In 2013, Chromosome 17q21.31 Microdeletion Syndrome was given a name. It is now officially called Koolen-deVries Syndrome and we refer to our kids as the “kool kids”.
Chromosome 17q21.31 micro deletion syndrome {now called Koolen-deVries Syndrome} is a very rare genetic condition in which a tiny piece is missing from one of the 46 chromosomes, in this case the 17th chromosome.
This syndrome is a multi-system disorder characterized by developmental delay, intellectual disability, muscle weakness (hypotonia), epilepsy, distinctive facial features and congenital malformations of the heart, urogenital tract and the central nervous system. Not all individuals with KdVS have all these features, i.e., the clinical spectrum of the condition is wide.
Symptoms of 17q21.31 are that some babies are born small and light for dates. In the early days, when feeding is difficult, growth may falter but it usually normalises. In time, some children catch up, but others remain short compared with other family members and a few are extremely short.
Young babies are very floppy, have difficulty feeding, often require tube feeding, babies will smile, hold their head up, sit, stand, move and walk and talk late and will have difficulty making the sounds of speech, and will always require support with learning.
Children and adults look more like others with 17q21.31 than like other members of their family. Some children have silvery hair but this usually darkens with age. Eyes are most typically blue. Children often have a tubular or pear-shaped nose with a bulbous tip that becomes more obvious with age, an open mouth and protruding tongue.
Other common features include a high forehead; upslanting eyes, sometimes with tiny skinfolds at the inner corners; and large ears. In time, the face may lengthen and features lose their delicacy.
Birth or development defects
When people have been described with a particular disorder, some conditions that may be typical for the disorder may not be listed. Conversely, conditions may be listed that are not typical. Most children and adults have no important birth defects. Boys are commonly born with undescended testicles. One baby in three has an anomaly of the kidneys or urinary system. Around a quarter are born with a hole in the heart, which may resolve naturally or be corrected by surgery. One baby in four is born with clicky or dislocated hips, requiring stabilisation to improve the development of the hip joint. Brain scans in more than one in three showed wide ventricles (the fluid-filled spaces in the brain). Three babies had a split in the roof of the mouth and one in four a hollowed chest. Two babies were born with craniosynostosis (premature fusion of some of the bones of the skull) and one had her skull reshaped surgically. The same child has glycogen storage disease type O, a very rare liver disorder.
Unusual features of the hands and feet are common in people with this chromosome disorder. Most are cosmetic - such as having long, slender fingers or slender lower limbs - but talipes (club foot) has occurred, where the feet need repositioning to make walking easier. A teenager and an adult each developed hallux valgus where the big toe tilts towards the smaller toes and a bony ‘bunion’ appears on the inside of the foot. Wearing comfortable wide-fitting shoes and padding the bony lump may deal with any discomfort. If that is not sufficient, a chiropodist can advise and if necessary, the joint can be corrected. These two individuals also developed pes cavus (an excessively high arch). Cavus feet tend to be stiffer than normal and may not take pressure as well as normal feet, aching if weightbearing for a while. Basic foot care is important and it may be hard to find well-fitting shoes. If necessary, an orthopaedic foot surgeon can advise about surgical correction. A further boy had flat and painful feet and had successful surgery (subtalar arthrodesis) to fuse bones in the heel. As a teenager he walks independently and wears shaped insoles to relieve pain.
Medical concerns
Children and adults are generally healthy. Seizures occur in around half but these usually seem to be easy to control with medication and some children outgrow them. A squint (strabismus) and long sight are also common and at least one child had cataracts removed from both eyes. Hearing appears usually to be normal, but a slight hearing loss in both ears was found in one child and a mild-to-moderate conductive and sensory loss in another, a low immune system is recorded too.
Behavior
Parents report that their children are friendly, amiable, co-operative and like to make others laugh. Some have a tendency to develop ‘fixations’ on items like foods or favorite films. Some children also have sensory issues.
Emily and Dr. David Koolen - July 2013
Emily’s letter from Genetics …..
Here is the letter written after Emily’s genetic appointment at The Children’s Hospital of Philadelphia, written on June 20, 2008.
The patient: Emily Egner was seen today due to a history of seizures, hypotonia, developmental delay and now a microdeletion at 17q21.31 seen on Comparative Genomic Hybridization.
My findings include the above, as well as: HC at the 75%, Length at the 25%, interpupillary distance 60%, wide spaced nipples, long philtrum, anteverted nares, bulbous nasal tip. She has a history of congenital hip displasia, and seizures associated with fevers. She does not walk at this time of 21 months and has few words, not used discrimantely.
Comment: The 17q21.31 is a newly described microdeletion syndrome, which is present de novo in this child (parents studies were normal). All of the children previously described were hypotonic with delay in motor milestones; some walked at 24 months, 21 months, 19 months and others not until after age 3. There was one child with a single seizure and another with a petit mal seizure. There is one child reported with congenital hip displasia. There were children with wide ventricles. Because one of the children had cataracts and one had mild macular pigment abnormality, I have recommended that the patient see opthomology. Although there are few patients reported with this at this time, those that were older were functioning at the moderately retarted range requiring special schooling.
This is a newly found microdeletion syndrome, so there is still very little information out there. As more cases are found, more info will certainly be learned.
Elaine H. Zackai, MD Director Clinical Genetics Center The Children’s Hospital of Philadelphia
What is Hypotonia?
Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child’s development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy to help the person compensate for the neuromuscular disability.
Muscle tone vs. muscle strength
The low muscle tone associated with hypotonia must not be confused with low muscle strength. In body building, good muscle tone is equated with good physical condition, with taut muscles, and a lean appearance, whereas an out-of-shape, overweight individual with fleshy muscles is said to have “poor tone.” Neurologically, however, muscle tone cannot be changed under voluntary control, regardless of exercise and diet.
In an article by Diane E Gagnon, M.Ed., PT, she explains “True muscle tone is the inherent ability of the muscle to respond to a stretch. For example, if you quickly straighten the flexed elbow of an unsuspecting child with normal tone, the biceps will quickly contract in response (automatic protection against possible injury). When the perceived danger has passed, which the brain figures out really quickly once the stimulus is removed, the muscle then relaxes, and returns to its normal resting state. “…The child with low tone has muscles that are slow to initiate a muscle contraction, contract very slowly in response to a stimulus, and cannot maintain a contraction for as long as his ‘normal’ peers. Because these low-toned muscles do not fully contract before they again relax (muscle accommodates to the stimulus and so shuts down again), they remain loose and very stretchy, never realising their full potential of maintaining a muscle contraction over time. ”
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