Neurodevelopmental disorders

Neurodevelopmental disorders are a class of psychiatric disorders characterized by childhood-onset, potentially lifelong deficits resulting in the impairment of personal, social, academic, and occupational function. The specific causes of neurodevelopmental disorders are unknown but assumed to be multifactorial, with certain associations having been established (e.g., fragile X syndrome, tuberous sclerosis, Rett syndrome, epilepsy, low birth weight).

Intellectual disability is characterized by impaired mental abilities (e.g., abstract thinking, academic learning, problem solving) that cause impairments in adaptive functioning (e.g., communication, independent living). Global developmental delay is defined as a significant delay in ≥ 2 of the major developmental domains (gross motor, fine motor, language, cognition, and social milestones) in children < 5 years of age. Specific learning disorders are characterized by persistent impairment in a specific function, i.e., reading, written expression, or maths. The disorder typically manifests in the first few years of schooling and results in poor academic performance in the corresponding discipline. Language disorders and speech sound disorders are characterized by deficits in the acquisition and/or comprehension of language, speech, and communication. Childhood-onset fluency disorder (stuttering) is characterized by disturbances in the normal fluency of speech that manifests with sound and syllable repetition, sound prolongation, and broken words.

Other neurodevelopmental disorders, including autism spectrum disorder and attention deficit hyperactivity disorder, are discussed in separate articles.

For information regarding neurodevelopmental motor disorders, including stereotypical movement disorder, and tic disorders (Tourette syndrome, persistent motor tic disorders, persistent vocal tic disorder, and sporadic transient tic disorder), see “Tourette syndrome.”

• Definition: a neurodevelopmental disorder that manifests during the developmental period ; and affects an individual's intellectual abilities (e.g., abstractive thinking, language, memory) and adaptive functioning (e.g., communication, independent living).
• Prevalence: ∼ 1% in the general population ^[1]
• Etiology
  • Congenital
    • Genetic conditions (e.g., fragile X syndrome, trisomy 21, Klinefelter syndrome)
    • Exposure to teratogens in utero (e.g., fetal alcohol syndrome)
    • Congenital hypothyroidism
    • Congenital infections (e.g., toxoplasmosis, rubella)
    • Perinatal hypoxia
    • Perinatal trauma
  • Acquired
    • CNS infections (e.g., viral encephalitis, meningitis)
    • CNS malignancies (e.g., neuroblastoma)
    • Traumatic brain injury
    • Intoxications (e.g., lead, mercury)
    • Iodine deficiency
    • Malnutrition
• Clinical features
  • The following features should be present:
    • Deficits in cognitive functioning such as learning, problem-solving, reasoning, abstract thinking, judgment, and planning
    • Impaired adaptive functioning (e.g., inability to maintain personal independence and social responsibility) leading to educational, occupational, communication, and social problems
    • Onset during the developmental period (during childhood or adolescence)
  • Other features include:
    • Features of accompanying mental conditions (e.g., apathy and depressed mood in depression, poor attention in ADHD)
    • Features of the causative conditions (e.g., characteristic appearance in trisomy 21, behavioral problems in Lesch-Nyhan syndrome)
• Diagnostics
  • Intelligence quotient (IQ) testing
  • Workup for identification of underlying disease (e.g., genetic testing, neuroimaging)
• Management
  • Nonpharmacological
    • Psychotherapy (e.g., cognitive-behavioral therapy, family-oriented therapy)
    • Occupational therapy
    • Special education programs
    • Speech-language therapy
  • Pharmacological: used to control psychiatric symptoms of accompanying conditions
    • Atypical antipsychotics (e.g., risperidone, aripiprazole, olanzapine) ^[2]
    • Antidepressants (e.g., SSRIs)

References: ^[1][3][4]

• Definition: significant delay in ≥ 2 of the major developmental domains (gross motor, fine motor, language, cognition, and social milestones) in children < 5 years of age
• Prevalence: up to 5% of children in developed countries
• Etiology
  • Chromosomal abnormalities (e.g., trisomy 13, trisomy 18, trisomy 21, Turner syndrome, Klinefelter syndrome)
  • Metabolic disorders (e.g., phenylketonuria, lysosomal storage diseases, maple syrup urine disease)
  • Infections (e.g., TORCH, herpes simplex, meningitis)
  • Intrauterine exposure to toxic substances/drugs (e.g., alcohol, phenytoin, valproate)
  • Birth complications (e.g., preeclampsia, multiparity)
  • Prematurity
  • Untreated neonatal jaundice
  • Undernutrition, neglect
  • Heavy metal poisoning (lead, mercury)
  • Severe head injuries, intracranial bleeds
  • Cerebral palsy (associated with prematurity, SGA, and perinatal asphyxia)
• Clinical features
  • Mild forms may not be detected until preschool age
  • Severe delay in meeting milestones (see “Developmental milestones” for details) in ≥ 2 of the major developmental domains (gross motor, fine motor, language, cognition, and social milestones) < 5 years of age
  • Commonly associated with behavioral abnormalities (e.g., ADHD, autism spectrum disorders, bipolar disorders)
• Diagnostics of global developmental delay
  • Screening for developmental and intelligence quotient
  • Detailed history, physical examination, and assessment of milestones and primitive reflexes
  • MRI of the brain: to identify CNS malformation, intracranial bleeding, or hydrocephalus
  • Genetic testing: if chromosomal anomalies are suspected
  • Screening for infections (e.g., TORCH, HIV): in children with failure to thrive, cranial/cerebral malformations or intracranial calcifications
  • Serum and urine analysis and enzyme studies: In infants suspected of having a metabolic disorder
• Management
  • Treatment of the underlying cause (if reversible)
  • Early intervention to minimize the severity of disability
  • Multidisciplinary team: neurologists, orthopedics, physical therapists, speech therapists, nutrition
  • Special schooling and occupational therapy

