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

• 3q13 Deletions and Microdeletions Syndrome

What are Chromosome 3q13 Deletions and Microdeletions? (Definition/Background Information)

• Chromosome 3q13 Deletions and Microdeletions is a rare and emergent chromosomal disorder that develops when there is missing genetic material on chromosome 3 (on long arm q at position q13) 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 development delays, abnormal facial features, low muscle tone, seizures, and vision impairment. Chromosome 3q13 Deletions and Microdeletions 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). 3q 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 of 3q13 Deletions and Microdeletions Syndrome, 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 aids, seizure control, speech and language therapy, physiotherapy, and surgery for correction of heart and other physical defects, if any
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 3q13 Deletions and Microdeletions 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

Individuals with 3q13 abnormalities are broadly categorized into the following four main groups based on the location of the chromosomal deletion/microdeletion:

• Group 1: The loss of genetic material (DNA) is between 3q13.2 and 3q13.31; prominent among this group is chromosome 3q13.31 deletion syndrome
• Group 2: It overlaps with Group 1 and involves the loss of a greater amount of genetic material than individuals within Group 1; the loss occurs between 3q13.11 and 3q13.33
• Group 3: In Group 3 individuals, the deletion may occur between the chromosome bands 3q13.13 and 3q13.31
• Group 4: Genetic material loss is seen between 3q13.2 and 3q13.33 (extending almost to the tip of the chromosome arm)

Who gets Chromosome 3q13 Deletions and Microdeletions? (Age and Sex Distribution)

• Chromosome 3q13 Deletions and Microdeletions is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• 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
• 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 3q13 Deletions and Microdeletions? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 3q13 Deletions and Microdeletions.

• In some individuals, a positive family history may be an important risk factor for 3q 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 3q13 Deletions and Microdeletions? (Etiology)

• Chromosome 3q13 Deletions and Microdeletions is caused by deletion of genetic material from the long arm (q) of chromosome 3
  • In most cases, this deletion occurs de-novo (spontaneously)
  • In some cases, the deletion can be inherited (a positive family history of the condition may be noted)
• There are two chromosomes numbered 3. Children with Chromosome 3q Deletions typically will have one (chromosome 3) in normal condition, while the other is abnormal. The abnormality is characterized by a loss of chromosomal material at the band location q13
• Individuals with 3q13 deletions are further grouped as Group 1, Group 2, Group 3, and Group 4, based on the position and amount of genetic material deletion, with widely varying signs and symptoms
• In some cases, microdeletion involves genetic material at band q13.31; in which case, the condition is termed 3q13.31 deletion syndrome (belonging to Group 1). This is an emerging syndrome that was discovered recently (in 2012). Tiny microdeletions can occasionally be inherited directly from either parent. Such inheritance patterns have not been observed with 3q13.31 deletions, which are known to arise spontaneously without apparent cause
• Within individuals exhibiting recurrent 3q13 microdeletions, it is hypothesized that one cause of the microdeletion stems from short DNA stretches at both ends of the deletion, which bear a striking resemblance to each other
• In microdeletion, a very tiny part of the chromosome is lost or missing; when it is not even visible under a microscope with high magnification. In such cases, FISH or array-CGH studies may be necessary to detect the deletions
• An involvement of the following genes is reported, depending on the deletion point on the q13 band:
  • DRD3 gene
  • GAP43 gene
  • LSAMP gene
  • ZBTB20 gene

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 3q13 Deletions and Microdeletions?

The signs and symptoms of Chromosome 3q13 Deletions and Microdeletions may be significantly different from one individual to another. Signs and symptoms are often related to the amount of chromosome material deleted (including the breakpoint) and the number of genes affected (varying from Group 1 to 4). 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 chromosomal loss may have disproportionately severe presentations.

