EP.121Carey-Fineman-Ziter syndrome: a MYMK-related myopathy mimicking brainstem dysgenesis

Abstract

Carey-Fineman-Ziter syndrome (CFZS) is clinically defined by the combination of hypotonia, Moebius sequence, Robin sequence, facial anomalies, motor delay and growth failure. The etiology has remained elusive, although brainstem dysgenesis has been suggested. Recently CFZS was found to be associated with autosomal recessive mutations in the gene MYMK, which impair the fusion of mononuclear myoblasts to multinucleate myocytes in the skeletal muscle. We report a new case and define the clinical phenotype. The patient was the first boy from non-consanguineous parents. Pregnancy was unremarkable, but at birth he presented with hypotonia and bilateral facial palsy without external ophthalmoplegia. His facial appearance included small nose, retromicrognathia, downslanting palpebral fissures, low-set ears and a high arched palate. He also had feeding difficulties and needed nasogastric tube for a few months. There was generalized joint laxity and global muscular hypoplasia. During the first years of life his motor development was delayed; independent walking was acquired at age 2 and he used the Gowers’ maneuver to come to an upright position. CK levels, nerve conduction study and electromyography were normal. Cranial MRI did not show any abnormalities, but a muscular MRI disclosed mild fatty infiltration of thigh adductors, gluteus and soleus muscles. Nevertheless, a muscle biopsy from quadriceps showed no myopathic features. Genetic testing by Whole-Exome-Sequencing detected two mutations in the MYMK gene: c.271C>A and c.399+5G>A. Nowadays he is 3.5 years old, he has no cognitive impairment and his motor abilities are improving slowly. CFZS is a congenital myopathy with prominent facial involvement, which is a diagnostic clue. There is variability in the pathology findings that may be explained by the muscle selected for biopsy or patient’s age. Clinical course is static or slowly progressive, but the identification of new well characterized genetic cases will help to delineate the complete phenotype.