Microcephaly

What Causes Microcephaly?

In many cases, the cause of microcephaly is unknown. In other cases, the condition seems to be caused by exposure to substances or situations that affect brain development, either before birth or during infancy. Some potential causes of microcephaly include:

• Infections in the mother during pregnancy. Some viral and bacterial infections may cause microcephaly if passed from the mother to the fetus during pregnancy. Infections that have been associated with the condition include toxoplasmosis, cytomegalovirus, German measles (rubella), chickenpox (varicella), and Zika virus.
• Pregnancy or delivery complications that cut off the oxygen supply to the baby
• Malnutrition of the mother during pregnancy
• Use of drugs or alcohol during pregnancy
• Exposure to toxic chemicals or radiation during pregnancy
• Premature closing of joints in the baby’s skull (craniosynostosis)
• Certain genetic conditions, such as Down syndrome
• Untreated phenylketonuria, an inherited metabolic disorder, in the mother

Is Microcephaly Hereditary?

Microcephaly is caused by an external event or condition (such as an infection) in many cases. However, in some cases, it is caused by abnormal changes (mutations) in specific genes, and these mutations sometimes may be inherited.

Inherited microcephaly is passed from parent to child in an autosomal recessive pattern, meaning that a child must inherit two copies of the gene mutation, one from each parent, to develop the disorder. People who have only one copy of the mutated gene will not develop the disease but will be carriers who can pass the mutation on to their children. Two carrier parents have a 25 percent chance of having a child with the disease with each pregnancy. Half of their pregnancies will produce a carrier, and a quarter of the pregnancies will produce a child with no mutated genes.

In some cases, microcephaly is inherited in an X-linked pattern, meaning that the mutated gene is located on the X chromosome. Females have two copies of the X chromosome, one inherited from each parent, but males have only one copy of the chromosome. Females are likely to have only one copy of the mutated gene, so they typically have no symptoms of the disorder. However, males who inherit a mutated gene have no normal copy to compensate, so they develop symptoms.

How Is Microcephaly Detected?

In some cases, microcephaly may be diagnosed before birth during ultrasound imaging exams. However, in many cases, the condition does not develop until later in pregnancy and may be undetectable until the third trimester.

How Is Microcephaly Diagnosed?

Microcephaly may be diagnosed when a physical exam shows an abnormally small head circumference. Doctors will take further diagnostic steps to rule out other possible causes for the abnormal growth and identify the underlying cause of the microcephaly.  The diagnostic process may include:

• Assessment of the child’s medical and family history
• Physical and neurological exams
• Imaging scans such as magnetic resonance imaging (MRI) or computerized tomography (CT) to assess the extent of brain malformation
• Blood and urine tests
• Genetic testing to look for genetic disorders associated with microcephaly

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Microcephaly Treated?

Mild cases of microcephaly may cause no significant impairments or symptoms. In these cases, no treatment beyond routine monitoring of the condition may be necessary. In more severe cases, treatments and therapies aim to lessen the impact of symptoms and prevent complications. Common treatments and therapies include:

• Anti-seizure medications
• Physical therapy
• Occupational therapy
• Special education

How Does Microcephaly Progress?

The outlook for children with microcephaly depends on the severity of the condition and any other conditions that are present. Potential long-term complications of microcephaly include:

• Intellectual disability
• Persistent problems with coordination and balance
• Speech impairments
• Short stature
• Facial malformations
• Hyperactivity
• Seizures

How Is Microcephaly Prevented?

Avoidance of risk factors during pregnancy can help decrease the risk of microcephaly:

• Get vaccinations as recommended by your doctor and take steps to avoid infections.
• Don’t use drugs or alcohol during pregnancy.
• Get good prenatal care to lessen the chance of birth complications.
• Eat a healthy diet during pregnancy.

Parents with a family history of genetic disorders associated with microcephaly are advised to consult a genetic counselor to assess their risk if they plan to have a child.

Microcephaly Caregiver Tips

• Be an advocate for your child. Learn all you can learn about microcephaly to understand the challenges your child faces, and be prepared to educate others about what they can do to help and support you and your child.
• Remember that you’re not alone. The Foundation for Children with Microcephaly offers support to families living with the disorder.

Some people with microcephaly also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with microcephaly:

• Children with microcephaly may be at increased risk of attention-deficit/hyperactivity disorder (ADHD).
• Some studies have associated microcephaly with autism spectrum disorder.

Microcephaly Brain Science

Recent research has determined that infection with the mosquito-borne Zika virus can cause microcephaly, along with several other congenital disabilities. A mother infected with the virus during pregnancy can pass the infection to the fetus, and a cluster of symptoms called congenital Zika syndrome can result. Symptoms of the syndrome may include:

• Severe microcephaly with significant malformation of the skull
• Shrinkage of brain tissue
• Brain malformations such as hypoplasia of the cerebellum or smooth brain
• Accumulation of calcium in the brain
• Damage to the retinas in the eyes
• Limited joint mobility
• Rigid muscle tone
• Cerebral palsy
• Epilepsy
• Low birth weight
• Vision and hearing impairment

