Bone Abstracts

Background: Pathogenic mutations in thyroid hormone receptor interactor 11 (TRIP11) have previously been associated with achondrogenesis1A, a lethal autosomal recessive skeletal dysplasia. Recent findings have suggested that hypomorphic mutations of TRIP11 result in odontochondrodysplasia (ODCD), a rare syndrome associated with spondylometaphyseal dysplasia and dentinogenesis imperfecta.

Presenting problem: This is the case of a term female born to non-consanguineous parents with an unidentified skeletal dysplasia. Short bones were initially detected on a third trimester antenatal ultrasound. While her birth weight was 3 kg (25th–50th centile) by the age of 3.5 years her weight and height are less than the 0.4th centile while her OFC is above the 91st centile. She exhibits mesomelia, genu valgum, a small thoracic diameter with pectus carinatum and lumbar lordosis. She has hypermobile joints and flat feet. She has white sclera, dentinogenesis imperfecta but no history of fractures. Developmentally, she has a normal intellect and met her milestones appropriately apart from gross motor delay in walking at 2.5 years of age. Radiologically, she has evidence of congenital platyspondyly, vertebral coronal clefts, relatively long fibulae and valgus deformity of the femoral necks.

Clinical Management: The clinical diagnosis of ODCD was made in the first year of life through consultation with the European skeletal dysplasia network. Genetic screening for mutations in the achondrogenesis 3-gene panel confirmed a heterozygous mutation for the TRIP11 gene (c.1314+1G?A(;)3082C>T) in early 2019. Our index case receives ongoing multidisciplinary input from respiratory, dental and developmental paediatrics as well as routine bone health surveillance. Her family have been referred for genetic counselling in light of the postulated recessive nature of this condition.

Discussion: ODCD is a rare skeletal dysplasia which has only recently been ascribed to hypomorphic mutations of TRIP11 gene. TRIP11 is essential for endochondral ossification. Our case exhibits the dental changes characteristic of DI but no evidence of polycystic renal disease or obstructive hydrocephalus. This is the first case reported of ODCD due to a TRIP11 mutation in Ireland. This diagnosis will enable the family to link with other affected families and provide shared knowledge essential for surveillance and follow-up.

Disclosure: The authors declared no competing interests.