A Patient Wants to Know the Risk Factors for Down Syndrome. What Is the Nurseã¢â‚¬â„¢s Best Response

Continuing Education Activeness

Down syndrome (trisomy 21) is a genetic disorder caused by the presence of all or a portion of a third chromosome 21. Patients typically present with mild to moderate intellectual disability, growth retardation, and characteristic facial features. This activity reviews the evaluation and direction of Down syndrome and explains the role of the interprofessional team in improving treat patients with this status.

Objectives:

• Describe the etiology of Down syndrome.

• Identify atrial septal defects every bit the most common cardiac abnormalities in patients with Downwards syndrome.

• Summarize the use of ultrasound, amniocentesis and chorionic villus sampling in the pre-natal diagnosis of Down syndrome.

• Outline the importance of collaboration and advice among the interprofessional squad to enhance the delivery of care and improve outcomes for patients affected by Down syndrome.

Access free multiple choice questions on this topic.

Introduction

Down syndrome was showtime described by an English physician John Langdon Downwards in 1866, simply its association with chromosome 21 was established almost 100 years later on by Dr. Jerome Lejeune in Paris. It is the presence of all or part of the third copy of chromosome 21 which causes Downwards syndrome, the virtually mutual chromosomal abnormality occurring in humans.[i] Information technology is also institute that the well-nigh frequently occurring live born aneuploidy is trisomy 21 that causes this syndrome.[2]

Etiology

The bulk of patients with Downward syndrome have an actress re-create of chromosome 21. There are different hypothesis related to genetic ground of Down syndrome and association of unlike genotypes with the phenotypes. Among them is gene dosage imbalance in which there is an increased dosage or number of genes of Hsa21, which results in increased gene expansion.[3]. It further includes the possibility of clan of different genes with different phenotypes of Down's syndrome. The other popular hypothesis is amplified evolution instability hypothesis, according to which the genetic imbalance created by a number of trisomic genes and results in a greater impact on the expression and regulation of many genes.[3]

Critical region hypothesis is as well well known in this list. Down syndrome critical regions (DSCR) are few chromosomal regions which are associated with partial trisomy for Has21. DSCR on 21q21.22 is responsible for many clinical features of Down's syndrome.[3][iv] Afterward a thorough written report of different analyses, it became clear that a unmarried disquisitional region gene cannot cause all the phenotypical features associated with trisomy 21, rather it is more evident that multiple critical regions or disquisitional genes accept a role to play in this phenomenon.[v]

Epidemiology

The incidence of Down syndrome increases with maternal historic period, and information technology occurrence varies in different population (1 in 319 to 1 in grand live births)[6][vii], it is also known that the frequency of Down syndrome fetuses is quite high at the time of formulation, but well-nigh 50% to 75% of these fetuses are lost before term. The occurrence of other autosomal trisomy is much more common than the 21, but the postnatal survival is very poor equally compared to Down's syndrome. This high percent of survival of patients with trisomy 21 is thought to be a part of a small number of genes on chromosome 21 called Hsa21, which is the smallest and least dense of the autosomes.[viii]

Pathophysiology

An extra copy of chromosome 21 is associated with Downward syndrome, which occurs due to the failure of chromosome 21 to split up during gametogenesis resulting in an extra chromosome in all the body cells. Robertsonian translocation and isochromosome or ring chromosome are the other ii possible causes of trisomy 21. Isochromosome is a condition when 2 long arms separate together instead of the long and short arm while in Robertsonian translocation. This occurs in 2% to four% of the patients. The long arm of chromosome 21 is attached to another chromosome, mostly chromosome fourteen. In mosaicism, there are ii dissimilar cell lines because of error of partition later on fertilization.[half dozen]

History and Physical

Clinical Features

Different clinical atmospheric condition are associated with Down's syndrome every bit different systems are affected by it. These patients have a broad array of signs and symptoms like intellectual and developmental disabilities or neurological features, built heart defects, gastrointestinal (GI) abnormalities, feature facial features, and abnormalities.[9]

Congenital Cardiac Defects (CHD)

Congenital cardiac defects are by far the most common and leading cause associated with morbidity and mortality in the patients with Down syndrome particularly in the first 2 years of life. Though different suggestions have been made about the geographical as well as seasonal variation in the occurrence of different types of congenital cardiac defects in trisomy 21, and then far none of the results take been conclusive.[ten]

The incidence of CHD in babies built-in with Down syndrome is upwards to 50%. The about 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's syndrome.[6] Information technology is said to be associated with the mutation of the non-Hsa21 CRELD1 gene[6][11] The second virtually mutual cardiac defect in Down syndrome is a ventricular septal defect (VSD), which is seen in about 32% of the patients with Down's syndrome. Together with AVSD, these account for more than fifty% of congenital cardiac defects in patients with Down syndrome.[6][xi]

