29 Flashcards
Diff dx of hypotonia in a newborn 4
Down syndrome Remember that almost all of the findings in can be seen individually in people who do not have Down syndrome. It is the combination of findings that separates a syndrome from normal variation.
Benign neonatal hypotonia Generally not associated with unusual facial or hand features.
Zellweger syndrome Infants with Zellweger syndrome—a peroxisomal disorder—are generally hypotonic and poorly responsive.
Family resemblance While family resemblance may account for one or two clinical findings in a child, it is usually not several findings associated with a syndrome.
Common features of Down syndrome and what is the most common feature seen
Common features of more than 50% of infants with Down syndrome include:
Upslanting palpebral fissures
Small ears (usually less than 34 mm at maximum dimension in a term infant)
Flattened midface
Epicanthal folds ( skin fold of the upper eyelid, covering the inner corner (medial canthus) of the eye)
Redundant skin on back of neck (nuchal skin)
Hypotonia (most consistent finding in infants with Down syndrome)
Short height is a common finding in children with Down syndrome
Chromosome involved in Down syndrome (3 karyotypes)
There are several karyotypes involving extra material from chromosome 21 that can cause the Down syndrome phenotype, including:
Trisomy 21 (47, XY,+21 in this boy) (the most common and most likely, regardless of the mother’s age);
An unbalanced chromosome translocation resulting in extra chromosome 21 material; and
Mosaicism for a trisomy 21 cell line means cells have more than one type of chromosomal makeup ( some cells have trisomy 21 and other cells have typical number)
The likelihood of finding a translocation increases in infants born to younger mothers, but trisomy is still most likely, regardless of the parental age.
Diagnostic testing for Down syndrome
Lymphocyte karyotype remains the standard for the laboratory diagnosis of Down syndrome.
Fluorescence in-situ hybridization (“FISH”) studies of uncultured cells have not replaced lymphocyte karyotype as the diagnostic study of choice.
Although cytogenetic studies can be done on skin fibroblasts, it is much easier to obtain and study peripheral blood lymphocytes.
While echocardiography may be indicated as part of the evaluation, at least 50% of infants with Down syndrome will have normal cardiac anatomy, and the finding of a cardiac malformation by echocardiogram does not necessarily confirm the diagnosis of Down syndrome.
What on a newborn screening test would most likely be abnormal in a child with Down syndrome
Infants with Down syndrome have an increased chance of having hypothyroidism.
Before the advent of cytogenetic testing, there was frequently diagnostic confusion between infants with Down syndrome and those with congenital hypothyroidism.
Now that diagnostic cytogenetic testing is available for Down syndrome, it is interesting to note that the incidence of hypothyroidism is increased in infants with Down syndrome (both congenital hypothyroidism and also hypothyroidism that develops later in childhood).
F/u evaluation for children with Down syndrome 7
The following referrals or evaluations are recommended during the first 10 years of life of a child with Down syndrome:
Annual thyroid screening (due to an increased incidence of hypothyroidism, even if not present at birth)
Vision screening (due to increased incidence of vision problems)
Hearing screening (due to increased incidence of hearing problems)
Complete blood count in first month to assess for leukemoid reactions, or transient myeloproliferative disorders (TMD - hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow )
Referral to a pediatric cardiologist (due to the increased incidence [50%] of structural heart disease in patients with Down syndrome and the difficulty of auscultating some of these cardiac defects) - Approximately 50% of children with Down syndrome are born with endocardial cushion defects, such as ventricular septal defect, atrial septal defect, or complete atrioventricular canal defect.
Beginning at 1 year of age, and then annually, a hemoglobin and hematocrit should be obtained to screen for iron deficiency anemia (due to increased risk for iron deficiency due to lower dietary iron intake than their peers)
Referral for evaluation by early intervention is key to a child with Down syndrome receiving any needed therapies as early as possible.
Additionally, there is an increased incidence of atlantoaxial instability in individuals with Down syndrome, so careful history and physical examinations should be performed at every well-child visit or when symptoms possibly attributable to spinal cord impingement are reported. At least biennially, the importance of cervical spine-positioning precautions for protection of the cervical spine during any anesthetic, surgical, or radiographic procedure should be discussed with parents.
