Genetics/General

Question 1

CHARGE syndrome - stands for?

Major/Minor criteria?

Answer 1

Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genital hypoplasia, and Ear anomalies

There are Major and Minor criteria which define definite vs. probable CHARGE syndrome. Colobomas, choanal atresia, CN dysfunction/anomalies, and external ear anomalies are all MAJOR criteria. Minor criteria includes the rest + cleft palate, TE fistulas

Question 2

CHARGE - mutation?

Answer 2

CHD7 gene mutation analysis to confirm the disorder (present in 65-70% of cases).

CHD7 = chromodomain helicase DNA-binding protein 7 gene

Question 3

Syndrome: congenital heart disease, palatal abnormalities, facial features (low set ear, ocular hypertelorism, bulbous nose), learning problems, hypocalcemia, immune deficiency, kidney abnormalities, and hearing loss

Answer 3

22q11.2 - DiGeorge.

Question 4

Syndrome/gene: deafness, external ear deformities, lateral semicircular canal hypoplasia, branchial arch anomalies, and renal malformations

Answer 4

Branchio-oto-renal syndrome: BOR is caused by mutations of EYA1 and SIX1

Question 5

Syndrome/gene: mandibular and zygomatic hypoplasia, coloboma of the lower eyelids, absent lower eyelashes, external ear abnormalities, and preauricular hair displacement onto the cheekbones

Answer 5

Treacher Collins syndrome : Diagnosis is made via clinical and radiographic findings. Genetic testing is available for the 3 genes known to cause this disorder: TCOF1, POLR1C, and POLRID.

Question 6

What organs need to be evaluated in a child with suspected CHARGE syndrome

Answer 6

Urgent evaluation of the heart, airway, gastrointestinal tract, and genitourinary tract, improves morbidity and mortality and optimizes outcome. Hearing should also be evaluated.

Question 7

Colobomas are associated with?

Answer 7

Renal coloboma syndrome, CHARGE, Walker-Warburg, Goldenhar, Aicardi and Noonan

Question 8

Neonate with hypotonia, decreased activity, encephalopathy, seizures, craniofacial dysmorphisms, shortened proximal limbs - consider __ do and test for __.

Answer 8

peroxismal, VLCFA (very long chain fatty acids - elevated in nearly all peroxismal do)

Question 9

Psychomotor retardation, neurologic dysfunction, hearing loss, abnormal brain auditory evoked potential, visual abnormalities in children between 6 mo to 4 years can be signs of __ do.

Answer 9

Peroxismal disorders.

Question 10

In __ syndrome, patients have hepatomegaly associated with cirrhosis and biliary dysgenesis.

Answer 10

Zellweger

Question 11

Aniridia is most commonly associated with __.

Answer 11

WAGR - Wilm’s tumor, aniridia, genital abnormalitis, retardation

Question 12

Glaucoma can be associated with __ (congenital), but also causes including ROP, aniridia, exposure to steroids

Answer 12

Sturge Weber

Question 13

Multiple bacterial infections, neutropenia, anemia, thrombocytopenia + skeletal abnormalities/short stature + daily diarrhea and pancreatic insufficiency

Answer 13

Shwachman-Diamond syndrome

EPI (exocrine pancreatic insufficiency) is associated with cystic fibrosis, SD, chronic pancreatitis, Johanson-Blizzard (AR do with hypothyroid, DD, congenital anomalies) and Pearson syndromes (pancreatic fibrosis, severe anemia, other multi organ abnormalities).

Question 14

Marfan: what yearly screening do these patients need? (2)

Answer 14

Ocular - yearly slit-lamp, look for ectopic lentil, retinal detachment, glaucoma

Cardiology - aortic root dilatation, so yearly echos with intermittent whole-aorta surveillance.

Question 15

Pectus, scoliosis, and aortic root aneurysm - but also hypertelorism, bifid uvula, craniosynostosis, clef palate, generated arterial tortuosity with dissections along the arterial tree

Answer 15

Loeys Dietz syndrome, autosomal dominant presentation

Question 16

AD overgrowth syndrome with broad forehead, sparse frontotemporal hair, downslating palpebral fissures, long face, malar flushing. Usually head/height are >2SD above the mean, often have learning disabilities.

Answer 16

Sotos syndrome

Question 17

If parent has an elevated cholesterol >240 - guideline recommendations for children?

Answer 17

Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents states two fasting lipid profiles should be obtained.

Question 18

Noonan syndrome - common congenital heart defects?

Answer 18

Noonan syndrome presents with characteristic facial features, short stature, varying degrees of developmental delay, and congenital heart defects. Facial features include low-set ears with fleshy helices, broad or webbed neck, and wide-spaced, downslanting eyes with epicanthal folds. Common congenital heart defects include pulmonary valve stenosis, atrial septal defect, and hypertrophic cardiomyopathy. Wide-spaced nipples and an unusual chest shape with superior pectus carinatum/inferior pectus excavatum are typical. Microcephaly is not a common feature.

Question 19

Normal early growth and development (6-18 months) followed by a characteristic slowing of development, loss of purposeful hand movements, distinctive hand wringing, decreased brain growth (acquired microcephaly), loss of coordination, gait abnormalities, developmental regression, autistic-like behaviors, seizures, and intellectual disability. Apraxia and breathing difficulties while awake are quite common. Diagnosis commonly is made at 2 to 3 years of age.

Answer 19

Rett syndrome, caused by the MECP 2 gene mutation, is an X-linked neurodevelopmental disorder that predominantly affects girls

Question 20

Pre-auricular pit evaluation?

Specifically, what are we looking for?

Answer 20

For newborns with an isolated, unilateral preauricular pit or skin tag and no other risk factors, the risk of renal anomalies is, at most, slightly higher than in the general population.

In newborns with external ear anomalies who have other congenital anomalies or dysmorphic features, a family history of deafness, ear, or renal anomalies, or a maternal history of gestational diabetes, the likelihood of clinically significant structural renal anomalies is higher, and renal ultrasonography is warranted. Outer and middle ear anomalies include microtia, protruding ears, external auditory canal atresia, and malformations of the ossicles in the middle ear.

In newborns with external ear abnormalities, 5% to 40% will have congenital anomalies involving other organs. Ear and/or renal anomalies are associated with several genetic syndromes. Such conditions include CHARGE syndrome (coloboma, heart defects, atresia choanae, poor growth and/or intellectual disability, urogenital anomalies, and ear anomalies), DiGeorge syndrome (22q11.2 deletion), and branchio-oto-renal syndrome.

Question 21

BPH first line tx
BPH second line tx

BPH + erectile dysfunction treatment

Answer 21

1st line: tamsulosin
2nd line: finasteride - but can worsen ED

Tadalafil if you need to treat both

Question 22

What test is necessary for diagnosis of narcolepsy or idiopathic hypersomnia?

Answer 22

multiple sleep latency testing (MSLT)