Table 2. Complications of common genetic syndromes with intellectual disability in adulthood that are of significance for the primary care physician.

Syndrome	Genetic background/frequency	Organ(s) involved	Clinical manifestations	Tasks for the primary care physician
Down syndrome	Trisomy of chromosome 21 with various genetic variants: free trisomy (95%), translocational trisomy, mosaic trisomy 1/600 newborns	Thyroid	Hypothyroidism	Annual TSH checks
		Heart	Mitral/aortic valve disease, ASD, ASVD	Cardiac ultrasound, care by a cardiologist; risk of endocarditis!
		Blood	Acute myeloid leukemia (1/100)	If nonspecific symptoms are present, differential blood count
		Metabolism	Obesity	Proper nutrition and exercise
		Brain	Alzheimer dementia Gait disturbance Epilepsy (10%, especially myoclonic epilepsy)	Neurological consultation in case of a cognitive decline, behavioral change, or impairment of consciousness
		Skeleton	Atlantoaxial dislocation Hip dysplasia	Orthopedic examination, cervical spine x-ray
		Respiration	Sleep apnea	Polygraphy as indicated
		Sensory organs	Impaired hearing Visual disturbance (70%), cataract	Otological and/or ophthalmological consultation if there appears to be a disturbance (behavior!)
Fragile X syndrome	Trinucleotide expansion in the FRM1 gene (fragile X mental retardation 1) on the X chromosome Males: 1/1200 Females: 1/2500	Brain	Autism Behavioral disturbance ID Epilepsy (20%)	Psychiatric care Special needs education Neurologic care, EEG
		Skeleton	Scoliosis Ankle deformity	Orthopedic care / concomitant orthopedic care
		Heart	Mitral valve prolapse	Cardiologist, cardiac ultrasound
		Respiration	Sleep apnea	If symptomatic, polygraphy
Tuberous sclerosis (TS)	Autosomal dominant mutation in the TSC1 or TSC2 gene on chromosome 9q34 or 16q13, repsectively, causing overactivation of mTOR 1/5800; 60% new mutations	Brain	Tubers, developmental disorder, ID, epilepsy, tumors (giant-cell astrocytoma), hydrocephalus	Concomitant neurological careAnticonvulsants Periodic follow-up head CT or MRI (on an individual basis)
		Skin	Adenoma sebaceum	Concomitant dermatological care
		Kidneys	Angiomyolipoma	Renal ultrasound, abdominal MRI, GFR
		Lung	Lymphangioleiomyomatosis (interstitial lung disease)	Pulmonary function tests,chest CT as indicated
		Heart, skin, teeth, eyes	Non-cancerous tumors	Referral to a TS center (treatment with an mTOR inhibitor?)
MD-1 (myotonic dystrophy type 1, Curschmann–Steinert disease)	Autosomal-dominant trinucleotide expansion in the untranslated 3´ region of the dystrophia myotonica protein kinase (DMPK) gene onchromosome 19 1/10 000	Muscles	Progressive, mainly distal myotonia	Physiotherapy, physical aids
		Brain	Tetraparesis ID only with juvenile onset and in congenital forms Organic personality change	Concomitant psychiatric care as indicated Psychosocial assistance
		Respiration	Respiratory muscle paralysis Respiratory drive (80%)	Pulmonary function teststcCO 2 in sleep (inpatient sleep study), indication for non-invasive ventilation
		Pancreas	Diabetes mellitus (20%)	HbA1c, glucose
		Heart	RLS (arrhythmia, sudden cardiac death)	Concomitant care by a cardiologist Long-term ECG Check indication for pacemaker
		Sensory organs	Cataract, hearing impairment	Concomitant opthalmological care
Rett syndrome	Dominant mutation of the MECP2 gene on chromosome Xp28, 90% new mutations 1/10 000 in girls, very rare in boys	Brain	Severe, progressive developmental disorder, epilepsy, spasticity	Concomitant care by a neurologist (always) and a psychiatrist (in case of behavioral disturbances (epilepsy center)
		Skeleton	Scoliosis Microcephaly	Corset, positional aids, walking aids Pediatric (neuro-)orthopedic care
		Teeth	Bruxism with destruction of the teeth	Dentist, orthodontist
Deletion syndrome 22q11.2 (DiGeorge syndrome, velocardiofacial syndrome)	The most common chromosomal microdeletion (1/3000), generally due to a new mutation	Immune system	Immune deficiency	Primary care physician, immunologist
		Endocrine system	Hypoparathyroidism	Endocrinologist
		Heart	Congenital cardiac anomalies Aortic stenosis Multiple organ malformations	Cardiologist, cardiac surgeon, pediatric surgeon
		Mental health	ID, schizophrenic psychoses	Concomitant psychiatric treatment
Prader–Willi syndrome	Multiple mechanisms: 1. deletion 15q11q13 of paternal origin (70%) 2. maternal uniparental disomy (15%) 3. imprinting center defect: the corresponding genes on the paternal chromosome are turned off. Frequency: 1/10 000	Metabolism	Obesity, diabetes mellitus, metabolic synrome	Dietary counseling Diabetes therapy Behavioral therapy
		Endocrine system	Hypogonadism Short stature	Serial endocrinological testing
		CNS	Sleep apnea syndrome ID	Polygraphy/polysomnography

ASD, autism spectrum disorders; ASVD, atrioventricular septal defect; CNS, central nervous system; CT, computed tomography; ECG, electrocardiogram; GFR, glomerular filtration rate; EEG, electroencephalography; HbA1c, hemoglobin A1c; ID, intellectual disability; MECP2, methyl-CpG binding protein 2; MRI, magnetic resonance imaging; mTOR, mechanistic target of rapamycin; RLS, restless legs syndrome; tcCO2,transcutaneously measured carbon dioxide; TSC, tuberous sclerosis complex; TSH thyroid-stimulating hormone; TS- center, tuberous sclerosis center