Prenatal testing vs screening for Down syndrome 2 and 2
Testing
Chromosome analyses of amniotic fluid cells and chorionic villous sampling (CVS) are both direct diagnostic tests for Down syndrome, because the cells that are obtained and analyzed are of fetal origin.
Both amniocentesis and CVS do have risks of complications, particularly a slight risk of causing a miscarriage.
(In addition, there is a newer diagnostic method that is being used for the diagnosis of Down syndrome as early as the first trimester. This test, which measures fetal-specific DNA sequences in a maternal blood sample, can detect Down syndrome with 98.6% certainty.)
Screening
Maternal serum screening and fetal ultrasound can potentially screen for Down syndrome (and other chromosomal abnormalities); that is, they can provide information about the risk of having an affected fetus, but cannot definitively diagnose for a specific condition:
Measurement of analytes in maternal serum offers an indirect screening method that can help refine the risk that a fetus is affected; the specific analytes measured vary, and may include alphafetoprotein, human chorionic gonadotropin, estriol, PAPP-A, and/or inhibin. This is a rapidly developing area, and newer tests and combinations of tests may be available. These tests are not specific for Down syndrome, however.
Detailed ultrasonography, looking at nuchal skin thickness, nasal bone ossification and other growth parameters, has been used to identify fetuses at increased risk for having Down syndrome. Ultrasound may be used in combination with maternal age and analyte measurement to better refine the risk that a fetus is affected with Down syndrome or another common chromosomal abnormality.
most common familial cause of intellectual disability
Fragile X is an X-linked disease caused by the inheritance of an abnormal number of CGG repeats in the FMR1 gene.
Physical features of Fragile X syndrome include:
long face with a large mandible
large, prominent ears
large testicles (after puberty)
may include evidence of a mild connective tissue abnormality (joint laxity, pectus excavatum, flat feet)
Females: Females with a full mutation range from being asymptomatic to having mental retardation and/or psychiatric or behavioral problem
With the exception of Down syndrome, Fragile X syndrome is the most common genetic cause of intellectual disability.
45, XO genetic abnormality
Turner syndrome is the sex chromosomal disorder most likely to be associated with physical differences at birth.
Physical findings
Turner syndrome is associated with lymphedema in utero, which is the cause of many of the physical findings such as:
Webbed neck Low ear placement Edema of the hands and feet Hyperconvex nails, and "Shield" chest, with widely spaced nipples Additional findings in Turner syndrome:
Coarctation of the aorta is found in about 20% of affected girls.
Short stature is common, and some girls are not diagnosed until early adolescence when they present with short stature and delayed sexual maturation (due to gonadal dysgenesis).
Most have a normal IQ.
Incidence
The incidence of Turner syndrome is about 1/2,000 female live births, but the incidence at conception is much higher. It is estimated that about 99% of conceptuses with Turner syndrome miscarry, most in the first trimester.
47 XXY
Klinefelter Syndrome
Boys with Klinefelter syndrome are typically normal appearing at birth, and may not be diagnosed until adulthood.
Findings vary but usually include infertility due to testicular atrophy.
There may be a eunuchoid body habitus (unusually long limbs compared to the body), and female hair distribution, tall stature and gynecomastia in adolescence.
IQ varies, but is usually in the low-normal range.
There is no specific phenotype for either 47, XXX or 47, XYY.
Developmental delay and decreased IQ is more common in 47, XXX.
Adults with 47, XYY may be taller than average.
IQ tends to be in the low-normal range.
There may be an increased incidence of behavior problems.
Trisomies 3 types
Trisomy 13 (patau syndrome)1 in 10,000 births Microphthalmia Microcephaly Severe intellectual disability Polydactyly Cleft lip and palate Cardiac and renal defects Umbilical hernias Cutis aplasia
Trisomy 18 (Edwards syndrome) 1 in 6,000 births Severe intellectual disability Prominent occiput Micrognathia Low-set ears Short neck Overlapping fingers Heart defects Renal malformations Limited hip abduction Rocker-bottom feet
Trisomy 21 (Down syndrome) 1 in 700 births Intellectual disability Epicanthic folds Flat facial profile Single palmar crease Redundant neck skin Heart defects Intestinal stenosis Umbilical hernia Predisposition to leukemia Hypotonia Gap between first and second toes