The commonly noted signs and symptoms of Chromosome 3q13 Deletions and Microdeletions include:

• Developmental delays
• Children who are small at birth may have relatively rapid growth rate with large head size and overweight body
• Poor muscle tone; floppy baby
• Newborns may have difficulty feeding (swallowing and suckling difficulties), and establishing breastfeeding can be problematic, especially during the initial days
• Presence of gastroesophageal reflux disease (GERD)
• Constipation is commonly observed in small children
• Poor and/or delayed fine motor skills
• Presence of abnormal hands and feet (including flatfeet, talipes equinovarus, claw foot, and widely spaced toes)
• Intellectual disability and behavioral issues such as anxiety, short attention span, aggression, and risky behavior
• Distinctive facial features such as:
  • Small or large sized head; broad forehead
  • Widely-spaced eyes; eyes may slant downwards; eyebrows may be very thin
  • Ear abnormalities
  • Prominent and broad nose; nose may be upturned
  • Nose and mouth may be unusually closer to each other
  • Lower lip may appear fuller (larger than normal)
  • High palate
  • Pointed chin
• Epileptic seizures may be noted in many children
• Vision impairment (such as strabismus, nystagmus, cataracts, shortsightedness and longsightedness)
• Speech and communications problems
• Learning disabilities
• Heart abnormalities in a few children that may include persistent ductus arteriosus (PDA), patent foramen ovale (PFO), and tetralogy of Fallot
• Minor genital abnormalities may be noted in some boys such as small genitalia and undescended testes
• Sleep disturbances
• Dental disorder and teeth abnormalities are not uncommon

Individuals may also present the following signs and symptoms based on their categorized group.

Group 1

• Low amniotic fluid during pregnancy in some cases
• Children show significantly less stability on their feet compared to normal children
• Children and adults are generally tall for their age and overweight (unlike those belonging to other groups)
• Delayed speech development and stuttering
• Mental health issues in some children include anxiety, brief attention spans, low energy levels, limited ability to cooperate, aggression, and frustration
• Obsessive-compulsive behaviors including excessive handwashing
• Over 30% present foot defects
• Constipation in some cases

Primary characteristics of the 3q13.31 deletion syndrome encompass:

• Developmental delays, spanning mobility and speech milestones.
• Accelerated growth rate in infants and children, including an enlarged head circumference
• Reduced muscle tone (hypotonia), resulting in a floppy sensation when holding the baby
• Underdeveloped genitalia in boys; girls may exhibit normal genital development
• Abnormal facial features
• Ptosis or droopy eyelids, which may be severe
• Elevated palate (roof of the mouth)

Less frequently observed traits of 3q13.31 deletion syndrome may include:

• Vision impairments such as nearsightedness or farsightedness
• Involvement of the brain and central nervous system
• Occurrence of seizures and/or atypical brain electrical activity patterns
• Small hands, short or long fingers that may taper; thumb may be close to the wrist; gripping and holding objects may be difficult for some

Dental issues observed in children with a 3q13.31 deletion include crowded teeth, severe dental caries, small and misaligned teeth, black spots from excessive drooling, and teeth grinding.

Group 2

• Smaller babies than those in Group 1, although some babies may be abnormally tall
• Low energy during infancy and poor muscle tone
• Children show significantly less stability on their feet compared to normal children
• Children in Group 2 may need a higher level of learning support compared to those in Group 1
• Mental health issues in some children include anxiety, brief attention spans, low energy levels, limited ability to cooperate, aggression, and frustration

Group 3

• Some babies are observed to be small-sized at birth
• Mobility issues (crawling, walking) were noted in young children (6-22 months) with low muscle tone; unusual gait
• Few children presented learning disabilities

Group 4

• Some children may be tall with a large head size
• Children may require extensive assistance due to speech and learning disabilities

How are Chromosome 3q13 Deletions and Microdeletions 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 3q13 Deletions and Microdeletions in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 3q13 Deletions and Microdeletions 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 and vision assessment through various tests
• 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 through various exams
• 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 3q13 Deletions and Microdeletions?

