Saturday, April 3, 2021

Understanding the 'Why' of Upper Extremity Birth Differences Part 1

Birth differences of the upper extremity have many different forms/ presentations. These can be a dramatic with a shortened or deviated extremity or very subtle/ mild with slightly short fingers or a subtle lack of muscle development. In my three decades of caring for kids, it has always been clear that our team is truly caring for the whole family. Families have many questions about what we can do to help their child (surgery, therapy, what the future holds for their child, and the 'why'- why is their chiild, their family affected with this anomaly. The purpose of this blog post is to discuss the last issue, the 'why' of birth differences of the upper extremity. This is part 1 and I will add a part 2 with some specific information about different anomalies. I always share with patients that limb differences are most commonly related to errors to our genetic code- the DNA. This means that there are changes (mutations) in the DNA sequences related to errors in the coding. We believe that some of these are random (just happen), some are clearly a genetic condition (passed from parent to child), and some are caused by external causes that lead to the mutation. This can be related to medication, environment, or other causes of DNA changes. To me, the fact that our bodies get it 'right' as often as they do is really remarkable. I stress that in the vast majority of patients, nothing a parent did caused the mutation in the DNA and nothing they could have done would have prevented this error. This is really, really important because all parents question their "role". Known examples of medications or drugs causing a limb difference are really uncommon. The most striking and perhaps the most understood example of a medication leading to an extremity difference is the drug thalidomide which was given in the 1950s and early 1960s to help prevent nausea of pregnancy. Thalidomide caused dramatic "phocomelia" or limb shortening. I have blogged about this before on several occasions: This is a classic image from Smithsonian magazine.
Our understanding of birth differences continues to grow but it is safe to say that we all want to know more. The first step in understanding why birth differences happen is understanding what normal (or maybe I should say typical) limb development looks like. We know that upper limb development occurs from 26-54 days of gestation- with the upper limb fully formed before the end of the second month of pregnancy (although obviously quite small). There are three axes of development each with each being guided by different proteins, signals, and morphogens. The axes all development and progress simultaneously and NOT independently- there is a complex interaction between these areas. 1) The proximal distal axis 2) The anterior posterior axis (also known as the radial- ulnar axis and the pre-axial- post axial axis) 3) The dorsal- volar axis (top and bottom of the limb and fingers) One of my favorite articles on limb development was written more than 20 years ago and it discusses one of the key morphogens- sonic hedgehog. Robert Riddle and Clifford Tabin share insights which have stood the test of time including the importance of this video game inspired name of a key protein.
There have been many experiments to better understand limb development and some of my favorites use chick embryos. The developing limb can be easily altered to assess the impact of different proteins or areas of the developing limb. Cheryl Tickle has made notable contributions in this field as higlighted . Below I share a few images from my friend and limb development expert Kerby Oberg. Kerby has made so many contributions to the field is a close friend to clinicians who focus on the treatment of kids with limb differences. He is also a part of the team that created the very important and practical classification system for upper limb anomalies- the OMT. We recently updated the classification system as part of a great team.
The proximal distal axis This axis of development is all about the limb growing longer and bigger. The apical ectodermal ridge (AER) is the key area of ectoderm that interacts with the underlying mesoderm to grow the limb. This limb is affected dramatically by TBX5, Wnt3, FGF8 and FGF10.
The anterior posterior axis This axis is guided by sonic hedgehog (as noted above). This protein diffuses across the developing limb and is key for ulnar sided limb development. Too little contributes to ulnar deficiency and extra (especially in a different area) can lead to a mirror hand. Radial deficiency is likely more related to Gli3 but this is a complicated interchange.
The dorsal ventral axis This axis is least well understood and, perhaps, least 'important' to limb development. Classically, we think about LMXb1 as driving the difference in function and appearance between the top and bottom of the fingers.
My next post will be more on what we know about specific conditions and what might go wrong during limb development. Thanks for reading, Charles A. Goldfarb, MD My Bio at Washington University email: Please CLICK HERE to support our research. Designate my name. Thank you!

Saturday, February 6, 2021

Forearm Synostosis- Facts and My Approach to Treatment

 I have previously blogged about forearm synostosis HERE.  A few important points

1) It uncommon compared to other upper extremity anomalies but is perhaps the most common of the forearm birth differences.

2) It is really well tolerated by most children.  Especially because the rest of the upper extremity is typically normal (most importantly, the hand)

3) The function impact depends on a few factors:

The position of the forearm (i.e., how rotated is it)

Whether one arm or both

The child- each child is affected differently

4) It is recognized later than many birth anomalies because it is not immediately obvious. 

It is a bony problem and the forearm can look normal.  Parents often count fingers and toes but, unless the parent is a congenital hand surgeon, parents do not typically test forearm rotation. 

Each of us can "rotate" through our wrists so that it looks like the forearm is rotating.  Unless you actually feel feel the forearm, determining rotation can be tough.

Functional limitations may be few and often do not become obvious until the child is required to perform higher- order tasks (often school age or sports).

When is surgery helpful?

Surgery is not typically required but a few factors increase the likelihood of surgery being helpful.  First, when both forearms are affected it is more difficult for the child to compensate.  And second, when the forearm is fixed in severe rotation (typically palm down/ pronation but can be palm up/ supination).

What is the 'best' surgery?

There are two basic concepts for surgery (and only one works).  

1) The most appealing to every single parent and every single surgeon- restore rotation of the forearm.  That is, take out the bony block and allow the radius and ulna to rotate the forearm.  There have been a huge number of techniques attempted but I want to be clear: these surgeries do not work

2) Position the forearm in a more neutral posture (think clapping position).  This allows shoulder motion to help position the hand and is a highly effective surgery.  This requires cutting and repositioning the bones.  There are two techniques

a) I believe more surgeons are using a technique to cut the bone at the site of the bony fusion (the           synostosis).  This works but, in my opinion, has a few challenges.  

        It requires metal pins for approximately 6 weeks while the bone is healing.  Pins can                             sometimes cause problems.  Pins are typically removed in the office but occasionally in the                operating room.

        Like every surgery, there can be complications. 

b) A two- stage procedure called osteoclasis.  I like and use this procedure with younger kids.  Each stage is straightforward.  In the first stage, the bones are cut but not moved.  This limits the nature of the surgery and the risks.  In the second stage, the bones are rotated to the desired position and casted.  Healing almost always occurs by 6 weeks.  The negative of this surgery is the fact that it is 2 stages but there are many advantages for the right child and the right family. 

Here is a great example.  The four x-rays capture the deformity and the joining of the bones (again, the formal name is synostosis) near the elbow.  

Forearm synostosis.  Arrow points to the bony joining bw radius and ulna.

Forearm synostosis.  Arrow points to the bony joining bw radius and ulna.

This young patient was treated with a two- stage osteoclasis procedure.  Below are a few pictures marking the incisions and the initial x-rays for the first stage.  The incisions are quite small (< 1 inch).  

Marked (two dots) planned incision for osteoclasis procedure in which the radius bone is cut

Marked (two dots) planned incision for osteoclasis procedure in which the ulna bone is cut

After cutting the radius and ulna for forearm synostosis

After cutting the radius and ulna for forearm synostosis

There is not much to share after the second stage (rotation of forearm to the desired position).  You might wonder- why not do all in one stage?  This is a great question with two answers.  Delaying the rotation decreases complications and helps to maintain the new position b/c the bone are 'sticky' as they start to heal.  That is why no metal (pins) are required.

Thanks for reading,

Charles A. Goldfarb, MD              


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