Speech disorders 3 By: Majid Mojarrad

Angelman syndrome 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

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

Happy phenotype Happy Excited Active Short attention span “Happy Puppet” syndrome

Consistent cardinal features 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

Other signs Seizure Abnormal EEG Strabismus Wide mouth Widely spaced teeth Frequent drooling Swallowing disorder Feeding problems during infancy Hypopigmented skin Light hair and eye color,

Prader-Willi syndrome 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

CLINICAL FEATURES 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)

Mild dysmorphic 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

Del(22q11.2) Syndromes relatively common genetic disorder 1 in 4000 live births Variable phenotype velocardiofacial syndrome DiGeorge syndrome Takao syndrome Cayler craniofacial syndrome

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

Fragile X syndrome 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

Typical facial features Long face Prominent forehead Prominent/long ears Prominent jaw

CNS involvement Delayed developmental milestones Mild to severe mental retardation Difficulty with: abstract thinking Sequential processing Mathematics short-term memory visual motor coordination Seizures

Connective tissue dysplasia 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

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

Goldenhar syndrome 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

Clinical features Can be bilateral or unilateral Hemifacial microsomia Ocular manifestations Unilateral microphthalmia Strabismus Optic nerve hypoplasia Macular hypoplasia Microphthalmia Anophthalmia

Ear anomalies Vertebral defects 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

Lowe syndrome 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%

Eye abnormalities Congenital cataracts (the hallmark of the disease) Developed prenatally Always present prior to birth Congenital glaucoma Microphthalmos Nystagmus Decreased visual acuity (blindness)

CNS (prominently involved organ) and behavioral abnormalities 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

Musculoskeletal abnormalities Secondary consequences of hypotonia, renal tubular acidosis, and/or hypophosphatemia Short stature Joint hypermobility Dislocated hips Scoliosis Kyphosis Fractures

STICKLER SYNDROME 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

Clinical features 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