ASD, also known as Autism Spectrum Condition (ASC), is a generalized developmental disorder caused by differences in brain development, symptoms of which include abnormal language and communication skills, narrow interests, and repetitive behavior patterns.^[1] Additionally, people with ASD may have different ways of learning, moving, or paying attention. In 2013, the fifth edition of the Diagnostic Statistical Manual of Mental Disorders (DSMV) in the United States revised the diagnostic criteria for autism and related disorders, canceling the original designation of 'Autism' and updating its classification into Autism Spectrum Disorder (ASD). ASD is an umbrella term which includes autism disorder (classically-known as autism), Asperger's syndrome (AS), pervasive developmental disorder, not otherwise specified (PDD-NOS), and childhood disintegrative disorder (CDD).^[2] Usually, what people refer to as autism more accurately refers to ASD, which is autism in a broad sense.

The specific pathogenic mechanism of ASD is unknown. The mainstream view is that it is mainly related to genetics and environment. Data shows that ASD is a highly heritable disease, and the monozygotic twin concordance rate is as high as 90%. A meta-analysis published in 2016 reported that 74-93% of autism risk is heritable, and studies of siblings in the same family showed that after an older child was diagnosed with ASD, subsequent children had a 7 -20% chance of developing ASD.^[3] More than 1,000 genes have been found to be associated with ASD genetic risk, most of which are closely related to normal neural development and connectivity between different functional regions of the brain, suggesting a common pathway leading to ASD risk. ^[4] Genetic abnormalities associated with ASD can be divided into three categories:

1. Single gene mutations: such as mutations found in SHANK3, FMR1, or MECP2;

2. Copy number variations (CNVs): including chromosomal duplications, large deletions, inversions, and translocations;

3. Polygenic risk factors: caused by the accumulation of multiple variants. However, the primary causative gene(s) and specific type of mutation is still under further research.

The current global incidence of ASD is about 0.6%-1%. In the United States, 1 in 68 children is affected by ASD, and the incidence frequency of boys is 4.5 times that of girls. ASD typically begins before age 3 and lasts a lifetime. As children with ASD grow into adolescents and adults, they have extreme difficulty developing and maintaining friendships or communicating with others, along with symptoms such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD).^[5] At present, the treatment of ASD is mainly symptomatic treatment, mainly aimed at symptoms that interfere with daily function and quality of life. Since ASD affects everyone differently, each patient has different treatment needs and the therapeutic strategies usually involve multiple professional fields. Since the pathogenic mechanism is still unclear, there is currently no etiological treatment or preventative for ASD, and more research on the pathology of ASD is urgently needed.

Tbx1 Mice (E1-E2 knockout)

Figure 1. Tbx1 heterozygous mice (HT) exhibited ASD-related behavioral phenotypes
left: frequencies and durations of vocalizations
right: T-maze spontaneous alternation behavior (SAB)[6]

Shank3B Mice (E13-E16 knockout)

Figure 2. Shank3B^-/- mice have reduced social interaction and abnormal social novelty recognition^[7]

Cntnap2 Mice (E1 knockout)

Figure 3. Cntnap2^-/- mice exhibit an ASD phenotype with abnormal communication and social behavior^[8]