Genetics

Question 1

What are the characteristic clinical features common to all types of osteogenesis imperfecta (OI)?

Answer 1

Osseous fragility, short stature, other skeletal findings
Explanation
All types of OI are caused by an abnormal structure of Type 1 collagen. None of these forms cause retinal hemorrhage or subdural hematomas, which distinguishes OI from abuse.

Question 2

What are the most common heart defects seen in trisomy 21 (a.k.a. Down syndrome)?

Answer 2

Of those with heart defects:
1/3 have atrioventricular (AV) canal defects.
1/3 have ventricular septal defects.
1/3 have atrial septal defects of the secundum variety and tetralogy of Fallot.
Explanation
~ 50% of children with trisomy 21 have a cardiac defect; therefore, echocardiogram is mandatory. Remember: AV canal defects commonly do not have an associated murmur!

Question 3

What are the complications associated with achondroplasia?

Answer 3

Serous otitis media, motor milestone delay, bowing of legs, orthodontic problems
Serious complications of spinal cord compression: apnea, quadriparesis, growth delay, hydrocephalus
Explanation
Foramen magnum stenosis and/or craniocervical junction abnormalities can occur in infancy and cause compression of the upper cord, resulting in the serious complications listed above. Most males have final heights of 46–57 inches and females of 44–54 inches. Adults are at risk for obesity and spinal stenosis

Question 4

A 6-year-old boy presents to you as a new patient with the following:

Periorbital fullness
Wide mouth, full lips
Very friendly personality
Stellate pattern of the iris
Strabismus
Intellectual disability
What is the most likely diagnosis?

Answer 4

Williams syndrome (7q11.23 deletion)
Explanation
Williams syndrome is due to a microdeletion on the long arm of chromosome 7. Classically, we think of this as an individual having a “cocktail party” personality with the clinical findings listed. These children are missing the elastin gene from 1 of their 2 copies of chromosome 7.

Question 5

You are given a pedigree with the following characteristics:

Both sexes are equally affected.
Both sexes can transmit to offspring.
Disorders may be seen in 1 or more siblings but not in all generations.
Consanguinity increases the risk of having an affected offspring.
What is the most likely classic Mendelian inheritance pattern?

Answer 5

Answer
Autosomal recessive (AR)
Explanation
AR disorders require 2 copies of an altered allele to produce a disease phenotype. AR disorders are less common than autosomal dominant disorders; however, heterozygote carriers are much more common in the general population. Cystic fibrosis is a classic example.

Question 6

An infant presents with the following:

Pancytopenia
Hypoplastic thumb and radius
Hyperpigmentation
Abnormal facial features
What is the most likely diagnosis?

Answer 6

Answer
Fanconi anemia
Explanation
Fanconi anemia is a rare autosomal recessive disorder that presents with the listed features. It is a chromosome instability syndrome resulting from the mutation of multiple genes.

Question 7

A young child presents with:

Generalized overgrowth
Macroglossia
Ear lobe creases
Posterior auricular pits
History of omphalocele
Cryptorchidism
Hemihypertrophy
Large for gestational age
What is the most likely diagnosis?

Answer 7

Answer
Beckwith-Wiedemann syndrome
Explanation
Beckwith-Wiedemann syndrome is an autosomal dominant disorder with the features listed. Remember: Wilms tumor is likely in these children.

Question 8

What cancer is most likely to occur in a child with trisomy 21 (a.k.a. Down syndrome)?

Answer 8

Answer
Leukemia
Explanation
Leukemia—particularly acute lymphoblastic leukemia—has a markedly increased incidence in children with trisomy 21, and the child should be monitored throughout childhood and into adulthood.

Question 9

An 18-year-old presents with the following:

Hearing loss
Tinnitus
Imbalance
Facial weakness
Opaque lens with the right eye having a cataract
What is the most likely diagnosis?

Answer 9

Neurofibromatosis Type 2 (NF2)
Explanation
NF2 is an autosomal dominant disorder characterized by bilateral vestibular schwannomas that result in hearing loss, tinnitus, imbalance, and facial weakness. The mean age of onset of these schwannomas is 18–24 years. By 30 years of age, all affected individuals have developed bilateral vestibular schwannomas. Children are frequently diagnosed with the disorder as cataracts occurs as the 1st presenting sign. Screen all family members early to prevent hearing loss.

Question 10

What are the clinical findings of achondroplasia?

Answer 10

Answer
Disproportionately short stature with rhizomelic shortening
Lumbar lordosis
“Trident” hands
Macrocephaly
Flat nasal bridge, prominent forehead, and midfacial hypoplasia
Explanation
Note the hands have a “trident” appearance—hands are short and fingers are quite broad, with digits 3 and 4 splayed more distally than proximally. Growth curve at birth is on track, but by 2–3 months of age the length of these children has fallen to < 5th percentile. They do not have other malformations and are of normal intellect.

