Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.3 Intellectual Disability

Table 31.3-4 Syndromes with Intellectual Disability and Behavioral Phenotypes ( continued )

Disorder

Pathophysiology

Clinical Features and Behavioral Phenotype

Tuberous sclerosis complex 1 and 2

Benign tumors (hamartomas) and malformations (hamartias) of central nervous system (CNS), skin, kidney, heart; dominant; 1/10,000 births; 50% TSC 1, 9q34; 50% TSC 2, 16p13 1/2,500–1/4,000; male = female; autosomal dominant; 50% new mutations; more than 90% paternal NF1 allele mutated; NFl gene 17q11.2; gene product is neurofibromin thought to be tumor suppressor gene Defect in hypoxanthine guanine phosphoribosyl-transferase with accumulation of uric acid; Xq26–27; recessive; rare (1/10,000–1/38,000) Defect in galactose-1-phosphate uridyltransferase or galactokinase or empiramase; autosomal recessive; 1/62,000 births in the U.S. Defect in phenylalanine hydroxylase (PAH) or cofactor (biopterin) with accumulation of phenylalanine; approximately 1/11,500 births; varies with geographical location; gene for PAH, 12q22–24.1; autosomal recessive

Epilepsy, autism, hyperactivity, impulsivity, aggression; spectrum of intellectual disability from none (30%) to profound; self-injurious behaviors, sleep disturbances

Neurofibromatosis type 1 (NF1)

Variable manifestations; café au lait spots, cutaneous neurofibromas, Lisch nodules; short stature and macrocephaly in 30–45 Half with speech and language difficulties; 10% with moderate to profound intellectual disability; verbal IQ > performance IQ; distractible, impulsive, hyperactive, anxious; possibly associated with increased incidence of mood and anxiety disorders Ataxia, chorea, kidney failure, gout Often severe self-biting behavior; aggression; anxiety; mild to moderate intellectual disability Vomiting in early infancy, jaundice, hepatosplenomegaly; later cataracts, weight loss, food refusal, increased intracranial pressure and increased risk for sepsis, ovarian failure, failure to thrive, renal tubular damage Possible intellectual disability even with treatment, visuospatial deficits, language disorders, reports of increased behavioral problems, anxiety, social withdrawal, and shyness Symptoms absent neonatally, later development of seizures (25% generalized), fair skin, blue eyes, blond hair, rash Untreated: mild to profound intellectual disability, language delay, destructiveness, self-injury, hyperactivity Early onset; short stature, hepatosplenomegaly; hirsutism, corneal clouding, death before age 10 years, dwarfism, coarse facial features, recurrent respiratory infections Moderate-to-severe intellectual disability, anxious, fearful, rarely aggressive Normal infancy; symptom onset at age 2–4 years; typical coarse faces with flat nasal bridge, flaring nostrils; hearing loss, ataxia, hernia common; enlarged liver and spleen, joint stiffness, recurrent infections, growth retardation, cardiovascular abnormality Hyperactivity, intellectual disability by 2 years; speech delay; loss of speech at 8–10 years; restless, aggressive, inattentive, sleep abnormalities; apathetic, sedentary with disease progression Microcephaly, short stature, midface hypoplasia, short palpebral fissure, thin upper lip, retrognathia in infancy, micrognathia in adolescence, hypoplastic long or smooth philtrum Mild to moderate intellectual disability, irritability, inattention, memory impairment

Lesch-Nyhan syndrome

Galactosemia

Phenylketonuria

Hurler’s syndrome 1/100,000; deficiency in a -L- iduronidase activity; autosomal recessive

Hunter’s syndrome 1/100,000, X-linked recessive; iduronate sulfatase deficiency; X q28

Fetal alcohol syndrome

Maternal alcohol consumption (trimester lll > ll > l); 1/3,000 live births in Western countries; 1/300 with fetal alcohol effects

(Table by B. H. King, M.D., R. M. Hodapp, Ph.D., and E. M. Dykens, Ph.D.)

Children with profound intellectual disability require con- stant supervision and are severely limited in both communication and motor skills. By adulthood, some speech development may be present, and simple self-help skills may be acquired. Clinical features frequently observed in populations with intellectual dis- ability either in isolation or as part of a mental disorder, include hyperactivity, low frustration tolerance, aggression, affective insta- bility, repetitive and stereotypic motor behaviors, and self-injuri- ous behaviors. Self-injurious behaviors occur more frequently and with greater intensity in more severe intellectual disability.

Dylan was a full-term infant, the second child born to his 42-year-old mother, a medical technician, and 48-year-old father, a high school basketball coach. The pregnancy was unremarkable, and Dylan’s sister, who was two years older, was healthy and devel- oping normally. The family lived in a rural town in the Midwest. Dylan was an extremely fussy, active newborn with extended peri- ods of crying that the pediatrician labeled classic colic. As a newborn, it was noticed that Dylan seemed to have large ears and strabismus, which the pediatrician said would probably resolve spontaneously. At