What are the other Names for this Condition? (Also known as/Synonyms)

• Deletion 2p Syndrome
• Monosomy 2p Syndrome
• Partial Monosomy 2p Syndrome

What is Chromosome 2p Deletion Syndrome? (Definition/Background Information)

• Chromosome 2p Deletion Syndrome is a rare chromosomal disorder that develops when there is missing genetic material on chromosome 2 (on short arm p) leading to a set of associated signs and symptoms. These may be mild or severe, depending on several factors such as the amount of genetic material lost, the number of genes affected, and the function of the affected genes
• The condition affects newborn children (congenital manifestation). It can result in developmental delays, mental health retardation, seizures, and abnormal facial features. 2p Deletion Syndrome may present complications such as malnutrition due to feeding difficulties, delayed achievement of milestones, and reduced quality of life
• This chromosomal anomaly may develop from sporadic mutations (vast majority of cases), or it may be inherited from one’s parents (very rarely). Chromosome 2p Deletion Syndrome may be diagnosed through specialized genetic testing. In some children, the condition may be mild and hence can also remain undiagnosed
• Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of the body systems. The treatment may involve physician experts from several specialties, and can include the use of special education, speech and language therapy, physiotherapy, and surgery for correction of physical defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 2p Deletion Syndrome are able to cope well through adequate treatment and supportive care. Some of the signs and symptoms associated with the condition are known to improve with time

Who gets Chromosome 2p Deletion Syndrome? (Age and Sex Distribution)

• The incidence of Chromosome 2p Deletion Syndrome is about 1 in 12,000 live births among the general population. In the medical literature, less than 50 cases have been reported
• In many cases, individuals with mild signs and symptoms may be undiagnosed in their lifetime. Hence, a true incidence of the disorder may be difficult to estimate
• Chromosome 2p Deletion Syndrome is a congenital disorder and the presentation of symptoms may occur at or following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Chromosome 2p Deletion Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 2p Deletion Syndrome.

• In some individuals, a positive family history may be an important risk factor for 2p Deletion Syndrome
• Currently, no environmental and lifestyle (including dietary) factors have been implicated
• The syndrome is not caused by what the expectant mother does or does not do, either prior to or during pregnancy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chromosome 2p Deletion Syndrome? (Etiology)

Chromosome 2p Deletion Syndrome is caused by deletion of genetic material from the short arm (p) of chromosome 2; the amount of missing chromosome material varies widely from one individual to another resulting in a variable set of signs and symptoms.

• There are two chromosomes numbered 2. Children with 2p Deletion Syndrome typically will have one (chromosome 2) in normal condition, while the other is abnormal. The abnormality is characterized by a loss of chromosomal material
• The type of deletions may be termed proximal (when it is closer to the center of the chromosome), distal (when the deletion is closer to the tip), interstitial (when there are two breakpoints in the chromosome arm), and terminal (when the tip/end of the chromosome is lost). However, when only a tiny portion of the genetic material is missing, it is termed as a microdeletion. The signs and symptoms may vary considerably based on the location of the deletion
• In a few cases, a balanced translocation is observed. In this form of abnormality, a balanced rearrangement of the chromosomes takes place, where the chromosomes exchange (or swap) genetic material such that there is no net loss or gain of genetically important material. Due to this, no significant signs and symptoms are generally noted. Those with balanced translocation can have abnormalities in the development of the egg or sperm, causing the disorder in their offspring
• The involvement of the following genes have been noted in 2p Deletion Syndrome:
  • SIX3 gene - the involvement of which may be responsible for holoprosencephaly
  • MSH2 and MSH6 genes that are involved in DNA repair
  • SNTG2 gene, which is essential for CNS development
  • NRXN1 gene that is important for proper cognitive function
• Most cases of the disorder develop sporadically (de novo) during embryonic development. This means that no deletion of genetic material at 2p is observed in either of the parents. However, in rare cases, Chromosome 2p Deletion Syndrome may be inherited

It is important to note that a child’s development and future is not only influenced by the chromosome material duplicated/deleted and genes involved, but also by other factors such as one’s environment, involvement of other genes, and unique personality.

