The Warburg Micro Syndrome Series 2016 – Muscles and Joints

WMS Muscles and Joints

 

Children with Warburg Micro Syndrome commonly have hypotonia, progressive joint contractures, and spastic diplegia with increasing spasticity that may eventually lead to spastic quadriplegia in later years.  (Graham et al., 2004, Morris-Rosendahl et al., 2010, Handley et al. 2013)

In understandable language, this means that babies with WMS typically have low muscle tone. They may feel floppier than other babies of the same age. When lifting them forward to a sitting position with their arms, they may have some head lag. While at rest, their arms and legs may fall to their sides. Not all babies have hypotonia. They may also have mixed tone. In this case, their arms or legs may feel stiffer than their trunk. In a resting position, instead of falling to the sides, their legs may be straight and crossed. Their arms may be held in a bent position. Think of low muscle tone like a wet noodle. High muscle tone is the uncooked version.

Joint (or muscle) contractures result when muscles become too tight and shorten. When this happens, it  may be difficult to straighten that joint.

Spastic diplegia is when the muscles of the lower extremities exhibit tightness and high tone. Spastic quadriplegia is involvement of the upper extremities as well.

MaryEllen had very low muscle tone as an infant. She was very floppy and had difficulty with head control. It always seemed as if her head was too heavy for her neck muscles to handle. When she was at rest, her legs fell to the side and her arms were bent.

MaryEllen as an infant.

MaryEllen’s head control improved as she got older, but she preferred the frog-leg position for many years. At age 7, her left hip started to cause her great pain and it was discovered that it was subluxated. (The top of the femur, the ball, was not positioned in the hip joint completely.) It was recommended that she have a varus derotation osteotomy. This surgery entails cutting the top of the femur and angling it into the socket part of the hip. The femur is stabilized with screws.

Varus derotation osteotomy, before and after. (Not MaryEllen)

She was placed in a spica cast for six weeks. For MaryEllen, recovery was tough. While casted, she had frequent spasming of her leg muscles that caused her a great deal of pain. (Most children have an uncomplicated recovery.)

Spica cast
Spica cast

MaryEllen’s right hip became subluxated shortly after the left. We opted not to have this surgery done. It was hard to see MaryEllen so uncomfortable throughout the healing process of her left leg that we couldn’t do it. It was strongly suggested that we have the surgery done because as MaryEllen grew older, she would most likely have severe and unrelenting pain. It was a difficult decision. In those days, there were no other WMS children and families. We were told that her life expectancy was very short. In our hearts, we felt that comfort was more important than possible discomfort as an adult.

By age ten and until now, MaryEllen has experienced increasing tone in her extremities. Her trunk tone remains low. She has contractures in her knees, wrists, and fingers.

 

Young MaryEllen. Even though she held her fingers in a closed position, they were easily opened and functional.

 

Older MaryEllen
MaryEllen’s arms and fingers have become tighter. She is no longer able to open her hands. Her knees do not straighten.

Due to MaryEllen’s very low trunk tone, she has severe scoliosis (curvature) and kyphosis (hunchback) of her spine. It was evident by age 15, and it was highly suggested that she wear a scoliosis brace. This is a type of rigid stabilization to prevent further curvature. It can be very restrictive for breathing. MaryEllen already was a shallow breather. Her pulmonary doctor thought that it was not a good idea for MaryEllen. It was also suggested that she have spinal fusion surgery to straighten the spine. Again, we opted for comfort for MaryEllen. There were still no other WMS families that we knew of and we were not certain she would live until adulthood.

That’s where we are now. She does not exhibit any hip or spine pain that we know of. She breathes with the use of a ventilator for most hours of the day but does very well without it. Her pulse oximetry readings (off the vent) are above 95 on room air and her end tidal CO2 readings are in the low to mid 40s. This is very good!

 

Kevin was different from MaryEllen. Although he had low trunk tone, his legs and arms were much tighter.

Even at birth, you can see Kevin's high tone in his arms.
Even at birth, you can see Kevin’s high tone in his arms.

By four years old, Kevin’s lower extremities were so tight that it made dressing difficult. His legs were always in a crossed position. Carrying him was akin to carrying a board. He was the exact opposite of MaryEllen! His hips were already subluxated.  Kevin underwent a bilateral multiple adductor tenotomy (to make it easier to open and close his legs) as was recommended by his orthopedist. This immediately corrected Kevin’s dressing difficulties.He healed quickly but his hips remained subluxated. As with MaryEllen, we opted not to do (osteotomy) hip surgery.

Kevin's hips. Left and right
Kevin’s hips. Left and right (2013)

Kevin does not have contractures like MaryEllen. He can straighten his knees. His fingers are in a closed position at rest but they are still easily manipulated into an open position. He does have wrist contractures. Both Maryellen and Kevin wore wrist splints from age five until their late teens. They still developed wrist contractures so we opted to discontinue their use. They hated being constrained in a brace and all the years of use did not improve function or comfort.

 

Younger Kevin.
Younger Kevin.

 

IMG_6382
Older Kevin.

Kevin also has severe scoliosis and kyphosis. We were offered and also refused the spine surgery for him. He also has no hip or spine pain that we know of.  Like his sister, Kevin spends time off the vent every day and while off, his pulse oximetry and end tidal CO2 numbers remain good.

Kevin’s spine x-ray and Kevin sitting. You can see his extremely low trunk tone.

MaryEllen and Kevin have switched places. MaryEllen was floppy (hypotonic) as an infant and became tighter (hypertonic) through the years and Kevin was tight and became more hypotonic as he got older.

Kevin and MaryEllen receive physical therapy and occupational therapy twice weekly.  Passive range of motion to all extremities is done to help them move their muscles to help prevent more contractures. PT and OT have been a part of their lives since they were infants.

All children with Warburg Micro Syndrome are not the same. Even within our family, both kids are very different. Your child will be different as well.

 

For more information about Warburg Micro Syndrome as it relates to MaryEllen and Kevin, please see The Warburg Micro Syndrome Series 2016.

Graham, J. M., Jr., Hennekam, R., Dobyns, W. B., Roeder, E., Busch, D. MICRO syndrome: an entity distinct from COFS syndrome. Am. J. Med. Genet. 128A: 235-245, 2004.
Handley, M. T., Morris-Rosendahl, D. J., Brown, S., Macdonald, F., Hardy, C., Bem, D., Carpanini, S. M., Borck, G., Martorell, L., Izzi, C., Faravelli, F., Accorsi, P., and 23 others. Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in Warburg Micro syndrome and Martsolf syndrome. Hum. Mutat. 34: 686-696, 2013.
Morris-Rosendahl, D. J., Segel, R., Born, A. P., Conrad, C., Loeys, B., Brooks, S. S., Muller, L., Zeschnigk, C., Botti, C., Rabinowitz, R., Uyanik, G., Crocq, M.-A., Kraus, U., Degen, I., Faes, F. New RAB3GAP1 mutations in patients with Warburg Micro syndrome from different ethnic backgrounds and a possible founder effect in the Danish. Europ. J. Hum. Genet. 18: 1100-1106, 2010.

If you have any questions about anything related to muscles and joints in Warburg Micro Syndrome, please leave a comment, and I will be happy to answer.

 

 

 

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