Background: Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies. One such condition is SMD with corner fractures (OMIM #184255). These individuals generally show development of coxa vara, scoliosis and triangular ossification centers at the edges of metaphyses that simulate fractures.
Presenting problem: To date only 16 patients with SMD and biallelic fibronectin (FN1) mutations have been reported. The majority had a substitution of a cysteine in the N-terminal assembly region. We report a family with a novel missense mutation.
Methods: Analysis of candidate genes by massive parallel sequencing (TruSightTM One Panel, NextSeq Illumina) and data analysis by SeqNext (JSI).
Clinical Management: The novel missense mutation in FN1:c.341G>C (p.Arg114Pro) was inherited from the mother. The girl, born at term BW 1.895 kg (−3, 03 S.D.), L 44 cm (−2,83 S.D.), was first evaluated for short stature and developing waddeling gait at 7 years. Radiographic features were compatible with a bilateral perthes like hip dysplasia, coxa vara, shortened femoral neck, flattened epiphysis with corner fractures, abnormal vertebrae with end-plate irregularities. Height was113,5 cm (−3,5 S.D.) at 8.4 years. The brother was born preterm at 33/3 weeks with normal birth measurements, normal development. At 9 years he developed an abnormal gait caused by unilateral coxa vara. Height was 127.6 cm (P10). The mother was evaluated in her childhood with short stature and coxa vara. Final height was 149 cm. In adulthood she developed painful osteoarthritis and osteonecrosis affecting mainly knees and ankles.
Discussion: The report expands the clinical phenotype and demonstrates familial variability concerning onset and severity of symptoms.
Disclosure: The authors declared no competing interests.