rare Dis. 2021 Jul 6;16(1):300.
Motley AM, Brites P, Gerez L, et al . Mutational spectrum in the PEX7 gene and functional analysis of mutant alleles in 78 patients with rhizomelic chondrodysplasia punctata type 1. Am J Hum Genet. 2002 Mar;70(3):612-24.
