Muscular involvement intheHolt-Oram syndrome

Holt-Oramsyndromeisan autosomal dominantdisorder characterised by radialray and congenital heartdefects. Recently, a gene forthisdisorder hasbeen identified on chromosome12q24.1, encodinga T boxtranscription factor. However, thefunctional roleofthegene productis not completely understood. We present results ofneurological, radiological, and muscle magneticresonance imaging (MRI)investigations in13patients from eightunrelated families. Besidesheart defects, clinical signsrangedfromthenar abnormalities to bilateral phocomelia. The formerwere presentinallpatients. MRI showedhypoplasia ofdiscrete muscleswhichclinically showed as nonprogressive weakness.The structural patternofresidual muscles was normalon MRI,whichtogether withnormalmuscularpower, electromyography, andmuscle enzyme investigations excluded a progressiveneuromuscular disorder. Thenumber andlocation ofhypoplastic musclescorrelatedwiththeseverity ofskeletal involvement. Thus,patients withhypoplasia of largeand proximalmuscleshad phocomelia,andthosewithmere intrinsic hand musclehypoplasia had onlya triphalangealthumb or no skeletal malformation. On thebasisoftheseobservations, we conclude thatdisturbed fetal limbmuscle developmentis involvedin the bony malformations oftheupper limbs. (7MedGenet1997;34:978-981)