Kasuistik: Eineiige Zwillingsschwestern mit gleichem Phänotyp a.e. einer mitochondrialen Erkrankung bis anhin ohne nachweisbare Deletion oder Mutation
Presentation - Jul 4, 2019
Scherrer Michael, Felbecker Ansgar
Since birth, currently 25-year-old monozygotic female twins (otherwise negative family history) suffer from proximal accentuated, symmetrical muscle weakness, fatigue, exercise intolerance, mental retardation in early childhood, ptosis of both eyes and progressive external ophthalmoplegia. There are also vegetative symptoms like chronic obstipation with recurrent stomach pain and urinary retention with spontaneous recovery at the age of 20 as well as a chronic hypohidrosis. Due to frequent periods of apnea during sleep, a congenital central hypoventilation syndrome was diagnosed at the age of four, treated with a Variable Positive Airway Pressure (VPAP) device.
Ophthalmological examination showed retinitis pigmentosa sine pigmento in both twins. In muscle biopsy (2014), an increased variation of fiber thickness and some lobulated fiber profiles were found. However, detailed molecular genetic analysis of the mitochondrial and nuclear genome provided no evidence of deletion or point mutation. Also, a mutation in PHOX2B gene – defining for the congenital central hypoventilation syndrome (CCHS) - was not detectable. Up to now, periodic echocardiography and electrocardiogram were normal.
Monozygotic (identical) twins share the same mitochondrial DNA (mtDNA) from early life, but even in ‘‘identical’’ twins there can be remarkable differences in the levels of mutated mtDNA in different tissues. Therefore, it is possible – like in our case – that both twins are affected by a mitochondrial disease in a similar degree, but also that one of the twins develops a symptomatic mitochondrial disease whereas the other is completely asymptomatic.
The clinical evaluations, diagnostic findings and course of disease are highly suspicious for the same mitochondrial disease in both twins, even if we couldn’t find a causal deletion or mutation yet. Due to negative family history and clinical findings, a sporadic respectively new deletion (or mutation) of mtDNA is most likely, shared as twins in the same oocyte before development of the embryos. No relation between the congenital central hypoventilation syndrome and the mitochondrial disease was described until now. Whole Exome Sequencing (WES) would be useful.