Seven patients with Smith-McCort dysplasia 2: Four novel nonsense variants in RAB33B and follow-up findings

Smith-McCort dysplasia 2 (SMC2) is a rare spondylo-epiphyseal-metaphyseal dysplasia caused by biallelic RAB33B variants. Short trunk dwarfism and radiological findings including the lacy ilia appearance and double bumps of the vertebral bodies are typical features. To date, only eight patients with SMC2 had been reported. The aim of this study is to evaluate the follow-up findings of seven patients from five families with SMC2 and to present four novel variants in RAB33B. The age of diagnosis of the patients was between 4 and 18 years. All patients had variable degrees of short trunk dwarfism with barrel chest, waddling gait, hyperlordosis, genu valgum, elbow and finger joint stiffness, which became more evident with growth. Lacy iliac crest, short ilia with basilar hypoplasia, platyspondyly, dysplastic acetabulum with small and/or laterally displaced femoral heads, and small, irregular carpal bones were detected on skeletal radiographies of all patients. Typical double hump appearance of vertebral bodies was present in patients under 12 years of age, which disappeared after puberty and development of elongated vertebral bodies was also observed. At the time of diagnosis, six patients were able to walk independently; patients who were followed for five to nine years, developed severe hip pain, hip and knee joints stiffness and difficultly of walking after 10 years of age. Only two patients could walk independently during final examination. We detected four novel nonsense variants (p.Gln85Ter, p. Cys48Ter, p. Arg94Ter and p. Gln134Ter) in RAB33B. This study provides important data on long-term skeletal findings of the patients with SMC2