A Variant in SLC25A4 Leads to Mitochondrial DNA-Depletion Syndrome-12A Causing Neonatal Hypotonia and Hypoventilation

Abstract

Congenital hypotonia and hypoventilation is a rare association. We report a rare case of a female newborn with poor respiratory drive, ventilator dependency, severe hypotonia, cardiomyopathy, and premature death. Clinical-exome-sequencing revealed SLC25A4-related mitochondrial deoxyribonucleic acid (DNA) depletion syndrome-12A (cardiomyopathic type). This syndrome is apparent at birth and carries a poor prognosis.

Keywords

neonatal hypotonia - hypoventilation - cardiomyopathy - infant - newborn

Authors' Contributions

All the authors took part in clinical management and manuscript preparation.

Publication History

Received: 07 November 2020

Accepted: 22 December 2020

Article published online:
02 February 2021

• References

• 1 Mercuri E, Pera MC, Brogna C. Neonatal hypotonia and neuromuscular conditions. Handb Clin Neurol 2019; 162: 435-448
• 2 Paro-Panjan D, Neubauer D. Congenital hypotonia: is there an algorithm?. J Child Neurol 2004; 19 (06) 439-442
• 3 Bishara J, Keens TG, Perez IA. The genetics of congenital central hypoventilation syndrome: clinical implications. Appl Clin Genet 2018; 11: 135-144
• 4 Finsterer J, Zarrouk-Mahjoub S. Phenotypic spectrum of SLC25A4 mutations. Biomed Rep 2018; 9 (02) 119-122
• 5 Thompson K, Majd H, Dallabona C. et al. Recurrent de novo dominant mutations inSLC25A4 cause severe early-onset mitochondrial disease and loss of mitochondrial DNA copy number. Am J Hum Genet 2016; 99 (04) 860-876
• 6 American Academy of Pediatrics committee on fetus and newborn; American College of Obstetricians and Gynecologists committee on obstetric practice. The Apgar Score. Pediatrics 2015; 136: 819-822
• 7 Richards S, Aziz N, Bale S. et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424