Makenna's Chromosome 4q Deletion

Chromosome 4q Deletion Syndrome is a rare chromosomal disorder in which there is deletion of a portion of the 4th chromosome. Deletions may be in the middle of the chromosome arm (“interstitial”) or at the end “terminal”) and have varying effects. There are enough common features for children with deletions anywhere along the range that it has been called a syndrome, but as with most rare genetic issues, the differences between children can be tremendous. Visually there are commonalities between kids, much as with Down Syndrome, in this case, the most distinctive visual features include short limbs, a high “frontal bossing” on the forehead, large head, wide set eyes, low set ears, thin upper lip and short, high nose. This gives children a “babyish” look for longer, which can be compounded by motor issues.

Causes

Most 4 q deletions are happening randomly near the time of first cell division after conception. A small percentage of cases are inherited, and for reasons not fully understood, normally functioning parents may have severely affected children, either because they are lacking a translocated piece, or because of environmental issues during gestation or early childhood.

Disorder Symptoms

There are many symptoms and characteristics that affect people with Chromosome 4q Deletion Syndrome.

Low muscle tone is very common, as are gastrointestinal reflux, hearing issues, vision issues, large head, small feet, turned in pinkies, flat bridge of nose, slight epicanthic folds, low set rotated ears, “funny” feet (they bend in a strange place or have overlapping toes or are particularly flat or rocker-bottom). Short limbs compared to torso size are also not unusual, short wide hands and feet are also common.

Hands and feet may be shorter and wider than normal, "tiny feet" are very common. Toes may bend at funny places (the second joint bending down for example) or overlap.

Reflux and coordination issues may make sucking and eating difficult, and even fully nourished children may not grow very well on a normal diet. Breastfeeding children with 4q deletions is very challenging but has been done, bottlefeeding is not generally much easier.

Heart defects appear to be very dependent on the specific genes involved in the deletion. For example, most children with (del)4q21.1-21.3 do not have heart issues.

Large head, craniostenosis, wide set eyes, small facial features, distinctive nose (wide, flat, high bridge), thin lips, small or receding chin.

Low muscle tone and poor muscle control due to an error in signaling between the brain and the muscle can contribute to global delays.
Most often dysmorphic features will prompt a pediatrician or other doctor to order genetic testing. Some children are diagnosed at or near birth, others are diagnosed years later. Most children with 4qdeletion look “mostly” normal to the casual observer, the markers are a little subtle. It is not possible to determine by looking at someone whether they have 4q deletion syndrome, but visual appearance may be
just different enough to prompt doctors to order tests.Diagnosis
Diagnostic Tests

Diagnosis is done with a blood test. A karyotyping test generally finds the gross chromosome deletion, other testing will explain specific breakpoints and determine whether or not the deletion was inherited or a new mutation.

Disorder Treatments

Most treatments are symptomatic, but it is important that all children with 4q deletion syndrome have testing done for metabolic abnormalities. Many children (even those without a frank deficiency) will benefit from use of Coenzyme Q10. Other treatments that have been helpful include Carnitine and R-Lipoic-Acid (for any child with “metabolic symptoms” such as low tone).

Multivitamin supplementation may be helpful to many.

Some children with 4q deletions show signs of reflux, treatment of that may help growth issues. CoQ10 seems to help both reflux and growth issues in some children.

Some children also show symptoms of problems with citric acid, it is suspected that this may be due to problems with the Kreb’s Cycle. Restricted citric acid diets have been helpful for some children.
Prognosis

In general, delays are endemic, in many children, most even, receptive language is better than expressive, and children may never have much functional expressive language. Early sign language and speech therapy, plus alternative communication methods may mitigate this somewhat, but oral motor skill issues combined with a fundamentally different brain process mean that language is a challenge for most children, and “lost language” even more of a problem. Some children may develop vocabulary and lose it, often learning and losing the same words over and over again.

Prognosis is highly variable. There are kids who are just a little delayed, but go to a mainstream school program and learn to talk and walk just a little behind schedule. More typical seems to be to crawl sometime after the first year, walk sometime between age 2 and age 5. Some children do not sit up, crawl or walk until much older.

Autism is often diagnosed in kids with 4q deletion, there is new research indicating there may be a gene that causes autism in girls on the long arm of the fourth chromosome. Autistic symptoms may be atypical, but are very common.

Most children with 4q deletions will require lifelong help and support.

All that said, they seem to be particularly charming and engaging children, all behavior issues aside.