Question 11

You are evaluating a 4-year-old boy with the following findings:

Intellectual disability
Large head
Long face with large ears
Large hands and feet
Hyperextensible joints
What is the most likely diagnosis?

Answer 11

Answer
Fragile X syndrome
Explanation
This disease is caused by an unstable cytosine-guanine-guanine repeat in the FMR1 gene on the X chromosome. It occurs in 1 in 4,000 males and 1 in 6,000–8,000 females. This syndrome exhibits features not normally seen in X-linked disorders: 30% of carrier females have a similar clinical phenotype to affected males, and a normal phenotypic male could transmit the gene to his daughters, who subsequently have a 50% risk of having an affected male.

Question 12

What is the most common cardiac finding in an infant with tuberous sclerosis?

Answer 12

Answer
Cardiac rhabdomyomas
Explanation
Cardiac rhabdomyomas are seen in nearly 50% of infants with tuberous sclerosis, but these generally regress over time. They can lead to cardiac outflow obstruction or cardiac arrhythmias.

Question 13

A 15-year-old presents with current findings or history of the following:

Ectopia lentis (dislocated lens)
Aortic dilation found on echo
High-arched palate
Pectus carinatum
Mitral valve prolapse
Normal IQ
What is the most likely diagnosis?

Answer 13

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Answer
Marfan syndrome
Explanation
Marfan syndrome is an autosomal dominant disorder that affects 1/5,000 to 1/10,000 individuals, occurring equally in boys and girls. Be sure you can differentiate Marfan syndrome—normal IQ and upward lens dislocation—from homocystinuria—lower IQ and downward lens dislocation. The Ghent criteria provide a framework for clinical diagnosis.

Question 14

Autosomal dominant inheritance
Bile duct paucity with cholestasis
Pulmonary valve stenosis and peripheral artery stenosis
Posterior embryotoxon
“Butterfly vertebrae”
Triangular face with pointed chin
Long nose with broad midnose
What disorder is associated with these findings?

Answer 14

Answer
20p12 deletion (Alagille syndrome)
Explanation
Alagille syndrome is caused by absence or mutation of the JAG1 gene. Hepatic involvement presents in the first 6 months of life with jaundice, pruritus, and cholestasis. The posterior embryotoxon is a developmental anomaly marked by a prominent white ring of Schwalbe and iris strands that partially obscure the chamber angle. The most common cardiac manifestations are peripheral and branch pulmonic stenoses (67% of patients) and tetralogy of Fallot (7–16% of patients).

Question 15

A newborn presents with the following:

Mandibular and maxillary hypoplasia
Zygomatic arch clefts
Ear malformations that include microtia on one side and atresia on the other side
Downward-slanting palpebral fissures
Colobomata of the lower eyelids
Conductive hearing loss
What is the most likely diagnosis?

Answer 15

Answer
Treacher Collins syndrome (a.k.a. mandibulofacial dysostosis)
Explanation
Treacher Collins syndrome (a.k.a. mandibulofacial dysostosis) is a rare autosomal dominant congenital disorder that affects the development of bones and other tissues of the face. The signs and symptoms of this disorder vary greatly. They range from almost unnoticeable to severe. It is a common exam question and a common choice as a distractor.

Question 16

A 4-year-old presents with the following:

Jerky movements
Hypotonia
Fair hair
Midface hypoplasia
Prognathism (large chin and mandible)
Inappropriate bouts of laughter
Severe intellectual disability
What is the most likely diagnosis?

Answer 16

Answer
Angelman syndrome (maternally derived 15q11–13 deletion)
Explanation
Jerky movements are the classic finding of Angelman syndrome. Remember that this comes from the mother most often as a microdeletion of 15q11–13—as compared to Prader-Willi syndrome, which is derived from the father. Other mechanisms include uniparental disomy, methylation abnormalities, or point mutations.

Question 17

A 4-year-old presents with the following:

History of severe hypotonia at birth
Short stature
Small hands and feet
Hypogonadism
Mild intellectual disability
Obesity
What is the most likely diagnosis?

Answer 17

Prader-Willi syndrome (paternally derived 15q11–13 deletion)
Explanation
Prader-Willi syndrome is most often due to paternally derived microdeletion of 15q11–13. This is in contrast to maternally derived deletion of the same area, which causes Angelman syndrome. Other mechanisms include uniparental disomy and methylation abnormalities.

Question 18

Name common gastrointestinal diseases associated with trisomy 21 (a.k.a. Down syndrome).

Answer 18

Duodenal atresia, Hirschsprung disease, celiac disease, imperforate anus, gastroesophageal reflux disease
Explanation
These diseases occur in up to 10% of infants with trisomy 21. Look for the classic double-bubble sign, indicating duodenal atresia, on abdominal x-rays.

