How to Care for Cornelia de Lange Syndrome (CdLS) Patient
Cornelia de Lange Syndrome (CdLS) patients can face several medical complications. For those who have been diagnosed and managed early, the outlook is good.
The earlier the treatment, the better. However, most of the available treatments for this syndrome are not specific but symptomatic because of the multiple developmental defects associated. This is why treatment may require treatment from different medical disciplines.
Optimizing the therapy results is a combination of parents’ and physicians’ efforts to early diagnose the disease and provide the appropriate intervention.
Below is a list of challenges faced by patients with CDLS and the most common approaches to overcome such problems.
Limb deformities and malformations
Orthopedic surgery can be used to correct defects in bones or joints that cause limb deformity.
Motor disorders, retardation in growth
The most common solution is hearing aids, but sometimes more specialized methods are used.
Speech retardation and deficits
Development of alternative forms of communication such as sign language and picture exchange communication systems.
Depression, stress, anxiety
Emotional support, psychological care, and if necessary, pharmacological treatment.
Antiepileptics and other pharmacotherapy
Pediatric dentistry surgery recovery
Behavioral therapy and parental support
How to Spot Symptoms of CdLS Early On
The first step of treatment for a child with CdLS is a complete diagnosis. A detailed description of symptoms must be obtained to determine the best course of action.
In addition, since the syndrome covers all other types of disease, early diagnosis will help caregivers know the stage at which to engage, and which therapy should be given priority.
Early diagnosis allows caregivers to provide targeted treatment options that may minimize CdLS patient symptoms and improve their chances of survival.
Possible methods to diagnose a patient with CdLS include:
- Prenatal diagnosis
There are several “red flags” that can suggest a diagnosis of CdLS before birth. This includes a history of an earlier child with CdLS or genetic changes known to be associated with CdLS.
Another sign may be no family history of CdLS, but an ultrasound shows features suggestive of CdLS.
Some of the fetal features that have been associated with CdLS include:
- Abnormal facial profile
- Intrauterine growth restriction (IUGR)
- Prenatal limb differences
- Cardiac malformation
- Clinical Diagnosis
The clinical diagnosis of CDLS is made by considering the clinical symptoms. A detailed physical examination reveals craniofacial characteristics, growth failure, developmental disability, limb malformations, and hirsutism. However, laboratory diagnostic studies are necessary to confirm the clinical diagnosis of CdLS
The clinical evaluation of children with characteristics of the CdLS spectrum includes detailed family history, visual examination, complete ophthalmic and neurological exams, and neurodevelopmental assessment.
- Laboratory Diagnosis
Periodic tests, including blood counts and liver and kidney tests, help pinpoint and treat potential health problems that can arise in children and adults with de Lange syndrome. These tests are recommended for the first year of life.
A radiographic examination will also help doctors identify abnormalities in a patient’s limbs and skull. However, a diagnosis of CdLS can be made only after other limb malformations that are not specific to the syndrome have been ruled out.
- Genetic Testing
There are genetic tests available to identify changes in any of the genes associated with the CdLS spectrum. A clinical geneticist can help parents understand how to interpret the results and if needed have a diagnostic test.
Genetic testing can be done before, during, or after a pregnancy.
i. Prenatal Genetic Test: Prenatal genetic testing can be carried out using DNA from samples of cells obtained during routine prenatal ultrasound or amniocentesis. Alternatively, chorionic villus sampling (CVS), which involves extracting tissue from the placenta. Genetic testing can identify changes in any of the seven genes associated with CdLS.
ii. Postnatal Genetic Test: For patients with clinical features consistent with CdLS, the first-line diagnostic test to check for mutations in known CdLS -causing genes includes screening for CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21, BRD4, HDAC8, and ANKRD11) by next-generation sequencing. The popular genetic testing method includes Sanger sequencing, Panel sequencing, and Mosaicism testing.
Symptoms and expert clinical diagnosis may be enough to identify the syndrome without genetic testing. This Diagnostic Criteria Checklist can assist in diagnosing the syndrome.
Medical Care for CdLS Patients
CdLS is a multi-symptomatic condition, which means that people with this condition will experience more than one symptom. People with CdLS tend to be more susceptible to eye problems, stomach/ intestinal issues, genital problems, and limb abnormalities.
Therefore, Doctors and Pediatricians often work together to assess the patient, then provide individualized therapy for each symptom.
The syndrome may have different effects on the patient at different stages in their life. Caregivers respond by providing care individual therapy from childhood to adulthood.
Individual therapy for CdLS patients bridges different professions, such as physical therapy, pediatricians, surgeons, and more.
Pediatric Care: Care between 1-8 years
CdLS is usually diagnosed in early childhood by an experienced pediatrician or clinical geneticist. An involved doctor (pediatrician) also plays a crucial role in the care of the child.
Once the accurate diagnosis is done, the next step involves looking for early-stage abnormalities and deformities. Sometimes, this comes by close examination and monitoring. Other medical interventions may include speech therapy, vaccinations, and more
Here are ways to care for CdLS patients in their childhood:
- Regular evaluations and immunization
Clinical evaluation of patients with suspected Cornelia de Lange syndrome should include cardiology examination and renal ultrasound to evaluate the heart and kidneys, respectively.
To manage the symptoms of attention deficit disorder, an initial assessment should include a hearing evaluation, an evaluation for gastroesophageal reflux disease, and a test of electrical activity in the brain (electroencephalogram or EEG).
Similarly, every child with Cornelia de Lange syndrome should receive age-appropriate vaccinations as recommended by the U.S. Centers for Disease Control and Prevention (CDC). The goal is to prevent serious complications such as pneumonia and meningitis.
