What Is AUTS2 Syndrome? Causes, Symptoms, and Treatment

AUTS2 syndrome is a rare genetic condition in which a change in one gene affects how the brain develops before and after birth.1PubMed Central. AUTS2 variant in a title diagnosed with autism spectrum disorder and intellectual disability disorder, a case report. It shows up mainly as delays in learning and development, often with autism-like traits and some recognizable physical features.2PubMed Central. AUTS2 variant in a title diagnosed with autism spectrum disorder and intellectual disability disorder, a case report. The gene’s name, short for “autism susceptibility candidate 2,” overstates its link to autism, and many children with the syndrome are not autistic. For families, one of the most reassuring points is that the condition does not usually get worse as children grow up.3The Transmitter. Analysis of syndrome weakens gene’s link to autism

What the AUTS2 Gene Does in the Developing Brain

Inside the cell’s control center, the AUTS2 protein helps switch on many genes the brain needs as it develops.4PubMed Central. AUTS2 Gene: Keys to Understanding the Pathogenesis of Neurodevelopmental Disorders It does this by turning a protein group that normally silences genes into one that activates them.5PubMed Central. AUTS2 confers gene activation to Polycomb group proteins in the CNS

In the rest of the cell, AUTS2 has a second job: it helps young nerve cells move to their proper place in the brain’s outer layer and grow their branches.6PubMed. Cytoskeletal regulation by AUTS2 in neuronal migration and neuritogenesis So when AUTS2 doesn’t work fully, both the wiring instructions and the physical positioning of brain cells can be affected.7PubMed Central. Neuronal Migration and AUTS2 Syndrome Because the gene manages many other genes, one change can touch several systems at once, so a child can have differences in learning, behavior, growth and facial features together.

The learning difference is usually called intellectual disability. That means lasting difficulty with learning, reasoning and everyday skills compared with other children the same age. In AUTS2 syndrome it ranges from mild to more severe.

The gene was first found in people with autism, but later studies showed autism traits in only about half of children with the syndrome. An autism diagnosis needs its own assessment.

A change in AUTS2 tells you which gene is involved, but not how one particular child’s learning, speech or behavior will turn out. Other genes, the exact nature of the change, and a child’s experiences and therapy all shape development, which is why children with the same diagnosis can differ a lot.

Common Symptoms and Features

These are the main features and how often each appeared in studied children:

These figures describe how often a feature appeared in groups of children who were studied, not what will happen to any one child. A child can have several of these features, only one or two, or a mix.

The developmental delay is often mild, and in one small group most children also had ADHD and autism traits together.13PubMed Central. Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation Speech and language can be especially delayed, sometimes severely.14PubMed. De novo single exon deletion of AUTS2 in a patient with speech and language disorder: A review of disrupted AUTS2 and further evidence for its role in neurodevelopmental disorders Autism estimates vary from about 40 in 100 to over half depending on the group studied.15Jordan Journal of Biological Sciences. A novel AUTS2 Variant in a Patient with Global Developmental Delay and Intellectual Disability Some children use gestures, pictures or devices before spoken words appear. Understanding often runs ahead of speaking, so a child may follow instructions better than they can answer. Early speech therapy is worth asking about as soon as a delay is noticed, rather than waiting to see whether the child catches up.

Many babies have a low birth weight and early feeding problems.16European Journal of Human Genetics. Two male adults with pathogenic AUTS2 variants, including a two-base pair deletion, further delineate the AUTS2 syndrome A baby may suck weakly, feed slowly or gain weight poorly, and older children may struggle with chewing or certain textures.

Facial features are usually mild but can include a short broad head, a small set-back chin, a wide nasal bridge and upturned nostrils.17PubMed. AUTS2-related syndrome: Insights from a large European cohort Most children have some delay in motor skills such as sitting and walking.18Simons Searchlight. AUTS2-related syndrome About half have brisk reflexes, and many walk on their toes with tight heel cords.19Simons Searchlight. AUTS2-related syndrome

Seizures occur in only some children, about 2 in 11 in one group.20Simons Searchlight. AUTS2-related syndrome They can look like stiffening and jerking, staring spells, or brief losses of awareness. Some happen mainly in sleep and change brain activity there. Any suspected seizure should prompt a doctor visit and possibly a brain-wave test (EEG).

What Causes AUTS2 Syndrome

The syndrome is caused by a change in one of the two copies of the AUTS2 gene.21PubMed Central. AUTS2 variant in a title diagnosed with autism spectrum disorder and intellectual disability disorder, a case report. The change can be a missing section, a doubled section, or a small spelling change in the gene’s code.22PubMed Central. Detection of copy-number variation in AUTS2 gene by targeted exonic array CGH in patients with developmental delay and autistic spectrum disorders Even a very small missing piece, removing just one part of the gene, can cause the syndrome.23PubMed. De novo single exon deletion of AUTS2 in a patient with speech and language disorder: A review of disrupted AUTS2 and further evidence for its role in neurodevelopmental disorders

In many reported children the change was de novo, meaning new in the child and not found in either parent.24PubMed. De novo single exon deletion of AUTS2 in a patient with speech and language disorder: A review of disrupted AUTS2 and further evidence for its role in neurodevelopmental disorders New gene changes happen randomly, so parents did nothing to cause it, and the chance of it happening again is often low, though not zero.

