A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice
The proband is an 8 y old male from non-consanguineous family of mixed Ashkenazi Jewish and Caucasian ethnicity. He was born at 38 weeks of gestation via induced vaginal delivery. The prenatal history was significant for intrauterine growth restriction and unilateral multicystic dysplastic kidney. Decreased fetal movement was noted initially at the beginning of the third trimester. His birth weight was 5 pounds 12 ounces (< 5%), and his head circumference was 31 cm (< 5%). After birth he was noted to have bilateral dislocated hips due to an underlying developmental hip dysplasia. He was also noted to have foot abnormalities consistent with talipes cavus and bilateral undescended testicles. The immediate neonatal period was characterized by a prolonged hospitalization, hypotonia and feeding difficulties. MRI of the brain in the newborn period was abnormal demonstrating microcephaly and small thalami with increased intensities in bilateral basal ganglia and thalami. His growth continued to be poor, and he was severely hypotonic and microcephalic. MRI of the brain at the age of 4 y showed evidence of diffuse volume loss with decreased thickness of the white matter and increased ventricular size. The atrophy was also evident in the inferior cerebellar hemispheres and inferior cerebellar vermis. MRI demonstrated a left sided diaphragmatic hernia which has not been repaired with partial herniation of the stomach into the chest. At the age of 8 y he is severely developmentally delayed and microcephalic. He is non-ambulatory and non-verbal. He uses an assistive communication device. He is able to recognize objects and faces. All his feeds are via gastrostomy tube.