Brachydactyly

Brachydactyly is most commonly caused by genetic mutations in one of several known genes. Brachydactyly type A1 is caused by mutations in Indian hedgehog (IHH), type A2 by mutations in bone morphogenetic protein receptor (BMPR1B), type A3 by mutations in homeobox D13 (HOXD13), type B by mutations in receptor tyrosine kinase–like orphan receptor 2 (ROR2), and type C by mutations in cartilage-derived morphogenetic protein 1 (CDMP1). Brachydactyly types D and E can also be caused by genetic mutations in HOXD13. 

These genes are involved in the complex signaling pathways that regulate the growth and development of bones in the hands and feet. Brachydactyly is typically inherited in an autosomal dominant pattern where only one copy of the mutated gene needs to be passed on from a parent to cause the disorder. However, an autosomal recessive inheritance pattern (i.e. two copies of the mutated gene have to be passed down for the disorder to occur) can be seen in some cases of brachydactyly type B. Brachydactyly can also be a feature in individuals with genetic syndromes, such as Down syndrome (trisomy 21), Rubinstein-Taybi syndrome, and Turner syndrome. In rare cases, certain types of isolated brachydactyly (i.e., not seen as part of a syndrome) can be caused by medications taken during pregnancy, including thalidomide, which was used in the past for nausea during pregnancy; warfarin (i.e., an anticoagulant); retinoids (e.g., isotretinoin); and anticonvulsants (e.g., valproate, carbamazepine).  

The signs and symptoms of brachydactyly can differ depending on the type.  

Type A brachydactyly is subdivided into three subtypes: type A1 affects the middle phalanges, leading to shortened middle fingers or toes; type A2 affects the middle phalange of the index finger and occasionally the little finger; and type A3 affects the middle phalanx of the little finger. 

Type B brachydactyly results in shortened distal phalanges of the fingers and toes and occasionally underdeveloped nails. Type C is characterized by the shortening of the index, middle, and small fingers of the hand. Type D brachydactyly primarily affects the thumbs, resulting in shortened distal phalanges of the thumbs, giving them a broad or “clubbed” appearance. While the big toe may also be affected, type D brachydactyly is more commonly noted in the thumbs. 

Lastly, in type E brachydactyly, there is a general shortening of the metacarpal and/or metatarsals, which connect the fingers and toes to the wrist and ankles, respectively. In type E brachydactyly, the phalanges are also frequently involved.  

Generally, brachydactyly results in shortened fingers and/or toes, affecting all fingers and toes or just a few. This results in disproportionately small/short fingers or toes compared to the hands and feet; and the shape of the toes can also be abnormal, appearing more broad or cone-shaped. In some cases, brachydactyly affects joint mobility, which may result in impaired fine motor skills and an inability to grasp objects. Some may have nail abnormalities on the affected fingers or toes. Additionally, while the shortened bone structure associated with brachydactyly typically does not cause pain and discomfort alone, the abnormal bone structure may predispose an individual to excess stress on the joints and osteoarthritis, thereby resulting in joint stiffness and pain.