EP07.05: Prenatal diagnosis of geleophysic dysplasia with ADAMTSL2 mutations

Geleophysic dysplasia (GD) is an autosomal recessive disorder featuring short stature, brachydactyly, distinctive facial appearance, hepatomegaly, cardiac valvular disease, and bronchopulmonary insufficiency. This disease is rarely described prenatally. We present a case of GD in 22 weeks with brachydactyly, typical facial appearance, cardiac and pulmonary anomalies and confirmed by genetic testing and gross examination. A 27-year-old primigravida was referred to our centre at 22+4 weeks gestation due to suspected fetal abnormalities. No significant family history was noted. Chorionic villus sampling showed two heterozygous mutations in a ADAMTSL2 gene-NM_014694.4: c.502G>A (p.G168S) and NM_014694.4: c.763G>C (p.A255P). According to the guidelines, both variants are regarded as variants of uncertain significance (VUS). Mutations in ADAMTSL2 are known to be associated with Type 1 GD. Detailed ultrasound was undertaken to further detail the fetal phenotype. Detailed ultrasound showed that the fetal long bones were between 2-3 standard deviations below the mean. Bilateral brachydactyly, fixed drop feet and thickened skin were observed. Facial features appeared as upturned corners of the fetal mouth and low-set ears. Thickening of the fetal ventricular myocardium (3~4mm) and a hypoechoic, inhomogeneous echo in the fetal lungs were noted. The nuchal fold was mild thickening. The head and abdominal circumference were within the normal range. The association of ultrasound findings and genotype support the diagnosis of GD. After counselling the prognosis, patient opted for termination of the pregnancy. Postmortem examination confirmed the prenatal ultrasound findings. In this case, both variants are regarded as VUS. Two missense ADAMTSL2 variants in this case may add to the list of causative mutations resulting in type-1 GD. And prenatal ultrasound assessment of the fetal phenotype helps us to better interpret fetal genotype and find the potential causative variants.