In addition to intellectual and developmental disabilities, children with Down syndrome are at an increased risk for certain health problems. However, each individual with Down syndrome is different, and not every person will have serious health problems. Many of these associated conditions can be treated with medication, surgery, or other interventions.

Heart defects.

Almost one-half of babies with Down syndrome have congenital heart disease (CHD), the most common type of birth defect. The incidence of CHD in babies born with Down syndrome is up to 50%. The most common cardiac defect associated with Down syndrome is an atrioventricular septal defect (AVSD), and this defect makes up to 40% of the congenital cardiac defects in Down syndrome. The other cardiac defects associated with trisomy 21 are secundum atrial defect (10%), tetralogy of Fallot (6%), and isolated PDA (4%), while about 30% of the patients have more than one cardiac defect. Congenital cardiac defects are by far the most common cause associated with morbidity and mortality in patients with Down syndrome especially in the first 2 years of life. Because of such a high prevalence of CHD in patients with Down syndrome, it has been recommended that all patients get an echocardiogram within the first few weeks of life.

Gastrointestinal (GI) Tract Abnormalities

Patients with trisomy 21 have many structural and functional disorders related to the GI tract. Structural defects can occur anywhere from the mouth to anus, and it has been found that certain defects like duodenal and small bowel atresia or stenosis, annular pancreas, imperforate anus, and Hirschsprung disease occur more commonly in these patients as compared to the general population. About 2% of patients with Down syndrome have Hirschsprung disease while 12% of patients with Hirschsprung disease have Down syndrome. Hirschsprung disease is a form of functional lower intestinal obstruction in which the neural cells fail to migrate to the distal segment of the rectum resulting in an a ganglionic segment which does not have normal peristalsis resulting in failure of normal defecation reflex causing a functional obstruction. The infant usually presents with signs and symptoms related to intestinal obstruction. Duodenal atresia and imperforate anus usually present in the neonatal period. Apart from the structural defects, patients with Down syndrome, patients are also prone to many other GI disorders like gastroesophageal reflux (GERD), chronic constipation, intermittent diarrhoea, and celiac disease. Since there is a strong association of celiac disease with Down syndrome being present in about 5% of these patients, it is recommended to do yearly screening of celiac disease. Once diagnosed, these patients will have to remain on a gluten-free diet for the rest of life.

Hematologic Disorders

There are several haematological disorders associated with Down syndrome. The haematological abnormalities in a newborn with Down syndrome (HANDS) constitute neutrophilia, thrombocytopenia, and polycythaemia. Patients with Down syndrome are 10-times more at risk of developing leukaemia’s, which constitute about 2% of all paediatric acute lymphoblastic leukaemia and 10% of all paediatric acute myeloid leukaemia.

Neurologic Disorders

Trisomy 21 has associated with reduced brain volume especially hippocampus and cerebellum. Hypotonia is the hallmark of babies with Down syndrome and is present in almost all of them. It is defined as decreased resistance to passive muscle stretch and is responsible for delayed motor development in these patients. Because of hypotonia Down syndrome patients have joint laxity that causes decreased gait stability and increased energy requirement for physical exertion. These patients are prone to decreased bone mass and increased risk of fractures due to the low level of physical activity, while the ligamentous laxity predisposes these patients to atlantoaxial subluxation. Five percent to 13% of children with Down syndrome have seizures, out of that, 40% will have seizures before their first birthday, and in these cases, the seizures are usually infantile spasms. Down syndrome children with infantile spasm do respond better to antiepileptics as compared to other kids with the same, and therefore, early intervention and treatment improve the developmental outcome. Lennox-Gestaut syndrome is also seen to be more prevalent in children with Down syndrome when it does occur, has a late onset, and is associated with reflex seizures along with an increased rate of EEG abnormalities. Forty percent of patients with Down syndrome develop tonic-clonic or myoclonic seizures in their first 3 decades. Dementia occurs more commonly in patients older than 45 years of age with Down syndrome and about 84% are more prone to develop seizures. The seizures in these patients are related to the rapid decline in their cognitive functions. The risk of developing early-onset Alzheimer disease is significantly high in patients with Down syndrome with 50% to 70% of patients developing dementia by the age of 60 years. Nearly all the patients with Down syndrome have mild to moderate learning disability.

Endocrinological Disorders

Thyroid gland dysfunction is most commonly associated with Down syndrome. Hypothyroidism can be congenital or acquired at any time during life. Hyperthyroidism is much less frequent in patients with Down syndrome as compared to hypothyroidism. Abnormalities in sexual development are also noted to be significant with delayed puberty in both genders. In girls, primary hypogonadism presents as delay in menarche or adrenarche, while in boys it can manifest as cryptorchidism, ambiguous genitalia, micropenis, small testes, low sperm count, and scanty growth of axillary and pubic hair. The insulin-like growth factor is also said to be responsible for the and short stature in patients with Down syndrome.

Musculoskeletal Disorders

Children with Down syndrome are at an increased risk of reduced muscle mass because of hypotonia increased ligamentous laxity which causes retardation of gross motor skills and can result in joint dislocation. These patients also have vitamin D deficiency due to several factors like inadequate exposure to sunlight, inadequate intake of vitamin D, malabsorption secondary to celiac disease, increased breakdown because of anticonvulsant therapy, among other factors. These factors increase the risk of decreased bone mass in children with Down syndrome and predispose them to recurrent fractures.

Refractive Errors and Visual Abnormalities

Ocular and orbital anomalies are common in children with Down syndrome. These include blepharitis (2-7%), keratoconus (5-8%), cataract (25% to 85%), retinal anomalies (0% to 38%), strabismus (23% to 44%), amblyopia (10% to 26%), nystagmus (5% to 30%), refractive errors (18% to 58%), glaucoma (less than 1%), iris anomalies (38% to 90%) and optic nerve anomalies (very few cases). The ocular anomalies, if left untreated, can significantly affect the lives of these patients. Therefore, all the patients with Down syndrome should have an eye exam is done during the first 6 months of life and then annually.

Otorhinolaryngological ( ENT) Disorders

Ear, nose, and throat problems are also quite common in patients with Down syndrome. The anatomical structure of the ear in Down syndrome patients predisposes them to hearing deficits. Hearing loss is usually conductive because of impaction of cerumen and middle ear pathologies that include chronic middle ear effusion due to the small eustachian tube, acute otitis media, and eardrum perforation. These patients usually require pressure equalization tubes for the treatment. The sensorineural hearing loss has also been associated with Down syndrome because of the structural abnormalities in the inner ears such as narrow internal auditory canals. Early Intervention in Down’s syndrome can achieve a productive life at par with others.

When to evaluate and how frequently

What to check?	How to check?	When to be done?
Growth	Weight, height and head Circumference	Every 3 months during first year and then every year
Ear evaluation	BERA/OAE for hearing assessment / tympanometry	At least twice in first year, then every year
Eye evaluation	Cataract/refractory error	Every 6 months in first year Every year till the age of 5 year Every 2 years till the age of 12 years Every 3 years>12 years
Thyroid profile	T4 and T5H (thyroid hormones)	At initial contact at least at 6 month and at 12 months in first year and thereafter every year
Heart	EEG and ECHO	At initial contact. Then as per need
Sleep	Polysomnography (sleep studies)	Sleep studies for all by 4 years
Blood	Complete blood count	After 6 months in first year and then Annually till 12 years of age