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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Pediatrics · ADNP Syndrome

Symptoms, Development, & Early Signs of ADNP Syndrome

At a Glance

ADNP syndrome is a multi-system genetic condition marked by global developmental delays, severe speech challenges, and unique autism-like behaviors. A highly distinct early sign is premature teething, with babies often getting their first teeth before 3 to 4 months of age.

While every child with ADNP syndrome is an individual, many parents find a sense of clarity when they see their child’s unique traits reflected in the clinical descriptions of the syndrome. ADNP syndrome is a multi-system condition, meaning it affects many different parts of the body and stages of development [1][2].

The Neurodevelopmental Landscape

The most consistent features of ADNP syndrome involve how the brain and body develop and communicate.

  • Global Developmental Delay (GDD): Children typically reach milestones later than their peers. This is often first noticed as hypotonia (low muscle tone), which can make a baby feel “floppy” and delay milestones like rolling over, sitting up, and walking [3][1]. It is common for children with ADNP to begin walking much later, sometimes after age 3 [4][5].
  • Speech and Communication Challenges: Speech is often significantly affected. Many children remain non-verbal for several years or use word approximations, sign language, and Augmentative and Alternative Communication (AAC) devices to communicate [4][6]. Even into adulthood, many individuals may function developmentally at a level younger than 3 years old in some areas [7][8].
  • Intellectual Disability: Most children will have some degree of intellectual disability, though the range of ability varies widely depending on the specific genetic mutation [3][9].

A Unique Clinical Marker: Early Teething

One of the most distinctive “clues” for ADNP syndrome is premature primary tooth eruption [10]. While most babies get their first tooth between 6 and 10 months, many children with ADNP syndrome begin teething much earlier—often before 3 or 4 months of age [10][11]. Some children may even have a nearly full set of teeth by their first birthday [10]. This early teething is so specific to ADNP syndrome that researchers consider it a vital diagnostic sign [10].

The “ADNP Personality” and Autism

The relationship between ADNP syndrome and Autism Spectrum Disorder (ASD) is unique. While many children meet the diagnostic criteria for autism, their social behavior often looks different than “typical” autism [1][12]:

  • “Sweet and Sassy”: Many parents and clinicians describe children with ADNP as having a notably “happy,” “sweet,” or “social-seeking” temperament [12][1]. They may be very friendly and eager to interact with adults.
  • Social Impairment: Despite being social, children often struggle with the nuances of social interaction, which can be linked to the severity of their speech delays [6].
  • Sensory Reactivity: It is common for children to have unusual responses to sensory input, such as a high pain tolerance or sensitivities to certain sounds and textures [9][13].

Common Systemic Signs

Because the ADNP gene is active throughout the body, you may notice symptoms in other systems:

  • Vision: Issues like strabismus (crossed eyes) or ptosis (drooping eyelids) are very common [2][14].
  • Gastrointestinal: Chronic constipation or significant changes in gut health are frequently reported [15][1].
  • Cardiac: Some children are born with congenital heart defects (such as small holes in the heart) that may require monitoring [2][14].
  • Facial Features: Many children share similar facial characteristics, such as a prominent forehead, a thin upper lip, or widely spaced eyes [16][1].

Recognizing these patterns is not about placing limits on your child, but about understanding the “why” behind their unique journey and ensuring they get the right support for every system of their body.

For more information on navigating these medical challenges, visit the Multisystem Management & Building Your Care Team page.

Common questions in this guide

Is early teething a sign of ADNP syndrome?
Yes, premature primary tooth eruption is a distinct diagnostic clue for ADNP syndrome. Babies with this condition often begin teething before 3 or 4 months of age and may have a nearly full set of teeth by their first birthday.
What is the 'ADNP personality' and how does it relate to autism?
Children with ADNP syndrome often have a happy, sweet, and social-seeking temperament, which differs from typical autism presentations. However, despite being eager to interact, they still experience significant challenges with social nuances and communication.
Will my child with ADNP syndrome be able to speak?
Speech delays are typically significant in ADNP syndrome. Many children remain non-verbal for years and rely on sign language, word approximations, or Augmentative and Alternative Communication (AAC) devices to express their needs.
What other physical symptoms are caused by ADNP syndrome?
ADNP is a multi-system condition that can cause low muscle tone, vision issues like crossed eyes or drooping eyelids, chronic constipation, and sometimes congenital heart defects. It also creates distinct facial features such as a prominent forehead.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How does my child's current level of hypotonia affect their ability to reach gross motor milestones like sitting or walking?
  2. 2.Since speech delays are often significant in ADNP syndrome, can we begin evaluations for alternative communication (AAC) devices now?
  3. 3.Based on my child's specific ADNP mutation, are there common sensory processing patterns we should be aware of?
  4. 4.Can you explain how my child's 'happy' temperament might influence their autism assessment and the types of behavioral support they receive?
  5. 5.Does my child's early teething mean we should have an earlier or more frequent schedule for pediatric dental exams?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (16)
  1. 1

    Clinical impact and in vitro characterization of ADNP variants in pediatric patients.

