Edition of 11 August 2017

In a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia, the authors identified a homozygous truncating variant in GZF1 through a combined autozygome and exome approach. The same approach identified a second homozygous truncating GZF1 variant in another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement. The authors suggested that GZF1 mutations cause a phenotype of severe myopia and significant articular involvement not previously described in Larsen syndrome.

The authors described two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalised nuclei, myofibrillar disarray, and "corona" fibres. Both affected siblings were found to be compound heterozygous for mutations in SCN4A on exome sequencing, and the parents were confirmed carriers of one of the mutations.