IllnessHolt-Oram syndrome, differential diagnosis

NGS +

Holt-Oram syndrome (HOS) is characterized by skeletal abnormalities of the upper limbs (especially carpal bones, missing or finger-like thumbs, missing bones in the forearms, etc.) and cardiac problems. Some 75% of these patients have cardiac conditions that can be life-threatening, such as atrial or ventricular septal defects, conduction abnormalities and fibrillation. HOS features are similar to those of Duane radial ray syndrome, for example, and several other conditions that should be considered in the differential diagnosis. HOS is inherited in an autosomal dominant manner, with 85% of affected individuals having a pathogenic variant de novo. Sequencing of the TBX5 gene reveals the HOS mutation in >70% of cases. Differential diagnostic analysis of other genes significantly increases the yield. Nevertheless, a negative DNA result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1111/

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• Alias: Atriodigital dysplasia type 1
• Alias: Heart-hand syndrome type 1
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Allelic: Hutchinson-Gilford progeria (LMNA)
• Allelic: Limb-girdle muscular dystrophy, "LGMD1R" (LMNA)
• Allelic: Lipodystrophy, familial partial, type 2 (LMNA)
• Allelic: Malouf syndrome (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Restrictive dermopathy, lethal (LMNA)
• Duane-radial ray syndrome (SALL4)
• Heart-hand syndrome, Slovenian type (LMNA)
• IVIC syndrome (SALL4)
• Thrombocytopenia-absent radius syndrome (RBM8A)
• Townes-Brocks branchiootorenal-like syndrome (SALL1)
• Townes-Brocks syndrome 1 (SALL1)
• Ulnar-mammary syndrome (TBX3)