Carey-Fineman-Ziter syndrome (CFZS) is an autosomal recessive inherited disorder. Clinically, patients are described as having non-progressive congenital myopathy with marked facial weakness, together with other clinical attributes such as Moebius and Pierre Robin sequence, facial abnormalities, and growth delay. Recently, autosomal recessive mutations in the gene myomaker (MYMK/TMEM8C) were found to be associated with CFZS. MYMK is a plasma transmembrane protein and is necessary for the fusion of mononuclear myoblasts to multinucleate myocytes in the skeletal muscle.This study describes the long-term clinical follow-up in 3 siblings affected with CFZS due to biallelic mutations in MYMK. All the siblings had a marked and characteristic facial weakness and variable dysmorphic features affecting the face, hands, and feet, and short stature. They had experienced muscle hypotonia and generalized muscle weakness since early childhood. The muscle biopsies revealed, as the only major abnormality at all ages, a marked hypertrophy of both type 1 and type 2 fibers with more than twice the diameter of that in age-matched controls. Genetic analysis revealed biallelic mutations in the MYMK gene, a novel c.235T>C; p.(Trp79Arg), and the previously described c.271C>A; p.(Pro91Thr). This study expands the genetic and clinical spectrum of MYMK mutations and CFZS.
