Hand syndromesHolt–Oram Syndrome
Section snippets
Etiology
Transcription factor TBX5, a key factor in limb and cardiac development,3 with a gene locus at 12q24.1, has been linked to Holt–Oram syndrome. More than 70 mutations in the TBX5 gene (Online Mendelian Inheritance in Man no. 601620) resulting in a haploinsufficiency have been associated with Holt–Oram syndrome. However, only 35% of cases of Holt–Oram syndrome can be linked to such mutations.4 In addition, neither the genotype nor the location of the mutation determines the phenotype in Holt–Oram
Presentation
Patient presentation to the hand surgeon varies, typically depending on the presence or absence of a family history. In families with a parent with Holt–Oram syndrome, the diagnosis may have been suggested by prenatal ultrasound6 and confirmed after birth, before presentation to the hand surgeon. However, when Holt–Oram syndrome presents spontaneously, patients often come to the hand surgeon with an apparent upper extremity birth anomaly. This may seem to be isolated to the limb(s) because
Upper limb
The clinical presentation of limb deficiency in Holt–Oram syndrome is variable, but most patients are on the spectrum of RLD. The thumb is often involved although not universally. When affected, the thumb is typically either absent or hypoplastic, but may be different from other hypoplastic thumbs and often is not classifiable by traditional grading systems. The thumb may be triphalangeal, syndactylized to the index ray, or have a finger-like appearance (5-finger hand), resting in the plane of
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Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome
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