Academic journal article Genetic Counseling

Severe Rhizomelic Chondrodysplasia Punctata in a Fetus Due to Maternal Mixed Connective Tissue Disorder

Academic journal article Genetic Counseling

Severe Rhizomelic Chondrodysplasia Punctata in a Fetus Due to Maternal Mixed Connective Tissue Disorder

Article excerpt

Summary: Severe rhizomelic chondrodysplasia punctata in a fetus due to maternal mixed connective tissue disorder: Maternal systemic lupus erythematosus and autoimmune diseases have been extremely rarely reported to cause rhizomelic chondrodysplasia punctata. We report on a fetus aborted spontaneously at 21 weeks of gestation due to complications of maternal mixed connective tissue disorder. The fetus had micrognathia, a depressed nasal bridge, flat nose, long philtrum, short columella and rhizomelia. Radiographic study showed stippling of carpal and tarsal bones, short humeri and coronal clefts in the vertebrae. Ossification centers were present at the lower end of the femora and upper end of the tibiae.

Key-Words: Rhizomelic chondrodysplasia punctatea Mixed connective tissue disorder - Autoimmune disease - Stippling - Antinuclear antibody.


Chondrodysplasia punctata is a heterogeneous group of rare familial, genetic or non-genetic disorders of the skeleton characterized radiographically by punctate calcifications in the epiphyseal regions of endochondral bone formation. Rhizomelic chondrodysplasia punctata is an autosomal recessive disorder caused by peroxisomal dysfunction. It is characterized by severe rhizomelia of limbs along with punctate calcification, coronal clefts in thoracic and lumbar vertebrae, microcephaly, delayed growth, psychomotor retardation, spasticity and early death. They also show micrognathia, malar hypoplasia and flattened bridge and bulbous tip of the nose. Genetic defects are seen in the PEX7 gene leading to defective biosynthesis of plasmalogens and defective degradation process of phytanic acid (12). Apart from peroxisomal dysfunction, the other causes of rhizomelic chondrodysplasia punctata include exposure to teratogens (warfarin, rubella, dilantin, oral anticoagulants) and maternal conditions (autoimmune disease, phenylketonuria) (3, 7, 8). The first publication of the association of chondrodysplasia punctata with maternal autoimmune connective tissue disorder was by Costa et al. in patients with systemic lupus erythematosus (4). We report a fetus with rhizomelic chondrodysplasia punctata born to a woman with mixed connective tissue disorder.


A 25-year-old primigrávida with a non-consanguineous marriage was referred for worsening of hypertension at about 18 weeks of pregnancy. She was noted to have hypertension at 8 weeks of gestation. Her hemoglobin was 9.0 g/dL (12.0-15.0 g/dL) and platelet count was 10.0?103/µ? (150-400?103/µ?). She was diagnosed to have autoimmune hemolytic anemia, secondary anti-phospholipid antibody syndrome (APLA), hypothyroidism (TSH level >100 µ??/mL, reference range: 0.7-7.0 µ??/mL) and mixed connective tissue disorder. Anti ribonucleoprotein (anti RNP), anti-Smith (anti-Sm) and anti-Sjogren Syndrome A (anti-SSA) antibodies were detected in the serum. She had proteinuria. Complement C3 and C4 levels were low in the serum. She was started on prednisolone 60 mg/day, azathioprine 100 mg/day and L-thyroxine 100 µ/day. Ultrasound findings at 19 weeks of gestation showed all long bones to be shorter than the 5th percentile, intrauterine growth retardation, a hypoplastic nasal bone and absence of umbilical artery flow. Fetal echocardiography was normal. She had a spontaneous abortion at 21 weeks of gestation.

The fetus was sent for evaluation. The study has the approval of ethics committee of the institute. The male fetus weighed 280 g (less than 10th percentile), measured 18 cm (26.2, +/-3.6 cm) and head circumference was 17 cm (3"1 percentile). Dysmorphic features included micrognathia, a depressed nasal bridge, flat nose, long philtrum and short columella (Fig. 1A). Bilateral severe rhizomelic shortening of the upper limbs with arm and forearm measuring 2 cm and 3 cm respectively were observed (Figs IB and 1C). Fingers were short with bulbous tips (Fig. IB). Radiographic studies revealed extensive stippling across the entire skeleton, pronounced at the carpal and tarsal bones, bilateral short humeri and coronal clefts in the vertebrae (Fig. …

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