References:^[5][6]

• Definition
  • A neurodevelopmental disorder that occurs due to a combination of genetic, epigenetic, and environmental factors and results in difficulties learning and applying specific academic skills
  • Features should be present for more than 6 months despite academic interventions to address these problems.
• Prevalence: 5–15% in the school-age population ^[3]
• Clinical features
  • Inability to acquire age-appropriate academic skills, such as reading (most common), spelling, writing, operations with numbers,or mathematical reasoning
    • Dyslexia: a specific learning disability characterized by difficulties with word recognition and decoding, as well as spelling, which often results in below-average reading comprehension, limited vocabulary, and delayed language development that cannot be attributed to intellectual disability (IQ < 70)
    • Dyscalculia: a specific learning disability with impairment in mathematics. It is characterized by problems processing numerical information, learning arithmetic facts, and performing accurate or fluent calculations that can not be attributed to intellectual disability (IQ < 70)
  • General cognitive abilities (e.g., reasoning, abstract thinking) are normal (in contrast to intellectual disability)
• Management
  • Academic support (e.g., individualized learning programs)
  • Regular school psychology consultations
  • Individual or family psychotherapy
  • Extracurricular activities to improve academic and social inclusion

References: ^[3]

• Definition: : A condition characterized by disturbances in the normal fluency of speech with onset in the early developmental period.
• Prevalence: 5–10% of preschool children ^[7]
• Clinical features
  • Onset of symptoms typically between age 2–7 years
  • Sound and syllable repetition
  • Sound prolongation of letters
  • Repetition of monosyllabic words
  • Broken words and speech blocking
  • Substitution of words to avoid problematic words
  • Secondary maladaptive behavior (e.g., word avoidance, mannerisms, avoidance of speaking) may develop in some patients
• Diagnostic criteria (DSM-5)
  • Persistent disturbances in the normal fluency of speech
  • Stuttering results in anxiety related to speaking, impaired social participation, and/or poor academic performance in childhood
  • Not attributable to sensory impairment or speech-motor deficit, or other medical condition (e.g., stroke, CNS trauma)
• Management ^[7]
  • Spontaneous resolution in 65–85% of preschool children with disfluency by the age of 7 years
  • Speech therapy for severe or persistent cases
    • Develop compensatory techniques to improve fluency
    • Treat maladaptive behavior

• Definition: A communication disorder characterized by a delayed and/or impaired ability to comprehend and/or produce language.
• Classification
  • Expressive language delay
    • Characterized by an inability to formulate language (e.g., spoken, written, signed language)
    • Manifestations include word-finding difficulty, omission of words within sentences, and use of incorrect tenses.
  • Receptive language delay
    • Characterized by an inability to understand and process language (e.g., spoken, written, signed language)
    • Manifestations include impaired ability to understand and follow directions, misunderstanding the words and meanings of stories or information
• Diagnostic criteria (according to DSM-V) ^[3]
  • Persistently reduced ability to learn, understand, and use language (written, spoken, and/or signed), characterized by limited vocabulary for age, incorrect understanding of word meanings, difficulty with sentence structure, and/or incorrect grammar use
  • A significant deviation of language abilities below those expected for age, resulting in impaired communication, social participation, and/or poor academic performance
  • The language difficulties begin to manifest during the early developmental period.
  • The symptoms are not due to another condition (e.g., hearing impairment, intellectual disability, cerebral palsy).
• Differential diagnosis ^[8]
  • Normal variations in language acquisition (especially in children < 4 years of age)
  • Specific learning disorders, e.g., dyslexia
  • Autism spectrum disorder
  • Intellectual disability
  • Hearing impairment
  • Child neglect and abuse
• Management: : language therapy

• Definition: a communication disorder characterized by persistent difficulties in phonology and/or articulation .
• Diagnostic criteria (according to DSM-V) ^[3]
  • Impaired verbal communication and speech intelligibility due to persistent difficulty in speech sound production.
  • The communication difficulties cause impaired social participation and/or poor academic performance in childhood.
  • The speech difficulties begin during the early developmental period.
  • The symptoms are not due to an underlying condition (e.g., hearing impairment, cleft palate, cerebral palsy).
• Differential diagnosis ^[9]
  • Normal variations in speech (e.g., speech delay in children learning two languages)
  • Expressive language disorder (often occurs with speech sound disorder)
  • Hearing impairment
  • Selective mutism
  • Motor/neurological disorders (e.g., apraxia, dysarthria due to cerebral palsy)
  • Structural abnormalities (e.g., cleft palate)
• Management: : speech therapy for articulation and/or phonological techniques