29: 9-week-old male Infant with hypotonia

Question 1

Common features of more than 50% of infants with Down syndrome include:

Answer 1

• Upslanting palpebral fissures
• Small ears (usually less than 34 mm at maximum dimension in a term infant)
• Flattened midface
• Epicanthal folds
• Redundant skin on back of neck (nuchal skin)
• Hypotonia (most consistent finding in infants with Down syndrome)

Question 2

There are several karyotypes involving extra material from chromosome 21 that can cause the Down syndrome phenotype, including:

Answer 2

• 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.

Question 3

Down Syndrome and Hypothyroidism

Answer 3

Infants with Down syndrome have an increased chance of having hypothyroidism.

Question 4

Down Syndrome (Trisomy 21)

Answer 4

present in about 1 in 700 births in the U.S.

Question 5

DS screening

Answer 5

• -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.
• -Detailed US, 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. US 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.

Question 6

Physical features of Fragile X syndrome include

Answer 6

long face with a large mandible large, prominent ears
large testicles (after puberty)

Question 7

Fragile X

Answer 7

• X-linked disease caused by the inheritance of an abnormal number of CGG repeats in the FMR1 gene.
• With the exception of Down syndrome, Fragile X syndrome is the most common genetic cause of intellectual disability.

Question 8

Turner syndrome is associated with lymphedema in utero, which is the cause of many of the physical findings such as:

Answer 8

Webbed neck
Low ear placement
Edema of the hands and feet 
Hyperconvex nails
"Shield" chest, with widely spaced nipples

Question 9

Additional findings in Turner syndrome:

Answer 9

• -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.

Question 10

Klinefelter Syndrome

Answer 10

• Findings vary but usually include infertility due to testicular atrophy.
• There may be a eunuchoid body habitus and gynecomastia in adolescence.
• IQ varies, but is usually in the low-normal range.

Question 11

Trisomy 13 (Patau syndrome)

Answer 11

Microphthalmia 
Microcephaly
Severe intellectual disability 
Polydactyly
Cleft lip and palate
Cardiac and renal defects 
Umbilical hernias
Cutis aplasia

Question 12

Trisomy 18 (Edwards syndrome)

Answer 12

Severe intellectual disability 
Prominent occiput
Micrognathia 
Low-set ears
Short neck 
Overlapping fingers 
Heart defects
Renal malformations 
Limited hip abduction 
Rocker-bottom feet

Question 13

Trisomy 21 (Down syndrome)

Answer 13

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

Question 14

The following referrals or evaluations are recommended during the first 10 years of life of a child with Down syndrome:

Answer 14

• -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)
• -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)
• -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.

Question 15

Diagnostic Testing for Trisomy 21

Answer 15

Lymphocyte karyotype remains the standard for the laboratory diagnosis of Down syndrome.

Question 16

Differential Diagnosis of Hypotonia in a Newborn

Answer 16

1. DS
2. Benign neonatal hypotonia
3. Zellweger syndrome
4. family resemblance

Question 17

A 4-year-old male with a history of Down syndrome and no other medical problems is brought to his pediatrician’s office by his mother for increasing fatigue, intermittent fever, and decreased appetite for one week. On exam you note conjunctival pallor and hepatosplenomegaly. What is the best next step in the management of this patient?

Answer 17

This choice is correct because fatigue, decreased appetite, anemia, and HSM are all clinical signs and symptoms that may be associated with acute leukemia, for which patients with Down syndrome are at increased risk. A CBC would be helpful both for assessing the white blood cell count as well as the degree of anemia. A peripheral smear would be indicated to further evaluate for leukemia.

Question 18

Endocardial cushion defects

Answer 18

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.

Question 19

Turner syndrome

Answer 19

karyotype 45 XO. Characteristics of females with Turner syndrome include renal abnormalities, lymphedema (causing edema of hands and feet), low-set ears, congenital heart defects, dental abnormalities-such as narrow or high-arched palates-and cystic hygromas. Other possible physical findings include a webbed neck, widely-spaced nipples, and shield-like chest. As this mother did not have prenatal testing or a karyotype performed previous to her daughter’s birth, one should be performed to confirm the diagnosis

Question 20

Edwards syndrome

Answer 20

caused by an extra chromosome 18. These infants present with severe mental retardation, micrognathia (small jaw), low-set ears, short neck, overlapping fingers (digits 2 and 5 overlap medially upon closure of fist), heart defects, renal malformations, limited hip abduction, and “rocker-bottom” feet (the plantar side of foot has a u-shaped curve like a rocking chair).

Question 21

Patau syndrome

Answer 21

due to an extra chromosome 13. Presentation includes a general theme of shifting facial features toward the midline: microphthalmia (some present with a midline Cyclops eye), microcephaly with severe mental retardation, polydactyly, cleft lip and palate, cardiac and renal defects, umbilical hernias, and cutis aplasia (particularly in the midline of the scalp).