Rhizomelic chondrodysplasia punctata (RCDP) is a rare autosomal recessive disorder characterized by stippled epiphyses and rhizomelic shortening of the long bones within the heterogenous group of chondrodysplasia punctata (1). There are few reports discussing the antenatal diagnosis of RCDP. We report prospective antenatal diagnosis of a case with RCDP in a fetus without family history.
A 30 year old multigravid was referred to our clinic at 29 weeks gestation following ultrasound detection of short femur length. The parents had first degree consanguinity and the family had no history of skeletal dysplasia. Ultrasonographic evaluation revealed that the femur and tibias were below the 3rd centile. Multiple punctuations were detected in proximal and distal epiphyses of the humeri and femur (Fig. la-lb). The remaining long bones were appropriate in length for gestational age. Nasal hypoplasia, micrognatia and increased prenasal thickness were detected in the fetal profile. No additional malformation was detected. Diagnosis of RCDP was suspected due to the findings of stippled epiphyses in the context ofrhizomelic limb shortening. Fetal blood sampling analysis revealed PEX 7 mutation in consistent with Type 1 RCDP. Follow up ultrasonographic examination at 32 weeks 6 days of gestation demonstrated the previous findings detected earlier. Cesarean section (CS) was performed at 39 weeks gestation with the indication of previous CS. Morphologic features of the newborn were flat face, hypertelorim, broad nose, antevert nares, long and smooth philtrum, down turned comers of the mouth, broad ear nodules and short neck (Fig. lc). Postnatal radiographs revealed shortening of the both humeri and femoras and stippling of long bones (Fig. Id).
Since RCDP is inherited in an autosomal recessive manner, there will be a negative family history for most cases. So the diagnosis can be done if a family history exists but cases have been reported even without such a history. Similar to the present case; Gendal et al. reported a case of rhizomelic chondrodysplasia punctata in a dichorionic twin, in which one was noted to have rhizomelic limb shortening at 25 weeks of gestation. The humeri were shaped like dumbbells and multiple hyperechoic foci were noted in the humeral and proximal femoral epiphyses. Diagnosis of rhizomelicchondrodysplasia punctata was confirmed in this twin by demonstration of absent alkyl-dihydroxyacetone phosphate synthase activity in cultured skin fibroblasts after postmortem examination (2). Also Hertzberg et al. described prospective antenatal diagnosis of RCDP in a fetus with no family history. In the light of sonographic findings including rhizomelic shortening in combination with premature ossification and stilliping of multiple epiphyses. Amniosynthesis revealed deficient fibroblast peroxisomal plasmalogen synthesis enzymes, which confirmed the diagnosis (3).
Nasal hypoplasia, micrognatia and increased prenasal thickness were the only additional sonographic findings in the present case. Basbug et al. reported sonographic diagnosis of a case with type 1 RCDP at 30 weeks of gestation with bilateral cataracts (4). Also Sastrowijoto et al. reported a case of RCDP with congenital heart disease (5).
The premature ossification and disordered stippling of the epiphyses in RCDP are characteristic but not unique to the disorder. They can be also found in other forms of chondrodysplasia punctata, aneuploidies, Zellweger syndrome, vitamin K reductase deficiency and teratogen exposures such as warfarin (6,7). Although a range ofother conditions can cause stippled epiphyses, RCDP is distinctive for the profound rhizomelic shortening of long bones and the flaring of metaphyses that are not seen with the other causes of epiphyseal stippling.
In conclusion, RCDP should be kept in mind in fetuses who have ultrasonographic identification of rhizomelic shortening of the long bones in combination with premature ossification and stippling ofthe epiphyses of the long bones and patients need to be offered specific testing for RCDP to verify the clinical impression.