    Ge C, Tian Y, Hu C, et al.

    Molecular autism 2024; (15(1)):5 doi:10.1186/s13229-024-00584-7.

    PMID: 38254177
  2. 2

    Helsmoortel-van der Aa syndrome in a Chinese pediatric patient due to ADNP nonsense mutation: A case report.

    Chen LJ, You ZM, Chen WH, et al.

    Frontiers in pediatrics 2023; (11()):1122513 doi:10.3389/fped.2023.1122513.

    PMID: 37063667
  3. 3

    Abnormal fetal ultrasound leading to the diagnosis of ADNP syndrome.

    Rosenblum J, Van der Veeken L, Aertsen M, et al.

    European journal of medical genetics 2023; (66(11)):104855 doi:10.1016/j.ejmg.2023.104855.

    PMID: 37758165
  4. 4

    The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings.

    Gozes I, Patterson MC, Van Dijck A, et al.

    Frontiers in endocrinology 2017; (8()):107 doi:10.3389/fendo.2017.00107.

    PMID: 28579975
  5. 5

    Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP.

    Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, et al.

    Biological psychiatry 2019; (85(4)):287-297 doi:10.1016/j.biopsych.2018.02.1173.

    PMID: 29724491
  6. 6

    The autism spectrum phenotype in ADNP syndrome.

    Arnett AB, Rhoads CL, Hoekzema K, et al.

    Autism research : official journal of the International Society for Autism Research 2018; (11(9)):1300-1310 doi:10.1002/aur.1980.

    PMID: 30107084
  7. 7

    Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living.

    Levine J, Hakim F, Kooy RF, Gozes I

    Journal of molecular neuroscience : MN 2022; (72(8)):1531-1546 doi:10.1007/s12031-022-02048-0.

    PMID: 35920977
  8. 8

    Longitudinal Genotype-Phenotype (Vineland Questionnaire) Characterization of 15 ADNP Syndrome Cases Highlights Mutated Protein Length and Structural Characteristics Correlation with Communicative Abilities Accentuated in Males.

    Levine J, Lobyntseva A, Shazman S, et al.

    Journal of molecular neuroscience : MN 2024; (74(1)):15 doi:10.1007/s12031-024-02189-4.

    PMID: 38282129
  9. 9

    Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis.

    Siper PM, Layton C, Levy T, et al.

    Genes 2021; (12(3)) doi:10.3390/genes12030351.

    PMID: 33673501
  10. 10

    Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children.

    Gozes I, Van Dijck A, Hacohen-Kleiman G, et al.

    Translational psychiatry 2017; (7(7)):e1166 doi:10.1038/tp.2017.128.

    PMID: 28675391
  11. 11

    Interaction between FMDV Lpro and transcription factor ADNP is required for optimal viral replication.

    Medina GN, Knudsen GM, Greninger AL, et al.

    Virology 2017; (505()):12-22 doi:10.1016/j.virol.2017.02.010.

    PMID: 28219017
  12. 12

    From the Editors Desk: Angela Zawacki-Downing Writing to Professor Illana Gozes, Editor-in-Chief Journal of Molecular Neuroscience-Speaking from a Mother's Heart, AD's ADNP Syndrome.

    Zawacki-Downing A

    Journal of molecular neuroscience : MN 2019; (68(4)):511-514 doi:10.1007/s12031-019-01337-5.

    PMID: 31201656
  13. 13

    ADNP Exhibits Methyltransferase Activity in Overexpression Systems and Modulates DNA and Histone Methylation.

    D'Incal CP, Van Rossem KE, Cappuyns E, et al.

    Autism research : official journal of the International Society for Autism Research 2025; (18(11)):2174-2191 doi:10.1002/aur.70132.

    PMID: 41174994
  14. 14

    Helsmoortel-Van der Aa Syndrome as emerging clinical diagnosis in intellectually disabled children with autistic traits and ocular involvement.

    Pascolini G, Agolini E, Majore S, et al.

    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2018; (22(3)):552-557 doi:10.1016/j.ejpn.2018.01.024.

    PMID: 29475819
  15. 15

    Microbiota changes associated with ADNP deficiencies: rapid indicators for NAP (CP201) treatment of the ADNP syndrome and beyond.

    Kapitansky O, Giladi E, Jaljuli I, et al.

    Journal of neural transmission (Vienna, Austria : 1996) 2020; (127(2)):251-263 doi:10.1007/s00702-020-02155-5.

    PMID: 32072336
  16. 16

    Oro-Dental Manifestations in a Pediatric Patient Affected by Helsmoortel-Van der Aa Syndrome.

    Petruzzi M, Stella A, Capra V, et al.

    International journal of environmental research and public health 2021; (18(17)) doi:10.3390/ijerph18178957.

    PMID: 34501546

This page describes the common symptoms and developmental patterns of ADNP syndrome for educational purposes only. Always consult a pediatric geneticist or specialist for your child's specific medical evaluation and care.

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