Chromosome 2p Duplication Syndrome

What Is Chromosome 2p Duplication Syndrome?

Chromosome 2p duplication syndrome is also known as 2p duplication syndrome and trisomy 2p syndrome. It is a rare hereditary condition that is caused due to the presence of an extra copy of chromosome 2 in the body's cells. In 2p duplication syndrome, the duplication (extra copies) takes place on the short arm of one of the chromosomes 2, hence, the name. In the majority of cases, the duplication happens due to random mutations (de novo), and in a few cases, it is inherited from parents.

The associated signs and symptoms depend on the amount of genetic material duplicated, the number of genes affected, and the function of the affected genes. Commonly seen symptoms are developmental delays, intellectual disability, behavioral problems, and skeletal malformations. The condition can be diagnosed with genetic testing; treatment primarily involves managing the symptoms with the help of a multidisciplinary team. Many individuals cope well with early intervention and adequate supportive care.

What Causes 2p Duplication Syndrome?

Humans have 46 chromosomes (divided into 23 pairs) in each cell; each half of the pair is inherited from one parent. Chromosome 2 is the second largest human chromosome; it has 243 million DNA (deoxyribonucleic acid) building blocks that line up to form around 1300 genes. These genes provide instructions to make various proteins that are responsible for different functions in the body.

During fertilization, the genetic material from the maternal and paternal sides divides (replicates) and rearranges itself to form the resultant egg, which then undergoes repeated cell division to form a human. Occasionally, mutations (alterations) occur during the replication and rearrangement process. Mutations are often random, but if the mutation results in extra copies of the genetic material, then the condition is known as duplication, and when this happens in the short arm of chromosome 2, it is known as 2p duplication syndrome.

What Are the Symptoms of 2p Duplication Syndrome?

The commonly seen signs and symptoms are-

• Behavioral problems such as mood swings and aggressiveness.

• Congenital (present at birth) heart conditions are seen in nearly 50 percent of the cases. Some of the commonly seen defects are the atrial septal defect (ASD; a defect in the septum that separates the upper chambers of the heart), the ventral septal defect (VSD; a defect in the septum that separates the lower chambers of the heart), coarctation of the aorta (abnormally narrow aorta), persistent ductus arteriosus (PDA; an abnormal, persistent fetal communication between the pulmonary artery and the descending aorta), and atrioventricular canal defect (a congenital condition that affects the valves of the heart). All of these conditions have chest pain, dizziness, shortness of breath, fainting, tiredness, and palpitations in common.

• Distinctive facial features are typical for 2p duplication syndrome. Some of them are- a large and prominent forehead, low nasal bridge, wide-spaced eyes, low-set, backward-slanted ears, small triangular mouth, small chin with a lower jaw, etc.

• Abnormal hands and legs.

• Cleft palate (an opening or split in the roof of the mouth).

• Vision problems are seen in nearly 80 percent of the affected children; this includes strabismus (a condition in which both eyes do not line up in the same direction), underdeveloped eyes, obstruction of the tear ducts, and refractive errors.

• Hypotonia (low muscle tone) leads to floppiness in babies.

• Short stature indicates a deficiency in growth hormone.

• Gastroesophageal reflux disease and associated feeding difficulties.

• Constipation.

• Developmental delays include delays in milestones like rolling, sitting, standing, and walking.

• Cognitive impairment and intellectual disability.

• Speech and language difficulties.

• Sleep disturbances like sleep apnea.

• Pulmonary defects like the presence of one lung and small-sized lungs.

• Genital abnormalities like hypospadias, shawl scrotum, and undescended testicles.

• Gastrointestinal abnormalities like Merkel’s diverticulum and intestinal malrotation.

• Increased predisposition to hernias like inguinal hernial, diaphragmatic hernia, and umbilical hernia.

• Dermatological manifestations like eczema.

• Dental problems like malocclusion (malalignment).

It is important to note that not individuals with 2p duplication syndrome will not have every single symptom mentioned above; the severity of the symptoms depends on the extent of the duplication.

How Is Chromosome 2p Duplication Syndrome Diagnosed?

Given the condition's rarity, the healthcare provider must have a high index of suspicion to consider chromosome 2p duplication syndrome as part of the differential diagnosis. Although genetic testing helps with the final diagnosis, a few evaluations and assessments must be performed prior; these help with the initial diagnosis and in understanding the extent of the mutation. Some of them are-

1. Complete physical examination, along with the individual and family's medical history.

2. Medical evaluation of different body systems, like the heart, brain, genitals, kidney, vision, musculoskeletal, hearing, etc.

3. Speech and language assessment.

4. Behavioral evaluation.

5. A comprehensive metabolic panel (CMP) is used to evaluate the body's kidney and liver function.

6. In cases of pregnancy, if the maternal or paternal side has 2p duplication syndrome, and alpha-fetoprotein levels, an abdominal ultrasound can be used to determine the condition ahead of the birth.

7. Genetic testing is the gold standard for diagnosing chromosomal mutations; some of the frequently used techniques to diagnose 2p duplication syndrome are fluorescence in-situ hybridization (FISH) testing, DNA sequencing, and array comparative genomic hybridization (array-CGH).

How Is Chromosome 2p Duplication Syndrome Treated?

Treatment is focused on providing relief from the symptoms; this is done under the supervision of a multidisciplinary team comprising cardiologists, occupational therapists, ophthalmologists, endocrinologists, behavioral therapists, etc. Individuals with mild symptoms will require periodic monitoring without significant medical intervention.

Some of the treatment measures frequently used are-

• Speech and language therapy.

• Surgical correction for septal defects in patients with congenital heart conditions.

• Physical therapy for hypotonia and weakened muscles.

• Occupational therapy.

• Severe gastroesophageal reflux in children can be treated with fundoplication. During this surgical procedure, the top of the stomach is folded and sewn to the lower esophageal sphincter.

• Use of visual and hearing aids in individuals with vision and hearing defects.

• Motor skills can be improved with swimming, light exercise, and adaptive activities.

• Patients with feeding difficulties can be improved with the help of specialized nutrition, vitamin and nutrition supplements, and feeding tubes (in extreme cases).

• Sleep apnea can be addressed with medication or with a continuous positive airway pressure (CPAP) machine.

• Dermatological manifestations can be addressed with topical emollients and corticosteroids.

• Psychotherapy, disciplining techniques, and behavior modification will help children with aggression and behavioral abnormalities.

Even with some of the management techniques mentioned above, complications like failure to thrive, severe intellectual deficiency, inappropriate and violent behavior, etc., can be seen occasionally.

Genetic counseling plays an important role in handling these complications; it is defined as providing information about the condition to the individual and their family members about the mode of inheritance and implications of the conditions. This helps to manage and prevent complications in genetically inherited conditions.

Conclusion

Individuals with 2p duplication syndrome have an extra copy of chromosome 2 in their genetic makeup. The condition manifests at an early age and has a systemic presence, but the most commonly observed symptoms are neurological in nature. The developmental pediatrician plays an essential role in diagnosing and managing the conditions. The prognosis is often good with early intervention.