Microcephaly Research

Title: Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay

Stage: Recruiting

Principal investigator: Stephanie C. DeLuca, PhD

Virginia Polytechnic Institute and State University

Roanoke, VA

Up to 50 children between the ages of 6 months and 15 years will be recruited to participate in a burst of intensive neuromotor intervention in the form of Acquire therapy, delivered by the treatment team at Virginia Tech’s Neuromotor Research Clinic. All children will have a diagnosis of Global Developmental Delay, with concomitant microcephaly or hyperkinetic movements. The children will be assessed for psychomotor function before and after the treatment intervention, using a series of standardized and goal-specific assessments, with the possibility of additional neuroimaging assessments when possible. Acquire therapy is an intensive intervention in that it is delivered with high intensity, wherein goal-directed behaviors are promoted at high levels of repetition and delivered at a high dose (4-6 hours a day) in an intensive burst of 3-4 weeks of 5 days a week treatment. Acquire therapy is an operant conditioning-based intervention delivered in a cycle of refinement, reinforcement, and repetition. It is play-based with activities selected to drive behavior toward goals specific to each child and selected based on their interests and needs. As such, a specific protocol cannot be outlined. However, all goal-directed activities are designed to promote awareness of and engagement with others and the environment.

Title: The FBRI VTC Neuromotor Research Clinic

Stage: Recruiting

Principal investigator: Stephanie C. DeLuca, PhD

Virginia Polytechnic Institute and State University

Roanoke, VA

The FBRI VTC Neuromotor Research Clinic was established and opened in May 2013 to provide intensive therapeutic services to individuals with motor impairment secondary to neuromotor disorders. It is direct by Dr. Stephanie DeLuca and based on the principles surrounding ACQUIREc Therapy.

ACQUIREc Therapy is an evidence-based approach to pediatric constraint-induced movement therapy, which refers to a multi-component form of therapy focused on helping children with asymmetric motor abilities between the two sides of the body. Historically, ACQUIREc Therapy has the unimpaired or less impaired upper extremity constrained (by a cast or a splint) while also receiving active therapy from a specially trained therapist who shapes new skills and functional activities with the child’s more impaired upper extremity.  The therapist is also a licensed Occupational or Physical Therapist (OT/PT). Therapy dosages are much higher than traditional OT or PT – often lasting many hours per day, up to 6 hours a day, five days a week, for 2-4 weeks.

Investigators have developed further treatments based on the same principles of intensive services combined with behavior shaping for other body areas that are also affected by weakness (e.g., the leg and trunk) but which usually do not involve constraint. These have been more generally labeled ACQUIRE Therapy.

All forms involve intensive, play-based therapy for children with asymmetric motor impairments of the arms and hands. The primary focus of treatment is to facilitate the acquisition of new motor skills in the child’s weaker body parts through high levels of intensive therapy using scientifically-based behavioral guidelines. Therapy is also delivered in naturalistic environments.

ACQUIREc Therapy as a treatment method has been tested in two randomized controlled trials, and a specific manual for its implementation has been developed. Dr. (s) Ramey and DeLuca previously founded a similar clinic, The Pediatric Neuromotor Research Clinic, at the University of Alabama at Birmingham, is where Dr. DeLuca directed the research clinic for 13 years and oversaw the implementation of the ACQUIREc Therapy treatment protocol in more than 400 cases.

This research will involve analyzing and interpreting the clinical data of children going through clinical procedures at the FBRI VTC Neuromotor Research Clinic. All participation is voluntary, and no children will be denied services if families choose not to participate.

Title: Neurodevelopmental Outcomes in ZIKV-Exposed Children

Stage: Enrolling by invitation

Principal investigator: Sarah B. Mulkey, MD, PhD

Children’s National Research Institute

Washington, DC

Zika-virus (ZIKV) infection in pregnancy can result in severe brain damage in 4-12% of cases. Children exposed to ZIKV in utero during the years of 2015-2017 are now in early childhood. Children with severe neurologic injury (Congenital Zika Syndrome; CZS) have a poor developmental outcome. However, the developmental outcome of apparently normal infants following in utero ZIKV-exposure is not well known. In addition, the incidence of abnormal neurodevelopmental outcomes in seemingly normal children with in-utero ZIKV-exposure is not known.

The investigators will determine if neurodevelopmental assessment scores in children exposed to ZIKV in utero who are normal-appearing differ from norms. The investigators hypothesize that ZIKV-exposed normal appearing children will have lower multi-domain developmental assessment scores than normative samples. In addition, the investigators hypothesize that the presence of mild postnatal non-specific cranial US findings is associated with persistent lower developmental assessment scores compared to ZIKV-exposed children who had normal cranial US, and quantitative imaging will find structural and functional brain differences between ZIKV-exposed children and controls.

The investigators will perform a prospective developmental outcome study at two sites: 1) Department of Atlántico, Colombia through collaboration with BIOMELAB, the research center of Dr. Carlos Cure, and 2) Children’s National, Washington, DC.

The study’s objective is to determine whether children exposed to ZIKV in utero and who do not have CZS have abnormalities in neurodevelopment during early childhood and at school age.

The primary outcome in early childhood will be neurodevelopmental assessment scores at age 3 and 4 years. Scores will be compared between Zika-exposed children and controls. The primary outcome at school age will be neurodevelopmental assessment scores at age 5 and 7 years and quantitative brain MRI at seven years.