A case of Rhizomelic chondrodysplasia punctata in a neonate

Figure 1: Skeletal Survey: Significant shortening of humeri with mild metaphyseal flaring distally. Discrete punctate cartilaginous calcifications are present at the proximal and distal humeri.

Javaid HA, Fawzy NA, Mostafa R, and Shehata N. (2022) A case of Rhizomelic chondrodysplasia punctata in a neonate. Cureus.

Rhizomelic chondrodysplasia punctata (RCDP) is an ultra-rare genetic disorder caused by an inability to synthesize plasmalogens. Plasmalogens are a unique class of phospholipids that contain a vinyl-ether bond at the sn-1 position and have many essential roles in cells. They are important structural components of the cell membrane and influence its fluidity, are involved in vesicular fusion and cellular signaling, are major components of lipid rafts, and have antioxidative properties. RCDP can have a range of presentations from severe to intermediate, but is typically characterized by short stature especially in the proximal extremities, punctate calcifications in cartilage, congenital contractures, congenital cataracts, developmental delay, seizures, cardiac abnormalities, chronic respiratory illness, and shortened lifespan. RCDP is also classified into type because of the mutation in the plasmalogen biosynthetic enzyme that causes the disorder. Although the RCDP population is very small, the medical requirements are high and more awareness is necessary for early diagnosis and proper care. Javaid et al are describing the first reported case of RCDP type 1 in the Middle East.

The individual was an 11-day-old female from northern Saudi Arabia born at 36 weeks with an APGAR score of 9 and a at 2.3 kg in weight. She displayed dysmorphic facial features such as low-set ears, depressed nasal bridge, and frontal bossing. The skeletal survey confirmed the shortening of the humeri and femur, discrete punctate cartilaginous calcifications present at the proximal and distal ends of both, and she had flexion contractures at the knees. She was also found to have bilateral medium-density cataracts. The Moro reflex, one of the first primitive reactions to fright that is developed between 28 and 32 weeks of gestation, was weak and unequal in this individual. There were no convulsions or abnormal movements detected; her skin displayed normal pallor and had no lesions; the cardiac, chest, and abdominal evaluations were normal; and the cranial ultrasound with doppler showed normal findings.

The initial diagnosis was made based on the clinical and radiological presentation, but further blood work, metabolic screens, and genetic testing was done to confirm the diagnosis. The blood count and inflammatory markers were typical, and the blood chemistry tests were normal. The metabolic screen for inborn metabolism errors was negative, as were the blood and throat cultures. The individual was found to have a peroxisomal biogenesis factor 7 (PEX7) mutation which encodes the receptor for the first set of peroxisomal matrix enzymes targeted by peroxisome targeting signal 2 (PTS2). Disruptions to the function of this gene results in peroxisomal dysfunction and an inability to produce plasmalogens. This result confirmed the diagnosis of RCDP and specified that it was Type 1.

Javaid et al described an RCDP case in Saudi Arabia of a neonate. She displayed a classic presentation of dysmorphic facial features, shortened proximal limbs, punctate calcifications, and cataracts. Although the diagnosis was assumed following the clinical and radiological examination, genetic testing confirmed that the individual had RCDP Type 1 due to a mutation in PEX7. There are 5 genes within the plasmalogen biosynthetic pathway that can result in RCDP because the dysfunction of any of the five will often entirely prevent the production of plasmalogens and due to their variety of essential roles, its unsurprising their loss has such a strong effect. Because this disorder is so rare, more awareness is needed so that it can be recognized early, like in the case of the individual in this report, and receive proper care, a correct diagnosis, and effective therapy.