Biallelic loss of function variants in EXOC6B gene causes spondyloepimetaphyseal dysplasia with joint laxity, type 3 (SEMDJL3). Major clinical characteristics associated with SEMDJL3 are:
Multiple joint dislocations involving elbow, hip, and knee can be observed. Joint laxity, irregular vertebral end plates, mild platyspondyly, kyphosis, scoliosis, lumbar lordosis, narrow interpedicular distance, slender ribs, osteopenia, slender metacarpal and metatarsals can be noted. Epiphyseal dysplasia and metaphyseal cupping, widening or irregularities can be evident.
Additionally, short neck, barrel chest, genu valgum, bilateral flat feet, short 3rd, 4th, and 5th toes and prominent heels are common. Difficulty in walking can be seen in all affected individuals.
Facial features such as broad forehead, overhanging columella, small chin may be appreciated in certain individuals.
In one affected individual, intellectual disability and central nervous system anomalies including hydrocephaly, hypoplastic mesencephalon and thin corpus callosum were noted.
EXOC6B