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

• 3p26 Deletion Syndrome

What is Chromosome 3p26 Deletion Syndrome? (Definition/Background Information)

• Chromosome 3p26 Deletion Syndrome is a rare chromosomal disorder that develops when there is missing genetic material on chromosome 3 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 condition affects newborn children (congenital manifestation)
• It can result in low birth weight, developmental delays, poor motor skills, heart and kidney abnormalities, seizures, and vision and hearing impairment. Chromosome 3p26 Deletion Syndrome may present complications such as failure to thrive, delayed achievement of milestones, mental health disorders, and a reduced quality of life
• This chromosomal anomaly may develop from sporadic mutations (majority of cases), or it may be inherited from one’s parents (very rarely). 3p26 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 speech and learning assistance, vision and hearing aids, seizure control, physiotherapy, and surgery for correction of abnormalities
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 3p26 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 3p26 Deletion Syndrome? (Age and Sex Distribution)

• Chromosome 3p26 Deletion Syndrome is an extremely rare congenital disorder. Only a few cases have been reported in the medical literature
• Individuals with mild signs and symptoms may be undiagnosed in their lifetime. Hence, a true incidence of the disorder may be difficult to estimate
• The presentation of symptoms may occur at or following the birth
• 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 3p26 Deletion Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 3p26 Deletion Syndrome.

• In some individuals, a positive family history may be an important risk factor for 3p26 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 3p26 Deletion Syndrome? (Etiology)

Chromosome 3p26 Deletion Syndrome is caused by deletion of genetic material from the short arm (p) of chromosome 3 at band p26; 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 3. Children with 3p26 Deletion Syndrome typically will have one (chromosome 3) in normal condition, while the other is abnormal. The abnormality is characterized by a loss of chromosomal material.

• Most cases of the disorder develop sporadically (de novo) during embryonic development. This means that no deletion of genetic material at 3p26 is observed in either of the parents. However, in rare cases, Chromosome 3p26 Deletion Syndrome may be inherited
• The type of deletion that takes place is termed “distal”, meaning the deletion occurs away from the center of the chromosome, and is closer to the tip of the p arm. Individuals with this deletion may be missing any, some, or all of the genetic material at locus 26 (which is further subdivided into bands 26.1, 26.2 and 26.3)
• The forms of deletions that are known to take place include terminal deletions, when the tip/end of the chromosome is lost; and interstitial deletions, where a certain length of the short arm of chromosome is missing, but the tip/end is still present. Based on this, the disorder is categorized into the following groups:
  • Group 1: 3p26.1 and 3p26.2 terminal deletions
  • Group 2: Deletions from 3p26.3 (either terminal or interstitial deletions are noted); many cases are inherited

The associated signs and symptoms of Group 1 and Group 2 may vary significantly between them.

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 3p26 Deletion Syndrome?

The signs and symptoms of Chromosome 3p26 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 associated signs and symptoms depend on what material is missing/lost, how much deletion has occurred (quantity), where the deletions occur, and if the involvement of other chromosomes are noted.

The commonly noted signs and symptoms of Chromosome 3p26 Deletion Syndrome include:

• Poor muscle tone (hypotonia) causing motor delays that can be mild or severe is common, and may include:
  • Feeding problems (sucking and swallowing) leading to small and underweight children
  • Difficulty in holding small items such as a cup or spoon
  • Drawing and writing difficulties
  • Difficulty in climbing stairs and difficulty in sitting without support
  • Standing and walking difficulties
  • Help needed for wearing clothes and undressing
• Gastroesophageal reflux disease (GERD)
• Developmental delays
• Facial feature abnormalities:
  • Small-sized head (microcephaly)
  • Wide-spaced eyes and droopy upper eyelid
  • Cleft palate
  • Tiny holes in the cheek, in front of the ears
  • Prominent nasal bridge
• Presence of abnormal hands and feet (such as extra digits)
• Short stature
• Seizures may be observed in infants and young children
• Vision defects may include:
  • Strabismus
  • Shortsightedness
• Breathing issues in children (mostly sleep apnea)
• Congenital hip dislocation that may involve one or both hips
• Hearing impairment
• Heart abnormalities (such as a hole in the heart) may be observed. This can result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others
• Speech and learning disabilities
• Digestive system (internal) abnormalities
• Sleep disturbances that can affect one’s physical and mental health
• Constipation that may be moderate to severe
• Behavioral problems

How is Chromosome 3p26 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 1q4 Deletions in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 3p26 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
  • Tympanometry: A test that puts air pressure in the ear canal in order to move the eardrum, and then measures the eardrum mobility (movement)
• 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
  • Alignment and focusing testing
  • Fundoscopic (ophthalmoscopic) examination by an eye specialist, who examines the back part of the eye (or the fundus)
  • Slit-lamp examination
  • Visual evoked potential (VEP) test
  • Fundus fluorescein angiography
  • Optical coherence tomography (OCT) of eye
• Evaluation of heart defects through:
  • Chest X-rays
  • Echocardiogram
  • Electrocardiogram (EKG)
  • Cardiac catheterization
  • Fetal ultrasound for heart defects
• 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
• Kidney and urinary tract scans
• Brain scans (to determine corpus callosum): These may include prenatal ultrasounds and MRI scans, and CT/MRI scans after development of the child
• 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 3p26 Deletion Syndrome?

The complications of Chromosome 3p26 Deletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR); babies are underweight at birth
• Failure to thrive
• Delayed milestone achievement that may affect when a child rolls, sits, crawls, or walks
• Brain anomalies including hydrocephalus, large brain ventricles, and delayed myelination
• Sleep apnea may be associated with seizures (night-time seizures)
• Poor growth due to malnutrition caused by weak suckling
• Risk of falls and injury due to seizures
• Speech disorder
• Kidney defects
• Deafness
• Autism spectrum disorders
• Increased risk for pneumonia in children with gastroesophageal reflux disease (GERD)
• Severe heart anomalies
• Severe cognitive impairment; low IQ levels
• Reduced quality of life

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

How is Chromosome 3p26 Deletion Syndrome Treated?

There is no cure for Chromosome 3p26 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 Chromosome 3p26 Deletion Syndrome may involve:

• Use of hearing aids, as needed
• Seizure control using anticonvulsant medication, vitamin supplements, and ketogenic diet
• Special education: Employing suitable learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition. Writing by holding a pencil may be very difficult; but touchscreen computers and keyboards are known to be easier to use and learn
• Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
• Physiotherapy for weakened muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, hydrotherapy, 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 and shoe inserts; wheelchair assistance may be necessary
• For feeding difficulties, use of feeding tubes (temporary nasogastric or gastrostomy tubes), medications, feed thickeners, bottle-feeding expressed milk, including special diets and nutritional supplements
• A surgical procedure named fundoplication may be necessary in some children with severe GERD. Milder GERD cases can be generally well-controlled by giving feeds slowly and positioning the baby in a semi-upright. And, where necessary, raising the head of the end of the bed for sleeping is also recommended
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time without any invasive procedures
• Surgical correction of physical defects, as assessed by a healthcare expert, such as surgical repair of cleft lip
• Use of suitable glasses and surgical rectification of vision defects, if necessary
• Sleep disorders may require medication; daytime naps may be advised
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Social skills training support groups and exercises
• Occupational therapy

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

How can Chromosome 3p26 Deletion Syndrome be Prevented?

Chromosome 3p26 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 (chromosome) 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 3p26 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 3p26 Deletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 3p26 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 are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• However, many children require prolonged medical support and care

Additional and Relevant Useful Information for Chromosome 3p26 Deletion Syndrome:

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

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