Question 19

If a 10-year-old presented with 1 of the following:

≥ 2 hemangioblastomas in the cerebellum or retina
or

1 hemangioblastoma plus 1 of the following:
Pheochromocytoma
Endolymphatic sac tumors
Kidney/pancreatic cysts
Renal cell carcinoma
Pancreas involvement, neuroendocrine tumors
What would be the most likely diagnosis?

Answer 19

Answer
von Hippel-Lindau (VHL) syndrome
Explanation
VHL syndrome is a highly penetrant autosomal dominant multisystem cancer disorder that presents with benign and malignant tumors of the eyes, CNS, kidneys, pancreas, adrenal, and reproductive glands. The most classic presentation is a cerebellar hemangioblastoma in adolescence or retinal angioma by 10 years of age.

Question 20

A 15-month-old presents with:

Macrodactyly
Soft tissue hypertrophy
Hemihypertrophy (hemihyperplasia)
Lymphangiomas
Hemangiomas
Accelerated growth
What is the most likely diagnosis?

Answer 20

Proteus syndrome
Explanation
Proteus syndrome is classic for accelerated growth with hemihypertrophy. Do not confuse this with Beckwith-Wiedemann syndrome, which also is associated with hemihypertrophy. Beckwith-Wiedemann syndrome also has cryptorchidism and ear lobe creases/posterior auricular pits to help you distinguish it. In addition to the listed features, Proteus syndrome has lipomas and nevi.

Question 21

A newborn presents with a disruptive cleft of her face and palate, as well as apparent amputation of her 4th and 5th digits on her left hand.

What is the likely etiology?

Answer 21

Amniotic band sequence
Explanation
Amniotic band sequence presents with disruptive clefts of the face and palate resulting from amniotic bands adhering to this area. Bands can also form in other parts of the fetal body. Other defects can include constriction rings of the limbs and/or digits; amputations are common. Most cases are sporadic without a known genetic cause.

Question 22

A 12-year-old presents with the following:

Ash-leaf spots (hypopigmented macules) that enhance with Wood lamp
Oval-shaped nevoid plaque that is skin-colored, smooth, and appears on the lower back
Facial angiofibromas
Forehead plaques
Nail fibromas
Cortical tubers and subependymal nodules
Renal angiomyolipomas
History of polycystic kidney disease
What is the most likely diagnosis?

Answer 22

Answer
Tuberous sclerosis
Explanation
Tuberous sclerosis is an autosomal dominant disorder with the features outlined that may affect 1/6,000 people. The “ash-leaf spots” are the most common presentation, appearing in ~ 90% of cases. The “oval-shaped nevoid plaque” is a shagreen patch. Tuberous sclerosis has multiple, varied presentations, even within families. Infants may lose some of their characteristics by adulthood. Infantile spasms is also an associated finding.

Question 23

A newborn presents with the following:

Brachycephaly
Frontal bossing
Wormian bones (abnormal intrasutural bones)
Hypoplastic/absent clavicles
Joint laxity
What is the most likely diagnosis?

Answer 23

Answer
Cleidocranial dysostosis
Explanation
In addition to these findings, there is delayed eruption of deciduous and permanent teeth. It is common to have supernumerary and fused teeth as well.

Question 24

You diagnose a child with trisomy 18.

What is the most likely cardiac abnormality?

Answer 24

Answer
Ventricular septal defect
Explanation
90% of children with trisomy 18 have a structural heart defect. Most often this is a ventricular septal defect with multiple dysplastic valves.

Question 25

A 10-year-old presents with the following:

Multiple café au lait spots
Freckling of the axilla and inguinal areas
Optic glioma
3 iris hamartomas (Lisch nodules)
Sphenoid dysplasia
History of learning disorder
What is the most likely diagnosis?

Answer 25

Answer
Neurofibromatosis Type 1 (NF1)
Explanation
NF1 is an autosomal dominant disorder that affects ~ 1/3,000. It is the most common neurocutaneous disease. Clinical diagnosis requires 2 of the following:
= 6 café au lait macules = 5 mm in diameter in prepubertal individuals and = 15 mm in diameter in postpubertal individuals
= 2 neurofibromas of any type or = 1 plexiform neurofibroma
Freckling in the axillary or inguinal region
= 2 Lisch nodules (iris hamartomas)
Optic glioma
Sphenoid dysplasia or thinning of the long bone cortex, with or without pseudoarthrosis
1st degree relative (parent, sibling, or offspring) with NF1

Question 26

A pedigree has the following characteristics:

Only females can transmit the disease to their sons; there is never male-to-male transmission.
If a generation has only females, the disease will appear to “skip” that generation.
An affected father transmits the disease allele to all of his daughters (the daughters are obligate carriers) but they are typically unaffected.
What is the most likely classic Mendelian inheritance pattern?

