Case report: severe hypertrophic cardiomyopathy in a female neonate caused by

Background: Hypertrophic cardiomyopathy in the neonate has a diverse genetic background, and non-sarcomeric variants may not be identified on commercial genetic testing panels. NDUFB11 is an X-linked mitochondrial Complex I protein and is known to cause histiocytoid cardiomyopathy but has not been described in female infants with hypertrophic cardiomyopathy. We present this first reported case of obstructive hypertrophic cardiomyopathy in a female neonate secondary to a pathogenic variant in NDUFB11. Case summary: A term female neonate presented following a prenatal diagnosis of biventricular hypertrophy and growth restriction. She developed lactic acidosis after birth and whole-genome sequencing identified a Discussion: Hemizygous variants in NDUFB11 have been associated with hypertrophic cardiomyopathy in male infants previously, and skewed X-linked inactivation likely resulted in the presentation described here in a female infant. This variant was not identifiable by commercial cardiomyopathy panels. We highlight the importance of rapid whole-genome sequencing in cases of infantile hypertrophic cardiomyopathy and the importance of genetic diagnosis in guiding prognosis and care for these individuals.