By: Majid Mojarrad. incidence of 1/10,000 to 1/30,000 Deletion of maternal 15q11-13 Maternal Uniparental disomy of 15q11-13 Severe mental retardation.

Speech disorders 3By:

Majid Mojarrad

incidence of 1/10,000 to 1/30,000

Deletion of maternal 15q11-13

Maternal Uniparental disomy of 15q11-13

Severe mental retardation

Severe speech impairment

Delayed development by 6–12 months of age

Receptive language skills

Nonverbal communication

Angelman syndrome

balance disorder◦ unstable and jerky movements◦ gait ataxia◦ tremulous movements of the limbs

Happy Excited Active Short attention span “Happy Puppet” syndrome

Happy phenotype

Normal newborn phenotype

Developmental delay

◦ Starting around 6 months of age

◦ Eventually classified as severe developmental delay and/or mental retardation

◦ Profound speech impairment

◦ Absent or minimal use of words

◦ Receptive and nonverbal communication skills

Movement or balance disorder

◦ Abnormal ataxic gait

◦ Puppet-like jerky movements of limbs

◦ Hand flapping movement

Consistent cardinal features

Seizure

Abnormal EEG

Strabismus

Wide mouth

Widely spaced teeth

Frequent drooling

Swallowing disorder

Feeding problems during infancy

Hypopigmented skin

Light hair and eye color,

Other signs

Deletion of normally active paternally inherited genes at chromosome 15q11-q13

neurogenetic disorder characterized by:◦ Hypotonia◦ feeding difficulties in infancy

Followed by◦ Hyperphagia◦ Hypogonadism◦ mental retardation◦ Short stature

It was the first recognized microdeletion syndrome identified with high-resolution chromosome analysis

incidence of Prader-Willi syndrome is approximately 1/10,000 to 1/15,000 individuals

Prader-Willi syndrome

Neonatal presentation

◦ Central hypotonia in infancy

◦ Poor feeding/sucking

◦ Poor weight gain (failure to thrive)

◦ Genital hypoplasia/hypogonadism

◦ Diminished deep tendon reflexes

◦ Abnormal squeaky weak cry

◦ History of fetal inactivity (in utero hypotonia)

CLINICAL FEATURES

Developmental delay Mild dysmorphic features

◦ Almond-shaped eyes◦ Dolichocephaly◦ Narrow bifrontal diameter◦ Narrow nasal bridge◦ Small mandible◦ Small mouth◦ High-arched palate◦ Down-turned lips◦ Thick viscous saliva

Speech articulation defects

relatively common genetic disorder 1 in 4000 live births Variable phenotype

◦ velocardiofacial syndrome◦ DiGeorge syndrome◦ Takao syndrome◦ Cayler craniofacial syndrome

Del(22q11.2) Syndromes

congenital heart defects palate abnormalities aplasia or hypoplasia of the thymus small or absent parathyroid glands distinct facial features immune problems learning disabilities other abnormalities speech abnormalities congnitive difficulties

failure to thrive

feeding problems due to their palate abnormalities

Gastroesophageal reflux

vomiting problems

Generalized growth problems

Short stature

specific learning disabilities

developmental delay

higher rates of:◦ bipolar affective disorder◦ manic-depressive illness◦ Schizoaffective disorder◦ Depression◦ Mild mental retardation◦ attention deficit hyperactivity disorder

Martin-Bell syndrome Most common form of inherited mental retardation about one in 4,000 to one in 6,250 males Three nucleotide repeat expansion (CGG) developmental delay variable levels of mental retardation behavioral and emotional difficulties

Fragile X syndrome

Long face Prominent forehead Prominent/long ears Prominent jaw

Typical facial features

Delayed developmental milestones Mild to severe mental retardation Difficulty with:

◦ abstract thinking◦ Sequential processing◦ Mathematics◦ short-term memory◦ visual motor coordination

Seizures

CNS involvement

Hyperextensible finger joints Double-jointed thumbs Flat feet High-arched palate Mitral valve prolapse (55%, diagnosed by echocardiography) Dilatation of the ascending aorta Inguinal hernia Soft skin

Connective tissue dysplasia

Poor eye contact (excessive shyness) Attention-deficit/hyperactivity disorder Hyperactivity Speech disorder Echolalia Autism Autistic-like features Schizotypal personality disorder Anxiety disorder

Behavior abnormalities

congenital condition associated with abnormalities of the head

and the bones of the spinal column

one of every 3,000 to 5,000 live births

Males are affected more frequently than females

abnormalities are typically limited to the face and vertebrae

Goldenhar syndrome

Can be bilateral or unilateral

Hemifacial microsomia

Ocular manifestations

◦ Unilateral microphthalmia

◦ Strabismus

◦ Optic nerve hypoplasia

◦ Macular hypoplasia

◦ Microphthalmia

◦ Anophthalmia

Clinical features

Ear anomalies◦ Microtia◦ Preauricular tags and/or pits◦ Middle ear anomaly◦ Inner ear defects◦ Variable deafness

Vertebral defects◦ Hemivertebrae◦ Hypoplasia of vertebrae, usually cervical◦ Abnormal ribs◦ scoliosis

Craniofacial features◦ Cranial nerve palsy◦ Cleft lip/palate◦ Malfunction of soft palate◦ Decreased parotid secretion◦ Anomalies in function or structure of the tongue◦ Low scalp hair line

Rare X-linked recessive disorder (Xq26.1) Congenital cataracts mental retardation Generalized aminoaciduria New mutations in 31.6% of affected males Germline mosaicism in 4.5%

Lowe syndrome

Eye abnormalities◦ Congenital cataracts (the hallmark of the disease)

Developed prenatally Always present prior to birth

◦ Congenital glaucoma◦ Microphthalmos◦ Nystagmus◦ Decreased visual acuity (blindness)

Neonatal/infantile hypotonia Delay in motor milestones Cognitive impairment Areflexia by one year of age Mental retardation (common but not cardinal feature) Seizures Neuropathologic and neuroimaging abnormalities Self injury

CNS (prominently involved organ) and behavioral abnormalities

Secondary consequences of hypotonia, renal tubular acidosis,

and/or hypophosphatemia

◦ Short stature

◦ Joint hypermobility

◦ Dislocated hips

◦ Scoliosis

◦ Kyphosis

◦ Fractures

Musculoskeletal abnormalities

Progressive myopia, retinal detachment and blindness,

and premature degenerative changes in various joints

autosomal dominant with wide variation in expression

locus and allelic heterogeneity

COL2A1 gene mutations: Chr12q13.11-q13.2

STICKLER SYNDROME

Hearing impairment Normal intelligence Facial bone hypoplasia

◦ Flat midface◦ Depressed nasal bridge◦ Maxillary hypoplasia◦ Mandibular hypoplasia◦ High arched/cleft palate◦ Abnormal teeth

Joint hyperextensibility Enlarged joints

Clinical features

Long fingers Scoliosis Hip dislocation Relative muscle hypoplasia Premature osteoarthritis

Clinical features