Publications about genetic testing for neurological disorders
  1. Syndromic Autism Gene Panel

Syndromic Autism Gene Panel

June 15, 2018

Disease summary:

Autism spectrum disorders (ASD) are a clinically heterogeneous group of disorders that share common features of impaired social relationships, language and communication skills, as well as repetitive behaviors or a specific and very narrow range of interests. Symptoms develop gradually, and about 50-70% of children with autism are identified as intellectually disabled1 with lifelong disability requiring intensive parental, school, and social support 2, 3.

Autism can be associated with a syndromic phenotype, commonly characterized by dysmorphic features, microcephaly and seizures.

In 20-25% of cases with autism a genetic cause can be identified2-7. Chromosomal disorders (~5%), copy number variants (CNVs; chromosomal microdeletions and duplication syndromes) (10–20%), and single-gene disorders (~5%) 8. Pathogenic variants in many single genes have been associated with autism, including genes AP3B1, BLOC1S3, BLOC1S6, C10ORF11, DTNBP1, EDN3, EDNRB, GPR143, HPS1, HPS3, HPS4, HPS5, HPS6, KIT, LYST, MC1R, MITF, MLPH, MYO5A, OCA2, PAX3, RAB27A, SLC24A5, SLC45A2, SNAI2, SOX10, TYR, TYRP1 (Table 1) 9-19

X-linked, autosomal dominant, autosomal recessive

2-4/10,000 4 to 20/10,000 6

Major clinical symptoms 1, 2, 3:

  • Impaired social interaction
  • Impaired communication
  • Repetitive and stereotypic behaviors

Additional symptoms1, 2, 3:

  • Hyper- and hyposensitivity to sound and touch
  • Stereotypic behavior around food and their presentation
  • Abnormal sleep pattern (>60%)
  • Seizures (>25%)
  • Tantrums and/or self-injurious and aggressive behaviors
  • Impaired motor development with toe walking, hypotonia, general clumsiness
  • Catatonia syndrome (>15%)
  • Obesity
  • Presence of the specific behavioral changes and other autism-associated clinical feature
  • Positive family history of autism
  • Identification of a pathogenic variant in one of the associated genes (Table 1)

There is no cure for autism, however many symptomatic treatments can relieve symptoms1, 2, 3:

  • Psychosocial therapies, psychotherapy, cognitive behavioral psychotherapy, social skill interventions
  • Pharmacological treatments, including atypical antipsychotics, antidepressants, mood stabilizers
  • Supplements including vitamins, minerals, Omega-3 Fatty acids and others
  • Ongoing clinical trials investigating potential therapeutic effects of new drugs 
  • Developmental delay (global, language, intellectual or motor delay)
  • Intellectual disability
  • Attention deficit hyperactivity disorder
  • Mood disorders (anxiety disorder, obsessive compulsive disorder) or psychoses
  • Rett syndrome
  • Epileptic encephalopathy
  • Chromosomal abnormalities-associated syndromes (Angelman syndrome, trisomy 22)

To confirm/establish the diagnosis, CENTOGENE offers the following tests:

  • Syndromic autism NGS Panel which includes sequencing of the genes ADNP, ADSL, ALDH5A1, AMT, ANKRD11, ARID1B, BRAF, CACNA1C, CDKL5, CHD2, CHD7, CNTNAP2, CREBBP, DHCR7, EHMT1, FOXG1, FOXP1, GRIP1, HDAC8, HOXA1, HPRT1, MAGEL2, MECP2, MED12, MID1, NHS, NIPBL, NRXN1, NSD1, PCDH19, POGZ, PQBP1, PTEN, PTPN11, RAD21, RAI1, SCN1A, SCN2A, SETD2, SLC6A1, SLC6A8, SMC1A, SMC3, TBL1XR1, TCF4, TSC1, TSC2, UBE3A, VPS13B, ZEB2
  • Syndromic autism NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data
  • Individuals with a positive family history of syndromic autism
  • Individuals with most common symptoms of syndromic autism (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of syndromic autism can allow for genetic counseling and may direct medical management.