Additional (general) information on chromosomes, which is helpful in understanding the disorder:

Chromosomes are microscopic thread-like protein structures present in each cell nucleus that carry genetic information in the form of DNA (deoxyribonucleic acid). DNAs are nucleic acids that encodes the genetic information of any organisms; a basic unit of the DNA is termed a gene with a specific set of instructions and a defined function. Each chromosome is “X” shaped with a center, called the centromere, and two short arms (termed p arms) and two long arms (termed q arms).

Humans have 46 chromosomes in the cell nucleus, in 23 pairs, of which one pair is named the sex chromosome. In males, it is designated XY, for chromosome X and chromosome Y; while, in females, it is designated XX, for a pair of chromosome X. The other 22 pairs of chromosomes are numbered chromosome 1 through 22, approximately according to size (with chromosome 1 being the largest; chromosome 21 being the smallest) and are referred to as autosomes or somatic chromosomes. During conception, the embryo inherits one copy of each chromosome from each parent (i.e., mother and father). Any alteration in the chromosome numbers or structure, such as via addition or deletion of chromosomal material, can result in mild to severe genetic abnormalities that may manifest as birth defects, growth delays, and intellectual disabilities.

A chromosome deletion disorder indicates that a certain portion of the chromosomal material is missing, which may be detected through molecular genetic testing. Depending on the nature and amount of material deleted, the manifestation of a set of signs and symptoms are noted.

What are the Signs and Symptoms of Chromosome 2p Deletion Syndrome?

The signs and symptoms of Chromosome 2p Deletion Syndrome may be significantly different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material deleted and the number of genes affected. As a general rule, a small loss of chromosome material generally results in milder signs and symptoms. Conversely, larger deletion of the chromosome material generally results in severe signs and symptoms. It is important to note that exceptions may also occur, where individuals with small amount of chromosomal loss, may have disproportionately severe presentations.

The commonly noted signs and symptoms of Chromosome 2p Deletion Syndrome include:

• Distinctive facial features such as:
  • Small and asymmetrically shaped head
  • Prominent or narrow forehead
  • Large eyes; droopy upper eyelid
  • Prominent nasal bridge; small nostrils
  • Deformed ears
  • High palate
  • Small chin and jaw
• Developmental delays; delays in milestone achievement such as rolling, sitting, crawling, and walking
• Poor fine motor skills
• Intellectual disability
• Behavioral problems such as social awkwardness and temper difficulties
• Speech and communication difficulties
• Low muscle tone (hypotonia) that may result in floppiness
• Feeding difficulties due to swallowing difficulties, vomiting, and gastroesophageal reflux disease (GERD)
• Constipation may be commonly noted in children
• Genital abnormalities that are generally minor and surgically correctable
• Epileptic seizures
• Abnormally-formed hand and feet, particularly the fingers and toes, requiring surgical correction; clubfoot
• Glue ear (fluid build-up in middle ear) causing hearing loss
• Vision defects that include strabismus, nystagmus, and refractory errors
• Heart anomalies may rarely include ventricular septal defect (VSD), atrial septal defect (ASD), and heart murmurs. It can result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others

How is Chromosome 2p Deletion Syndrome Diagnosed?

Children can have varying signs and symptoms. Some children with mild signs and symptoms may go undiagnosed in their lifetimes. Given the rarity of the condition, the healthcare provider should have a high index of suspicion to consider Chromosome 2p Deletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 2p Deletion Syndrome is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms, including evaluation of body systems such as vision, hearing, muscles, heart, kidneys, central nervous system, genitalia, and immune system
• Hearing assessment through various tests including:
  • Otoscopy: Examination using an instrument that allows the physician to look inside the ear
  • Weber test: A test in which a vibrating tuning fork is placed on the midline of the head
  • Rinne test: A test in which a vibrating tuning fork is held next to the ear and then in front of the ear, until the individual no longer hears the sound
  • Audiometric test: Hearing tests that involve listening to different tones
• Eye and vision assessment through:
  • General eye exam
  • Visual acuity test using a special and standardized test chart (Snellen chart)
  • Refraction studies using various instruments
  • Fundoscopic (ophthalmoscopic) examination by an eye specialist, who examines the back part of the eye (or the fundus)
  • Slit-lamp examination
• Laboratory tests, as needed, such as electrolyte levels, serum calcium levels, thyroid function test, kidney function test, urine tests, sex hormone studies, etc.
• Radiological studies of the affected regions, as needed
• Evaluation of heart defects
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Behavioral studies
• Prenatal studies including abdominal ultrasonography
• Specialized genetic testing techniques are often required to confirm the diagnosis. This may include:
  • Fluorescence in situ hybridization (FISH) testing
  • Array comparative genomic hybridization (array-CGH)
  • DNA sequencing