The other cardiac defects associated with trisomy 21 are secundum atrial defect (ten%), tetralogy of Fallot (6%), and isolated PDA (4%), while nearly 30% of the patients have more than than one cardiac defect. There is geographical variation in the prevalence of the cardiac defect in Down's syndrome, with VSD being the most common in Asia and secundum type ASD in Latin America. The reason backside this difference in the prevalence of different types of CHD in dissimilar regions is still unclear, and many factors such every bit regional proximity take been found to contribute.[6]

Considering of such a high prevalence of CHD in patients with Down syndrome, information technology has been recommended that all patients get an echocardiogram within the kickoff 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 tin can occur anywhere from the rima oris to anus, and it has been found that certain defects like duodenal and minor bowel atresia or stenosis, annular pancreas, imperforate anus, and Hirschsprung illness occur more unremarkably in these patients as compared to the general population.[1]

Well-nigh 2% of patients with Down syndrome have Hirschsprung disease while 12% of patients with Hirschsprung disease have Downwards syndrome.[1][6] Hirschsprung disease is a form of functional lower intestinal obstacle in which the neural cells fail to migrate to the distal segment of the rectum resulting in an aganglionic segment which does non have normal peristalsis resulting in failure of normal defecation reflex causing a functional obstruction.[12] The baby usually presents with signs and symptoms related to intestinal obstruction. Duodenal atresia and imperforate anus unremarkably nowadays in the neonatal period.

Apart from the structural defects patients with Down's syndrome, patients are also decumbent to many other GI disorders like gastroesophageal reflux (GERD), chronic constipation, intermittent diarrhea, and celiac disease. Since at that place is a strong clan of celiac affliction with Down syndrome being present in nigh five% of these patients, it is recommended to practise yearly screening of celiac disease. Once diagnosed, these patients will have to remain on a gluten-free diet for the rest of life.[13]

Hematologic Disorders

In that location are several hematological disorders associated with Down's syndrome. The hematological abnormalities in a newborn with Down syndrome (Easily) constitute neutrophilia, thrombocytopenia, and polycythemia, which are seen in lxxx%, 66% and 34% of Downwards syndrome babies respectively.[14][fifteen][16] Easily is unremarkably balmy and resolves within the first thr3e weeks of life.[fourteen][15][16]

The other disorder that is quite specific to Down's syndrome is a transient myeloproliferative disorder, which is defined as detection of blast cells in younger than 3 month old babies with Down syndrome. It is characterized by the clonal proliferation of megakaryocytes and is detected during the first week of life and is resolved by 3 months of life. It is also known as transient aberrant myelopoiesis or transient leukemia and is known to be present in almost ten% of patients with Down syndrome. If this occurs in the fetus, it tin cause spontaneous ballgame.[17][18]

Patients with Down syndrome are x-times more at run a risk of developing leukemia,[19] which constitute about 2% of all pediatric acute lymphoblastic leukemia and 10% of all pediatric acute myeloid leukemia. Thirty percent of Down's syndrome patients with acute lymphoblastic leukemia take an clan with part mutation in Janus Kinase ii gene.[20]

About 10% of patients with chronic myeloid leukemia (TML) develop leukemogenesis of acute megakaryoblastic leukemia (AMKL) before the age of 4 years. AMKL is associated with GATA1 gene which is an X-linked transcriptor factor leading to an uncontrolled proliferation of immature megakaryocytes.[21]

Neurologic Disorders

Trisomy of Hsa21 has associated with reduced brain volume peculiarly hippocampus and cerebellum.[22] Hypotonia is the authentication of babies with Down syndrome and is nowadays in almost all of them. It is defined equally decreased resistance to passive musculus stretch and is responsible for delayed motor development in these patients.[23]. Because of hypotonia Down's syndrome patients have joint laxity that causes decreased gait stability and increased energy requirement for physical exertion.[24]. These patients are prone to decreased bone mass and increased take chances of fractures due to the low level of physical activity[25], while the ligamentous laxity predisposes these patients to atlantoaxial subluxation.[26]

Five percent to 13% of children with Down syndrome accept seizures[27], out of that, twoscore% will have seizures before their first birthday, and in these cases, the seizures are usually infantile spasms.[28] Down's syndrome children with infantile spasm do reply better to antiepileptics as compared to other kids with the same, and therefore, early on intervention and treatment improve the developmental result.[27]

Lennox-Gestaut syndrome is also seen to be more prevalent in children with Downwardly syndrome when it does occur, has a late onset, and is associated with reflex seizures along with an increased rate of EEG abnormalities.[29]