- Physical, occupational, and speech therapy
Physical therapy programs for CdLS patients should be designed to address hypotonia and global developmental delay. Majorly, it consists of proprioceptive exercise, gross motor skills training, and functional activities.
Since it’s easier for children with CdLS to acquire visual memory, the use of visual-based programs over verbal programs is more beneficial to them.
People remember images more than words. A perceptual organization should be emphasized by teachers. This is because stimulating the children’s tactile senses while introducing new material makes them remember it better. If kids do an activity with their hands while they are learning, they will remember more.
- Monitor growth via CdLS-specific growth chartsIt’s important not to push things with your child. Children with Cornelia De Lange Syndrome are statistically shorter and smaller than their peers. Certain high-calorie formulas treatment is often suggested, but CdLS kids seem to grow at their own pace with a high metabolic rate.
CdLS patients usually have normal growth hormone levels. But in cases when a growth profile shows a lower concentration, growth hormone therapy can be administered to help with growth. Caregivers should weigh the benefits of taking growth hormone supplements against the burden of daily injections.
In addition, growth charts are available that are specific to individuals with CdLS. These charts should be used to monitor the growth of every child with CdLS.
Female height chart for CdLS patients. Source: Growth Charts
Male height chart for CdLS patients. Source: Growth Charts
Check here for other height and weight charts (female and male) of other age range
- Audiology testing
Audiology testing enables caregivers to keep close track of CdLS patients’ hearing development. This testing is necessary because children with Cornelia de Lange syndrome are predisposed to certain types of ear infections that can lead to permanent hearing loss. An audiology test should be performed every two to three years for children diagnosed with CDLS at birth.
- Feeding, Dental Evaluation
Individuals with the classical form of CDLS have a variety of feeding difficulties because of their respiratory involvement. The most effective method of feeding is oral, but several methods may be necessary to improve tolerance to oral intake. These include propping or sitting upright for feedings and/or providing high-calorie medical nutritional supplement drinks together with feedings.
Cleft lip and palate may cause feeding difficulties that are even further worsened by dental issues like gaps, teeth with cavities, misaligned jaws, teeth grinding, and more. It is important to consult a dentist regularly to prevent early plaque buildup.
It is important to ensure regular dental evaluations to help prevent further damage and the spread of existing dental damage.
Late Childhood (eight years – puberty)
Most individuals diagnosed with CDLS can pass into adulthood due to advances in medical care, particularly within the first year of life. Consequently, the core focus of care in the late childhood stage is to strengthen individuals by providing them with assistance in all stages of their development. Some of the medical intervention at this stage includes the following:
- Orthopedic care: At this stage, the patient may develop scoliosis, hip complications, or joint contractures. Orthopedic intervention is needed to correct some of the implications.
- Behavioral assessment: Behavioral therapy early in life is effective in managing symptoms that may include mood swings, inappropriate behavior, anger issues, and hand flapping. Family support, including close monitoring by parents and teachers, is essential.
- Any sign of potential volvulus: Volvulus (or torsion) is a complication of the de Lange syndrome. It is where the small intestine twists around itself, causing blockages and stoppages in the small intestines. Any sudden acute abdominal pain could be a sign of something seriously wrong and should merit an immediate visit to the emergency room.
Adults with CdLS often become overweight due to a diet high in carbohydrates and sugar, and physical activity that is limited. They may also have a higher risk of developing type-2 diabetes.
Ideally, their diet should be low in refined sugar, high in fruit and vegetables, with the amount of fat based on both their taste and medical advice.
Other adulthood interventions for an adult with CdLS includes:
- Ongoing developmental services. Since people with CdLS have a wide range of needs, developing a plan for life after high school is often a group effort. A variety of options need to be discussed and considered, including job training, assistive devices, and higher education. These discussions may help people with CdLS find the right fit for their skills and abilities.
- Pap Smear: Women with CdLS should be examined with a Pap smear test, which can detect cervical cancer and precancerous changes in the cervix, every three years while sexually active and throughout their lives.
- Behavioral assessment: The CdLS patient behavioral assessment includes tests and therapy for evaluation of self-injurious behavior (SIB), attention deficit disorder (ADD), and autism spectrum disorder (ASD).
- Repetitive behavior: Repetitive behavior is a common feature of CdLS. These repetitive behaviors are typically found in children, but they may present in adults as well. Parents and carers should be aware that due to the nature of Cornelia de Lange Syndrome, not all repetitive behavior is abnormal or an indication that treatment is needed.
Follow-up is Essential
All patients with CdLS should be followed up by a pediatrician or clinical geneticist experienced in CdLS at least annually during infancy and early childhood and may be followed up less frequently during adolescence and adulthood if they are medically stable. In case of problems, the schedule may need to be adapted but may follow a similar pattern.
- What is Cornelia de Lange Syndrome?
CdLS is a congenital birth defect caused by defects of chromosome-12. A person with the syndrome has an altered brain development, abnormal facial features, and skeletal abnormalities.
- How will the syndrome affect life expectancy?
A person with Cornelia de Lange syndrome may live into early adulthood or middle age. This often depends on the severity of the symptoms, the types of associated syndromes, and whether or not there are any complications.
- Can individuals with CdLS have children?
Some women with Cornelia de Lange syndrome have given birth, however, the exact rate of fertility is unknown.
- Can CdLS patients develop cancer?
There is currently no evidence that young individuals with CdLS are at an increased risk of developing cancer. However, middle-aged and older individuals with CdLS may be at an increased risk of developing cancer of the esophagus.