Table 1. Overview of the genes in Syndromic autism panel:

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ADNP 611386 Helsmoortel-van der Aa syndrome AD 11
ADSL 608222 Adenylosuccinase deficiency AR 10
ALDH5A1 610045 Succinic semialdehyde dehydrogenase deficiency AR 3
AMT 238310 glycine encephalopathy AR 9
ANKRD11 611192 KBG syndrome AD 25
ARID1B 614556 Coffin-Siris syndrome 1 AD 56
BRAF 164757 Cardiofaciocutaneous Syndrome 1; Lung Cancer; Noonan syndrome 7; LEOPARD syndrome 3 AD 18
CACNA1C 114205 long QT syndrome 8; Brugada syndrome 3 AD 30
CDKL5 300203 early infantile epileptic encephalopathy 2 XLD 19
CHD2 602119 childhood-onset epileptic encephalopathy AD 6
CHD7 608892 CHARGE syndrome; hypogonadotropic hypogonadism-5 with or without anosmia AD 92
CNTNAP2 604569 Pitt-Hopkins like syndrome 1; Autism susceptibility 15 AR 31
CREBBP 600140 Rubinstein-Taybi syndrome 1 AD 32
DHCR7 602858 Smith-Lemli-Opitz syndrome AR 10
EHMT1 607001 Kleefstra syndrome AD 16
FOXG1 164874 Rett syndrome, congenital variant AD 16
FOXP1 605515 Mental retardation with language impairment and with or without autistic features AD 10
GRIP1 604597 AR 2
HDAC8 300269 Cornelia de Lange syndrome 5 XLD 7
HOXA1 142955 Bosley-Salih-Alorainy syndrome 2
HPRT1 308000 Lesch-Nyhan syndrome; Kelley-Seegmiller syndrome XLR 9
MAGEL2 605283 Schaaf-Yang syndrome AD 8
MECP2 300005 MENTAL RETARDATION, X-LINKED 13; Autism susceptibility, X-linked 3; severe neonatal encephalopathy; Rett syndrome XL, XLD, XLR 18
MED12 300188 Opitz-Kaveggia syndrome /FG syndrome-1; Lujan-Fryns syndrome XLR 21
MID1 300552 Opitz GBBB syndrome, X-linked XLR 6
NHS 300457 Nance-Horan syndrome XL, XLD 8
NIPBL 608667 Cornelia de Lange syndrome 1 AD 40
NRXN1 600565 Pitt-Hopkins-like syndrome 2 AR 42
NSD1 606681 Sotos syndrome 1; acute myeloid leukemia AD 31
PCDH19 300460 early infantile epileptic encephalopathy type 9 XL 14
POGZ 614787 White-Sutton syndrome AD 8
PQBP1 300463 Renpenning Syndrome 1 XLR 2
PTEN 601728 Cowden syndrome 1; Prostate Cancer; Macrocephaly/autism syndrome; Meningioma, familial, susceptibility to AD 22
PTPN11 176876 LEOPARD syndrome 1; Noonan syndrome 1; Leukemia, juvenile myelomonocytic AD 12
RAD21 606462 Cornelia de Lange syndrome type 4 AD, AR 12
RAI1 607642 Smith-Magenis syndrome AD 9
SCN1A 182389 generalized epilepsy with febrile seizures plus 2; early infantile epileptic encephalopathy 6; familial hemiplegic migraine-3 AD 132
SCN2A 182390 benign familial neonatal-infantile seizures type 3; early infantile epileptic encephalopathy 11 AD 61
SETD2 612778 Luscan-Lumish syndrome AD 10
SLC6A1 137165 Myoclonic-atonic epilepsy AD 3
SLC6A8 300036 Cerebral creatine deficiency syndrome type 1 XLR 20
SMC1A 300040 Cornelia de Lange syndrome 2 XLD 10
SMC3 606062 Cornelia de Lange syndrome 3 AD 27
TBL1XR1 608628 Pierpont syndrome; Mental retardation, autosomal dominant 41 AD 2
TCF4 602272 Pitt-Hopkins syndrome AD 36
TSC1 605284 tuberous sclerosis type 1 AD 72
TSC2 191092 tuberous sclerosis-2 AD 156
UBE3A 601623 Angelman syndrome AD 22
VPS13B 607817 Cohen syndrome AR 26
ZEB2 605802 Mowat-Wilson syndrome AD 39