Twoscore pct of patients with Down syndrome develop tonic-clonic or myoclonic seizures in their first 3 decades.[28] Dementia occurs more commonly in patients older than 45 years of historic period with Downward syndrome[30], and about 84% are more decumbent to develop seizures.[31] The seizures in these patients are related to the rapid decline in their cognitive functions.[32]

The risk of developing early-onset Alzheimer disease is significantly high in patients with Downwardly syndrome with 50% to seventy% of patients developing dementia by the age of sixty years.[33] Amyloid forerunner poly peptide (APP), which is known to exist associated with increased chance for the Alzheimer disease is found to be encoded on Hsa21, and trisomy of this protein is probable to be responsible for increased frequency of dementia in people with Down's syndrome. Contempo studies take shown that triplication of APP is associated with increased hazard of early-onset Alzheimer disease even in the normal population.[34]

Near all the patients with Down's syndrome have mild to moderate learning disability. Trisomy of multiple genes including DYRK1A, synaptojanin 1, and single-minded homolog ii (SIM2) have been found to crusade learning and retentivity defects in mice, which suggests the possibility that the overexpression of these genes may likely be causing the learning disability in people with Down's syndrome.[35]

Endocrinological Disorders

Thyroid gland dysfunction is most commonly associated with Down syndrome. Hypothyroidism can exist congenital or acquired at any time during life.[25] The newborn screening program in New York has reported an increased incidence of congenital hypothyroidism in babies with Downwardly syndrome every bit compared to the others.[36] The anti-thyroid autoantibodies were constitute in 13% to 34% of patients with Downward syndrome who had acquired hypothyroidism, and the concentration of these antibodies increased after 8 years of life.[25]. About half of the patients with Down syndrome have been shown to take subclinical hypothyroidism with elevated TSH and normal thyroxine levels.[37] Hyperthyroidism is much less frequent in patients with Down syndrome as compared to hypothyroidism, although the charge per unit of it still exceeds the incidence of hyperthyroidism in the full general pediatric population.[38]

Abnormalities in sexual development are besides noted to be pregnant 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, depression sperm count, and scanty growth of axillary and pubic hair.[25]

 The insulin-like growth factor is too said to be responsible for the delay in skeletal maturation and short stature in patients with Downwardly syndrome.[25]

Musculoskeletal Disorders

Children with Down's syndrome are at an increased chance of reduced muscle mass because of hypotonia increased ligamentous laxity which causes retardation of gross motor skills and can issue in articulation dislocation.[39] 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 illness, increased breakdown considering 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.[40]

Refractive Errors and Visual Abnormalities

Ocular and orbital anomalies are common in children with Down's syndrome. These include blepharitis (2-7%), keratoconus (five-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 xc%) and optic nervus anomalies (very few cases).

The ocular anomalies, if left untreated, can significantly impact the lives of these patients. Therefore, all the patients with Down's syndrome should have an eye examination is done during the commencement 6 months of life then annually.[41]

Otorhinolaryngological ( ENT) Disorders

Ear, nose, and throat issues are also quite common in patients with Down syndrome. The anatomical structure of the ear in Down's 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 modest 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.[42]

Evaluation

There are different methods used for the prenatal diagnosis of Down syndrome. Ultrasound between xiv and 24 weeks of gestation can exist used every bit a tool for diagnosis based on the soft markers like increased nuchal fold thickness, small-scale or no nasal bone and large ventricles.[43] Amniocentesis and chorionic villus sampling had widely been used for the diagnosis, simply there is a pocket-sized risk of miscarriages between 0.five% to 1%.[44]

Several other methods accept also been developed and are used for the rapid detection of trisomy 21 both during the fetal life and after birth. The most commonly used is FISH of interphase nuclei by either using Hsa21 specific probes or whole of the Hsa21.[45] Another method which is currently beingness used is QF-PCR, which the presence of iii dissimilar alleles is adamant past using DNA polymorphic markers.[46] The success of this method depends upon the informative markers and the presence of Deoxyribonucleic acid. Information technology has been institute that upwards to 86.67% of cases of Down syndrome can be identified past using the STR mark method.[47]

A relatively new method chosen as paralogue sequence quantification (PSQ) uses the paralogue sequence on Hsa21 copy number. It is a PCR based method that uses the paralogue genes to detect the targeted chromosome number abnormalities which are known equally paralogue sequence quantification.[48]

There are non-invasive prenatal diagnostic methods which are being studied to be used for the diagnosis of Downward syndrome prenatally. These are based on the presence of fetal cells in the maternal blood and the presence of cell-costless fetal DNA in the maternal serum. [49]

Cell-free fetal Deoxyribonucleic acid makes upward 5% to ten% of the maternal plasma, and it increases during pregnancy and clears after delivery. Though this method has been used to determine fetal Rh status in Rhive women[50], sex in the sex-linked disorders[51], and for the detection of paternally inherited autosomal recessive and dominant trait,[52] just its utilise for the detection of chromosomal aneuploidy especially the trisomy is even so a challenge.