Everyone has two copies of most genes, one from each parent. Damage to just one copy is enough to cause this syndrome. If an affected adult has children, each child has a 1 in 2 chance of inheriting the change. Testing the parents tells the family whether the change is new or inherited.

The type of change also matters for testing. A missing or doubled section can be found by a microarray, while a tiny spelling change usually needs the gene’s code to be read to be seen. A genetic counselor can explain the report, and say what the chance of recurrence is in future pregnancies and whether siblings or other relatives should be tested.

How AUTS2 Syndrome Is Diagnosed

No single look or symptom confirms AUTS2 syndrome, so genetic testing is needed. Diagnosis often comes late, because the syndrome is rare and its features overlap with other conditions. A chromosomal microarray looks for missing or extra pieces of DNA and finds a cause in about 15 to 20 in 100 children with developmental conditions.25PubMed Central. AUTS2 Gene Variant Causing Intellectual Developmental Disorder, Autosomal Dominant 26 (MRD26): A Report of a Paediatric Case From the Arabian Peninsula Exome sequencing, which reads the code of nearly all genes, finds a cause in about 36 in 100, rising to 53 in 100 when there are extra physical features.26PubMed Central. AUTS2 Gene Variant Causing Intellectual Developmental Disorder, Autosomal Dominant 26 (MRD26): A Report of a Paediatric Case From the Arabian Peninsula

If a microarray came back normal, asking about exome sequencing makes sense. A normal microarray only rules out missing or extra pieces of DNA, not small spelling changes in the gene.

Your report may list the gene change (variant) as pathogenic, likely pathogenic, or of uncertain significance. Only pathogenic or likely pathogenic results confirm the diagnosis. An uncertain result may be reclassified later as more families are studied. After a diagnosis, the usual steps are a referral to a geneticist and often a neurologist and developmental pediatrician, baseline checks of growth, feeding and development, and testing the parents’ DNA.

Treatment and Therapies That Help

No medicine fixes the gene change, so treatment targets each child’s needs. A therapy team often includes several people:

The best starting point is usually the area causing the most difficulty, such as feeding trouble or very limited speech. A developmental pediatrician or the early intervention team can assess your child and suggest priorities, which can change as the child grows.

Children under 3 can often get free early intervention services in many countries, and school-age children may qualify for an individual education plan. A diagnosis letter helps secure these services.

Seizures, when they occur, are treated with seizure medicines like in other children. Some children, though, have a harder form of epilepsy with a lot of abnormal brain activity during sleep.31Elsevier / Seizure. Electroclinical features of epilepsy in AUTS2-related syndrome: case description and narrative review Seizures that change or don’t respond to treatment should be reviewed by a neurologist.

ADHD and autism traits can be managed with the usual behavioral approaches and, when suitable, medication. Consistent routines, clear short instructions and rewards for wanted behavior are usually tried first or alongside medication. If medication is considered, a doctor weighs the child’s age, other conditions and any seizures, since some medicines can affect seizure control. Parents can ask to start with one change at a time so it is clear what is helping and what is causing side effects.

Life Into Adulthood

Children with AUTS2 syndrome do not usually lose skills or decline as they grow up.32The Transmitter. Analysis of syndrome weakens gene’s link to autism Most adults have no chronic health problems.33The Transmitter. Analysis of syndrome weakens gene’s link to autism Mild skeletal problems such as a sideways curve of the spine (scoliosis) are common, though.34The Transmitter. Analysis of syndrome weakens gene’s link to autism A few adults have epilepsy, though it is unclear whether this comes from the gene change.35The Transmitter. Analysis of syndrome weakens gene’s link to autism

Scoliosis can appear or progress during growth, often before the teen years end. Signs include uneven shoulders or hips, or one side of the back looking higher when the child bends forward. Mild curves are often simply watched, and the doctor decides on bracing or other treatment only if the curve grows. Spine checks during growth spurts, ongoing review of seizures if present, and mental health support for anxiety or behavior are the checks worth keeping up.

Most adults will need some support with work, money or living. Planning for guardianship or supported decision-making can start in the teen years, and continued skill-building helps independence.

Finding Support as a Family

Caring for a child with AUTS2 syndrome is demanding, and families do better with a wide support network.36Citizen Health. AUTS2-related syndrome caregiver guide That can include relatives, friends, medical providers, therapists, other parents and community services.37Citizen Health. AUTS2-related syndrome caregiver guide Family registries such as Simons Searchlight connect families and gather information on the syndrome.38Simons Searchlight. AUTS2-related syndrome

Patient groups attached to a genetic clinic or a national rare-disease organization tend to be more dependable than anonymous posts. Medical advice from other parents may not fit your child, so check it with your child’s doctors. The genetic counselor may know of AUTS2 families or a local group, since clinics often know where to point you.

Parents need care too. Respite care gives you breaks, siblings may need their own attention and explanation, and counseling can help with grief after diagnosis.