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

• 1q Duplication Syndrome

What is Chromosome 1q Duplication Syndrome? (Definition/Background Information)

• Chromosome 1q Duplication Syndrome is a rare chromosomal disorder caused by the presence of an extra copy of a small piece of chromosome 1 in the cells of the body 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 gained (duplicated), the number of genes affected, and the function of the affected genes
• The condition affects newborn children (congenital manifestation). In 1q Duplication Syndrome, there is duplication of chromosomal material on the long arm (q) of one of the chromosomes 1. Every cell has two copies of chromosome 1s. Typically, small duplications do not present any major or significant health concerns. When large duplications are noted, the presentations may be severe, especially learning difficulties
• It can result in developmental delays, heart and brain abnormalities, seizures, and vision impairment. Chromosome 1q Duplication Syndrome may present complications such as malnutrition due to feeding difficulties, delayed achievement of milestones, kidney and urinary bladder system defects, 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). 1q Duplication 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 vision and hearing aids, seizure control, physiotherapy, and surgery for correction of heart and other defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 1q Duplication 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 1q Duplication Syndrome? (Age and Sex Distribution)

• The incidence of Chromosome 1q Duplication Syndrome is unknown. It is a rare disorder
• 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
• The presentation of symptoms may occur at or following the birth of the child
• Both males and females are affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Chromosome 1q Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 1q Duplication Syndrome.

• In some individuals, a positive family history may be an important risk factor for 1q Duplication 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 1q Duplication Syndrome? (Etiology)

Chromosome 1q Duplication Syndrome is caused by the presence of extra chromosomal material on the long arm (q) of chromosome 1. The amount of chromosome material added/duplicated varies widely from one individual to another resulting in a variable set of signs and symptoms.

• There are two chromosomes numbered 1. Children with 1q Duplication Syndrome typically will have one (chromosome 1) in normal condition, while the other is abnormal. The abnormality is characterized by a gain of chromosomal material
• The duplications may be termed distal (occurring towards the tip of the chromosome arm), proximal (closer to the center of the chromosome), or telomeric (towards the tip). The signs and symptoms may vary based on the location of the duplication
• It is observed that when the duplication of material occurs at the tip of the chromosome, the conditions are generally mild. In severe cases, where large duplications are noted (or the centromere is involved), the child may be severely affected
• When complete duplication of chromosome 1q is noted, the condition is termed trisomy; however, this is extremely rare and only over 30 trisomy cases have been reported
• In 80% of the cases, the involvement of another chromosome is seen. Here, either genetic material of another chromosome is missing, or a duplication has taken place

Most cases of the disorder develop sporadically (de novo) during embryonic development. This means that no duplication of genetic material at 1q is observed in either of the parents.

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

What are the Signs and Symptoms of Chromosome 1q Duplication Syndrome?

The signs and symptoms of Chromosome 1q Duplication 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 added and the number of genes affected. As a general rule, a small gain in chromosome material generally results in milder signs and symptoms. Conversely, larger gains/duplications 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 gains, may have disproportionately severe presentations.

The associated signs and symptoms depend on what material is duplicated, how much duplication has occurred (quantity), where the duplications occurs (such as at the tip or center of the chromosome), and if the involvement of another chromosome is noted (known to occur in a majority of cases).

The commonly noted signs and symptoms of Chromosome 1q Duplication Syndrome include:

• In some children, large-sized or small-sized head with respect to the body is noted
• Distinctive facial features may include receding small lower jaw and small chin; low-set ears and nose abnormal in appearance (making it difficult to wear normal glasses), although hearing is generally unaffected
• Short stature
• Dental anomalies that include an early or late eruption of teeth
• Severe feeding difficulties (including due to abnormal jaw structure)
• High, narrow, and/or split (cleft) palate
• Hand and foot joints may be in bent or fixed position
• Presence of abnormal hands and feet (such as slender hands, conjoined toes, unusual placement of digits, extra digits, etc.)
• Speech delays and learning disabilities, which may be highly variable based on the amount and location of duplication of chromosome material
• Fontanelle: A large soft spot on head/skull that closes slowly
• Hydrocephalus, the presence of excess cerebrospinal fluid around the brain, is commonly seen
• The following heart abnormalities 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
  • Hypertrophic cardiomyopathy
  • Wolff-Parkinson-White syndrome
  • Structural defects such as patent foramen ovale (PFO) and patent ductus arteriosus (PDA)
  • Double outlet right ventricle
  • Coarctation of the aorta
  • Valve defects such as atrial septal defect (ASD)
  • Pulmonary stenosis
  • Tetralogy of Fallot, an abnormality that consists of four heart defects, namely subpulmonic stenosis, ventricular septal defect, overriding aorta, and right ventricular hypertrophy
  • Ebstein’s anomaly: It is a rare congenital heart defect that causes the tricuspid valve to leak blood backwards into the right atrium
• Seizures in some children
• Digestive system abnormalities such as:
  • Omphalocele
  • Intestinal malrotation
  • Meckel’s diverticulum
  • Constriction of the esophagus (food-pipe)
• Vision impairment due to optic nerve defects and other structural defects; strabismus is commonly noted
• In some boys, genital anomalies such as undescended testicles, micropenis, hypospadias, and abnormal scrotum may be observed

How is Chromosome 1q Duplication 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 1q Duplication Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

1q Duplication 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
• Neurological examination that involves the central nervous system (brain and spinal cord); brain scans
• 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 1q Duplication Syndrome?

When abnormalities (large duplications) are noted that also involve the centromere, severe birth defects and reduced life expectancies are noted. This may also result in fetal death during pregnancy 

The complications of Chromosome 1q Duplication Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Failure to thrive
• Weak immune causing severe vulnerability to respiratory tract infections
• Delayed milestone achievement; walking may be around age 24 months
• Severe cases of hydrocephalus may cause the brain tissues to shrink
• Chiari malformation when part of the brain extends into the spinal column
• Vision loss (partial or total blindness)
• Poor growth due to malnutrition caused by weak suckling
• Pituitary gland abnormalities
• Kidney and urinary tract abnormalities including single kidney, small-sized or abnormal kidneys, and ureteral obstruction
• Severe heart anomalies
• Reduced quality of life

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

How is Chromosome 1q Duplication Syndrome Treated?

There is no cure for Chromosome 1q Duplication 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 1q Duplication Syndrome may involve:

• Use of hearing aids, if required
• 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
• Employing 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
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time
• Surgical treatment for hydrocephalus
• 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
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Pituitary gland dysfunction may require growth hormone therapy
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy

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

How can Chromosome 1q Duplication Syndrome be Prevented?

Chromosome 1q Duplication 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 1q Duplication 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 1q Duplication Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 1q Duplication 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, especially on a long-term basis.

• Children with mild conditions (usually from small duplications) are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Some of the abnormalities involving the heart, seizures, recurrent infections, motor skills, communication and behavioral issues are known to resolve or improve with time
• Children usually require lifelong medical support and care. It is informed that the growth progression depends on proper feeding and extent of severity of heart abnormalities

In a majority of cases, pregnancy and delivery are at full term and normal; the child birth weight is also normal for gestation.

Additional and Relevant Useful Information for Chromosome 1q Duplication Syndrome:

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

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