Few other recent methods like digital PCR and next-generation sequencing (NGS) are as well being developed for the diagnosis of Down syndrome.[53]

Treatment / Direction

The management of patients with Down's syndrome is multidisciplinary. Newborn with suspicion of Down's syndrome, should accept a karyotyping done to confirm the diagnosis. The family needs to exist referred to the clinical geneticist for the genetic testing and counseling of both the parents.

Parental education is one of the foremost aspects regarding the management of Downward syndrome, equally parents need to be enlightened of the different possible atmospheric condition associated with information technology then that they tin can be diagnosed and treated appropriately. Treatment is basically symtomatic and consummate recovery is not possible.

These patients should take their hearing and vision assessed and every bit they are more prone to have a cataract, therefore timely surgery is required. Thyroid function tests should be done on a yearly basis and if deranged should exist managed appropriately.

A balanced diet, regular do, and concrete therapy are needed for the optimum growth and weight proceeds, although feeding problems do improve subsequently the cardiac surgery.

Cardiac referral should exist sent for all the patients regardless of the clinical signs of congenital heart disease which if nowadays should be corrected within the first 6 months of life to ensure optimum growth and development of the kid.

Other specialties involved include a developmental pediatrician, pediatric pulmonologist, gastroenterologist, neurologist, neurosurgeon, orthopedic specialist, child psychiatrist, physical and occupational therapist, speech and language therapist, and audiologist.

Differential Diagnosis

• Congenital hypothyroidism

• Mosaic trisomy 21 syndrome

• Fractional trisomy 21(or 21q duplication)

• Robertsonian trisomy 21

• Trisomy 18

• Zellweger syndrome or other peroxisomal disorders

Prognosis

With the recent advances in the medical practice, evolution of surgical techniques for the correction of congenital disabilities and improvement in general care there has been a tremendous increase in the survival of infants and life expectancy of patients with Down's syndrome. A Birmingham (United kingdom) study washed almost 60 years ago showed that 45% of the infants survived the outset year of life, and only xl% would be alive at v years.[54] A later study conducted about fifty years afterward that showed 78% of patients with Down syndrome plus a congenital centre defect survived for i year, while the number went up to 96% in patients without the anomalies.[55] This ascension in the life expectancy of these patients should continue to rise significantly because of the developments in medical scientific discipline. Healthcare facilities aim to provide proper and timely management to these patients and to help them to have a fulfilled and productive life.[56]

Enhancing Healthcare Squad Outcomes

The management of patients with Downwardly syndrome is an interprofessional effort. Newborns with suspicion of Down syndrome, should have a karyotyping done to ostend the diagnosis. The family unit needs to be referred to the clinical geneticist for the genetic testing and counseling of both the parents.

Because nearly every organ system is involved the child needs to exist seen by the ophthalmologist, orthopedic surgeon, cardiologist, dermatologist, gastroenterologist, concrete therapist, mental wellness nurse, ENT surgeon and a beliefs specialist.

Parental education is one of the foremost aspects regarding the direction of Down syndrome, as parents demand to be aware of the different possible conditions associated with information technology so that they tin be diagnosed and treated appropriately. Treatment is basically symtomatic and complete recovery is not possible.

While life span has increased over the past iii decades, these indivduals nonetheless have a shorter life expectancy compared to healthy individuals.

Review Questions

Figure

A cropped photo of the eyes of a baby with Downwardly Syndrome. Brushfield spots are visible between the inner and outer circle of the iris. Contributed by Wikimedia Eatables, Szymon Tomczak (Public Domain)

Figure

"This photo depicts a newborn with the genetic disorder Down's syndrome, due to the presence of an actress 21st chromosome.". Contributed past The Centers for Disease Control and Prevention -- ID# 2634/Dr. Godfrey P. Oakley (Public Domain)

Figure

Karyotype for trisomy Down syndrome: Notice the three copies of chromosome 21. Contributed by The National Human being Genome Research Establish, Human Genome Project

Effigy

A cartoon of the facial features of Downwards syndrome. Contributed by the Centers for Illness Control and Prevention, National Center on Birth Defects and Developmental Disabilities (Public Domain)

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Source: https://www.ncbi.nlm.nih.gov/books/NBK526016/

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