The complications of Chromosome 3q13 Deletions and Microdeletions (generally among all groups) may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications are infrequently noted (they typically do not arise from this chromosomal abnormality)
• Failure to thrive
• Delayed milestone achievement; this may be a significant issue in children with Chromosome 3q13.31 Deletion Syndrome
• Brain abnormalities such as:
  • Agenesis/hypoplasia of the corpus callosum
  • Delayed myelination
  • Abnormally-enlarged ventricles
• Risk of falls and injury due to seizures
• Abnormal spinal curvature (scoliosis, kyphosis, or lordosis) is not uncommon in children with poor muscle tone
• Kidney and urinary tract anomalies (rarely)
• Severe disability such that normal day-to-day activities become difficult
• Fertility may be affected in some males
• Reduced quality of life

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

Group 1 complications may include:

• Some babies at birth may be underweight, have low Apgar scores, and face breathing issues and feeding difficulties, including latching problems.
• In some with 3q13.31 deletion syndrome, partial or complete absence of the band of nervous tissue connecting the brain's hemispheres, a condition termed agenesis/hypoplasia of the corpus callosum (HCC or ACC), may be seen. The condition may be mild or severe
• Normal intellectual development may be affected
• Seizures in children and adults
• Kidney and urinary tract abnormalities are sometimes observed.
• Certain children are more susceptible to recurrent upper respiratory tract infections during early childhood and may require hospitalization. However, as they progress into later childhood, they typically outgrow this tendency and enjoy good overall health

Group 2 complications may include:

• Kidney and urinary tract abnormalities are sometimes observed.
• Respiratory distress in some babies
• Difficulty with fine motor skills
• Significant delays in speech development: Children often depend on body language and non-verbal communication to convey their needs and emotions. Some children may start using words relatively late, typically around 6 to 8. However, their verbal communication may not be clear or easily understandable to many
• Seizures in children that tend to get better as they grow
• Chronic lung disease
• Hypothyroidism
• Tracheomalacia: Weakened tracheal cartilage, leading to airway collapse
• Laryngomalacia: Collapse of the laryngeal tissues causing breathing difficulties, especially during infancy

Group 3 complications may include:

• Preterm birth
• Respiratory distress in some babies
• Occasionally, children may present severe birth defects
• Generalized seizures at a very young age (beginning after 12 months) that responded to anticonvulsants

Group 4 complications may include:

• Severe respiratory distress in some babies
• Seizures in children

How are Chromosome 3q13 Deletions and Microdeletions Treated?

There is no cure for Chromosome 3q13 Deletions and Microdeletions 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. The treatments may vary based on their categorized group (Group 1, 2, 3, or 4). 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 3q13 Deletions and Microdeletions may involve:

• 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, 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
• Children who display significant flexibility and laxity in their joints or demonstrate tightness and contractures in some joints may require timely intervention to attain mobility. Lower limb support in splints, ankle-foot orthoses, supportive boots, and overall body support in standers or walkers may be necessary
• 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 gastroesophageal reflux disease (GERD). Milder GERD cases can be generally well-controlled by giving feeds slowly and positioning the baby in a semi-upright position. 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, such as patent ductus arteriosus, tend to improve over time without any invasive procedures
• Surgical correction of physical defects, as assessed by a healthcare expert
• 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 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 3q13 Deletions and Microdeletions be Prevented?

Chromosome 3q13 Deletions and Microdeletions 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 3q13 Deletions and Microdeletions 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 3q13 Deletions and Microdeletions? (Outcomes/Resolutions)

The prognosis of Chromosome 3q13 Deletions and Microdeletions is depends 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 (usually from small deletions) are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Some children require prolonged medical support and care

In cases where both parents possess normal chromosomes, the likelihood of another child being born with a 3q13 deletion, or any other chromosome disorder is low. However, in rare instances (less than 1%), although both parents exhibit normal chromosomes in blood tests, a small fraction of their egg or sperm cells may carry the 3q13 deletion. In this phenomenon, known as germline mosaicism, parents may have normal blood tests but may still have multiple children with the deletion.

Additional and Relevant Useful Information for Chromosome 3q13 Deletions and Microdeletions:

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

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