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Cardiofaciocutaneous (CFC) syndrome associated with muscular coenzyme Q 10 deficiency
Author(s) -
Aeby A.,
Sznajer Y.,
Cavé H.,
Rebuffat E.,
Van Coster R.,
Rigal O.,
Van Bogaert P.
Publication year - 2007
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-007-0612-0
Subject(s) - costello syndrome , noonan syndrome , coenzyme q10 , endocrinology , hypotonia , medicine , myopathy , ataxia , mitochondrion , biology , cancer research , genetics , mutation , kras , neuroscience , gene
Summary The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes ( PTPN11 , HRAS , KRAS , BRAF , MEK1 and MEK2 ), involved in the mitogen‐activated protein kinase (MAPK) pathway, have been identified in CFC–Costello–Noonan patients. Coenzyme Q 10 (CoQ 10 ), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. CoQ 10 deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to CoQ 10 supplementation. We report the case of a 4‐year‐old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular CoQ 10 deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after CoQ 10 treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for CoQ 10 biosynthesis. Another hypothesis is that K‐Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that CoQ 10 might contribute to the pathogenesis of CFC syndrome.