Prader-Willi Syndrome

Behavioral Characteristics of Genetic Syndromes Christopher R. Milar, Ph.D.

ƒ Missing genetic material on chromosome 15 ƒ Inherited from the father ƒ Incidence: 1 in 12,000-15,000 live births ƒ Mild to Moderate Intellectual Disability (IQ in the 50-70 range)

PWS-Behavior ƒ Hyperphagia (98%) ƒ Temper Tantrums (88%) ƒ Obsessive Compulsive Behavior (71%) ƒ Self-injurious Behavior in the form of skin picking

ƒ Weakness in Sequential Processing ƒ Strengths in Simultaneous Processing

Angelman’s Syndrome ƒ Missing Genetic Material on Chromosome 15

ƒ Inherited from the Mother ƒ Genetic Defect is identical to Prader Willi Syndrome

ƒ Incidence: 1 in 10,000 to 12,000 live births ƒ Severe to Profound Intellectual Disability (IQ less than 30)

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Angelman’s Syndrome-Physical ƒ Large Mouth ƒ Ataxia and Jerky Arm Movements ƒ Mild to Moderate Cerebral Palsy ƒ Decreased Pigmentation of the Choroid and Iris

ƒ Maxillary Hypoplasia

Angelman’s Syndrome-Behavior ƒ Sleep Disturbance ƒ Inappropriate Laughter ƒ Happy Demeanor ƒ Seizure Disorder (often petit mal) ƒ Hyperactivity ƒ Pseudo-aggressive Behavior

William’s Syndrome ƒ Microdeletion on Chromosome 7 ƒ Incidence: 1 in 20,000 live births ƒ Mild to Moderate Intellectual Disability

William’s Syndrome-Physical ƒ Characteristic “Elfin” facie ƒ Cardio-vascular Abnormalities ƒ Prominent Lips ƒ Hoarse Voice ƒ Hypotonia Early and Hypertonia Later

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William’s Syndrome-Behavior ƒ Poor Visual Spatial Abilities ƒ Hypersensitivity to Sound (98%) ƒ Well Developed Expressive Language ƒ Attention Problems and Distractibility ƒ Anticipatory Anxiety ƒ Affinity for Music ƒ Perfect Pitch (estimate 30%)

William’s Syndrome-Behavior ƒ Hypersensitivity to Sound (98%) ƒ Poor Visual Spatial Abilities ƒ Well Developed Expressive Language ƒ Attention Problems and Distractibility ƒ Anticipatory Anxiety ƒ Affinity for Music ƒ Perfect Pitch (estimate 30%) ƒ Outgoing, Overly Friendly Personality

ƒ Absolute pitch ("AP"), widely referred to as perfect pitch, refers to the ability to identify a note by name without the benefit of a reference note, or to be able to produce a note (as in singing) that is the correct pitch without reference.

Fragile X Syndrome ƒ Defect on X Chromosome ƒ Incidence: 1 in 3000 live births ƒ Leading Genetic Cause of Intellectual Disability ƒ Variable Level of Intellectual Disability

Fragile X Syndrome-Physical ƒ Prominent Ears ƒ Long, Triangular Face ƒ Hyperextensible Finger Joints ƒ High, Arched Palate ƒ Macro-orchidism

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Fragile X Syndrome-Behavior ƒ Gaze Aversion (different from autism) ƒ Self-Injurious Behavior (hand biting) ƒ Hyperarousal ƒ Hypersensitivity ƒ Temper Tantrums ƒ Perseveration ƒ ADHD

Fragile X Syndrome-Behavior

ƒ Language Abnormalities including: ƒ Mumbling ƒ Echolalia ƒ Cluttered Speech

Fragile X Syndrome-Behavior ƒ Cluttering (also called tachyphemia) is a communicative disorder characterized by speech that is difficult for listeners to understand due to rapid speaking rate, erratic rhythm, poor syntax or grammar, and words or groups of words unrelated to the sentence.

ƒ Language Abnormalities including: ƒ Mumbling ƒ Echolalia ƒ Cluttered Speech ƒ Self Talk

Cornelia de Lange Syndrome ƒ exact cause is not known, possibly a gene located on chromosome 3 (3q26.3)

ƒ duplication of chromosome 3q26-27 yields a similar phenotype ƒ Incidence: 1:10,000 to 1:100,000 (most accurate study showed 1:50,000) ƒ Severe to Profound Intellectual Disability most common

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Cornelia de Lange SyndromePhysical ƒ Short Stature ƒ Bushy Eyebrows ƒ Small Nose, Anteverted Nostrils ƒ Hirsutism ƒ Characteristic Lips and Mouth ƒ Thin lips ƒ Midline beak of upper lip and notch in lower lip ƒ Downward, curving angle of mouth

Cornelia de Lange Syndrome Behavior ƒ Self-Injurious Behavior (82%)-Multiple Sites ƒ Sleep Disturbance (55%) ƒ Hyperactivity (74%) ƒ Aggression (49%)

Rett Syndrome ƒ Mutated Gene on X Chromosome ƒ Occurs only in Females (?) ƒ Incidence: 1 in 10,000 to 15,000 live births ƒ Severe to Profound Intellectual Disability

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Rett Syndrome-Physical ƒ Normal Early Development ƒ Subsequent Loss of Acquired Skills ƒ ƒ ƒ ƒ ƒ ƒ

ƒ Hand Use ƒ Communication

Deceleration of Head Growth Gait Abnormalities Bruxism Aerophagia Megacolon Late Developing Dysphagia

Implications for Interventions ƒ Many gene based behaviors insensitive to manipulation of consequences: ƒ Hand Biting in Fragile X Syndrome ƒ Hand washing in Rett Syndrome ƒ Hyperphagia, OCD, and SIB in Prader-Willi Syndrome ƒ SIB in Cornelia de Lange Syndrome ƒ Pseudo-aggression in Angelman’s Syndrome

Implications for Interventions ƒ Many gene based behaviors are resistant to pharmacological interventions: ƒ Sleep disturbance in Angelman’s and Cornelia de Lange Syndromes ƒ SIB in Fragile X and Cornelia de Lange Syndromes ƒ Hyperactivity in Angelman’s and Cornelia de Lange Syndromes

Rett Syndrome-Behavior ƒ Characteristic Hand Movements (100%) ƒ Self-Injury (50%) ƒ Hyperactivity ƒ Anxiety (75%) characterized by ƒ Hyperventilation ƒ Screaming ƒ Distress

Implications for Interventions ƒ Some gene based behaviors can be effectively treated by preventative approaches: ƒ Anticipatory Anxiety in Williams Syndrome ƒ Aggression in Cornelia de Lange Syndrome ƒ Tantrums in Fragile X Syndrome

Implications for Interventions ƒ Some gene based behaviors do respond to pharmacological interventions: ƒ ADHD symptoms in Fragile X Syndrome ƒ OCD symptoms in Prader Willi Syndrome ƒ SIB in Prader Willi Syndrome (?)

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