Often, karyotyping of the chromosome is not adequate to diagnose the condition, since individuals with this condition can have normal karyotype chromosomal studies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chromosome 2p Deletion Syndrome?

The complications of Chromosome 2p Deletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Poor growth due to malnutrition caused by weak suckling
• Holoprosencephaly (HPE) or abnormal development of the brain hemispheres causing associated signs and symptoms; this may be mild or moderately severe
• Abnormal spinal curvature causing progressive scoliosis
• Hearing impairment that may cause permanent hearing loss
• Learning disabilities may be severe
• Severe intellectual deficiency
• Developmental abnormalities that can affect day-to-day activities
• Walking difficulties
• Behavior that is violent or deemed inappropriate
• Kidney defects, mainly horseshoe-shaped kidney that may increase one’s risk for recurrent urinary tract infections
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Chromosome 2p Deletion Syndrome Treated?

There is no cure for Chromosome 2p Deletion Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. It also depends on the severity of the signs and symptoms and the body systems affected. Individuals with mild signs and symptoms may require periodic monitoring without significant medical intervention. Often, a multidisciplinary team of specialists including pediatricians, ophthalmologists, otolaryngologists, neurologists, internists, cardiologists, endocrinologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for 2p Deletion Syndrome may involve:

• Use of hearing aids and cochlear implants
• Seizure control using anticonvulsant medication, vitamin supplements, and ketogenic diet: Seizure control is important to ensure that the child’s learning ability is not significantly affected
• Special education: Employing suitable learning strategies via music therapy, visual and tactile books, touch screen computers, etc.
• Speech and language therapy; the use of sign language may be beneficial
• Physiotherapy for weakened muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, and other adapted activities; use of specially-designed toys and daily-used items (such as spoons and cups)
• Use of walking aids including foot orthotics and special footwear
• For feeding difficulties, use of feeding tubes (temporary), medications, feed thickeners, including special diets and nutritional supplements. A surgical procedure named fundoplication may be necessary in some children with severe GERD
• Severe constipation may require dietary changes, including increased intake of fiber and wholegrains, along-with the administration of laxatives
• Surgical correction of physical defects, as assessed by a healthcare expert
• Antibiotic therapy for infections
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time
• Use of padded brace for abnormal spinal curvature and posture management, including surgical correction of severe cases. Also, children may be provided specially designed furniture, such as chairs, tables, and beds, for spine support while sitting and sleeping
• Use of suitable glasses for vision defects
• Surgical correction of genital defects
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy
• Children may need support for basic activities, such as dressing/undressing, and toilet training for many years 

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can Chromosome 2p Deletion Syndrome be Prevented?

Chromosome 2p Deletion Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

In some rare cases, the condition may be familial, meaning they occur within families. In expecting parents with a familial history:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

It is important to note that the chances of both the parents with normal chromosomes having another child with Chromosome 2p Deletion Syndrome is highly unlikely. This may be confirmed via specialized prenatal testing and preimplantation genetic diagnosis (PGD), if needed. Prenatal tests may include chorionic villus sampling (CVS) and amniocentesis.

What is the Prognosis of Chromosome 2p Deletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 2p Deletion Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. It may be assessed on a case-by-case basis, but it is generally difficult to predict the long-term outlook.

• Children with mild conditions (normally from small deletions) are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Weak muscle tone severity may determine motor function delays; it often improves with physiotherapy and as the child gets older
• Children usually require lifelong medical support and care

Additional and Relevant Useful Information for Chromosome 2p Deletion Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/