A Case of Opsismodysplasia with a Novel INPPL1 Variant.

Introduction: Opsismodysplasia is a rare autosomal recessive genetic skeletal disorder characterized by short stature, short limbs, small hands and feet, delayed bone age, severe platyspondyly, metaphyseal cupping, and facial dysmorphism. Opsismodysplasia is caused by biallelic variants in the INPPL1 gene. Only 38 patients with a confirmed molecular diagnosis have been reported so far.

Case presentation: We present a 9-month-old male patient who was referred to our clinic with a suspicion of mucopolysaccharidoses due to facial features and radiographic findings, but urine glycosaminoglycans were within normal ranges. Audiologic and ophthalmologic assessments, transfontanelle ultrasound, and echocardiography were all normal. A renal cortical cyst with a diameter of 33 × 28 mm was detected in abdominal ultrasound. He had dysmorphic findings including relative macrocephaly, midface hypoplasia, depressed nasal bridge, anteverted nostrils, long philtrum, small hands and feet, and brachydactyly. His length was 63 cm (-3.7 SD) and his arm span was 58 cm. Delayed bone age, short metacarpals and phalanges, wide and irregular metaphysis, platyspondyly, anterior beaking of the vertebrae, T12 vertebral hypoplasia, and acetabular dysplasia were noted on X-rays. Exome sequencing revealed a novel homozygous c.147C>G (p.Ser49Arg) variant in INPLL1.

Conclusion: Opsismodysplasia is an extremely rare skeletal disorder, and with this case, we further expand the clinical and molecular spectrum of opsismodysplasia.