Answer 26

X-linked recessive
Explanation
X-linked recessive disorders generally affect males only; hemophilia A, Duchenne muscular dystrophy, and Becker muscular dystrophy are classic examples. Some female carriers of X-linked diseases may be affected depending on X-inactivation.

Question 27

A 3-year-old presents with the following:

Blue sclerae
Delayed fontanelle closure
Hyperextensible joints
Hearing loss
History of 3 fractures (all recently)
What is the most likely diagnosis?

Answer 27

Osteogenesis imperfecta (OI) Type 1
Explanation
OI Type 1 (classic nondeforming OI with blue sclerae) is an autosomal dominant disease that is also known as “brittle bone disease.” Fractures rarely occur at birth but are frequent in childhood, especially with even minor trauma. Type 1 is the mildest and most common type of OI. It is caused by a decrease in synthesis of Type 1 collagen.

Question 28

A 1-month-old presents with the following:

Hypotonia
Small ears
Brachydactyly
High-arched palate
Speckled irises
Upslanted palpebral fissures
Epicanthal folds
Single transverse palmar crease
Hypoplasia of the middle phalanx of 5th finger
What is the most likely diagnosis?

Answer 28

Trisomy 21 (a.k.a. Down syndrome)
Explanation
Trisomy 21 is the most common autosomal chromosome trisomy and occurs in 1/800 live births. ~ 95% have 3 copies of the whole chromosome 21, with the remainder having an extra part of the long arm or mosaicism. Increasing maternal age is the only known risk factor.

Question 29

A newborn presents with the following:

Glossoptosis (downward displacement of the tongue)
Micrognathia
Cleft palate
Respiratory distress
Feeding difficulties
What is the likely diagnosis?

Answer 29

Pierre Robin sequence
Explanation
Pierre Robin sequence presents with a primary embryologic defect of the mandible, which leads to displacement of the tongue, interrupted closure of the lateral palatine ridges, and a U-shaped cleft palate. These children have small jaws, hence their tongues commonly appear to be too large for their mouths.

Question 30

A newborn presents with the following:

Soft skull
Short, bowed limbs
X-rays of long bones show a “crumpled appearance.”
Ribs are beaded with callus formation.
Multiple fractures
What is the most likely diagnosis?

Answer 30

Answer
Osteogenesis imperfecta (OI) Type 2
Explanation
OI Type 2 (perinatally lethal OI) is the most severe form and results in death during the newborn period due to respiratory insufficiency. Unlike in OI Type 1, fractures occur very early in Type 2, with reports of in utero fractures. Almost all cases are due to de novo autosomal dominant mutation of the COL1A1 gene, which disrupts Type 1 collagen formation.

Question 31

What is CHARGE syndrome?

Answer 31

Coloboma
Heart defects
Atresia of the choanae
Restricted growth and development
Genital anomalies (hypogonadism)
Ear anomalies and/or deafness
Explanation
CHARGE syndrome results from autosomal dominant mutations in the CHD7 gene on chromosome 8q

Question 32

A newborn presents with the following:

Craniosynostosis with brachycephaly
Hypertelorism
Strabismus
Narrow palate (“cathedral ceiling”)
Syndactyly
“Single nails”
Broad thumbs
What is the most likely diagnosis?

Answer 32

Answer
Apert syndrome
Explanation
Apert syndrome is an autosomal dominant disorder with these features. “Single nails” refers to the mitten-hand deformity—common with this disorder—in which 2, 3, or 4 fingers are completely fused with a common nail bed.

Question 33

A 12-year-old presents with the following:

Hyperextensible skin
Hypermobile joints
Dystrophic scarring
Skin texture is like “wet chamois.”
Wrinkled palms and soles
Mitral valve prolapse and/or proximal aortic dilatation
Easy bruising; coagulation tests (PT, aPTT, bleeding time) are normal except for capillary fragility testing, which is abnormal.
What is the most likely diagnosis?

Answer 33

Ehlers-Danlos syndrome
Explanation
Ehlers-Danlos syndrome is a group of autosomal dominant connective tissue disorders that include 6 major variants. Joint hypermobility is common but may not appear in all types. Wrinkled palms and soles are common. The skin findings are classic!

Question 34

Which type of craniosynostosis is the most common?

Answer 34

Sagittal synostosis
Explanation
Craniosynostosis is the early, pathologic fusion of calvarial sutures. Sagittal synostosis is the most common single-suture fusion, followed by coronal, metopic, and the very rare isolated lambdoid. Sagittal synostosis is more common in males by a ratio of 5:1.

Question 35

You diagnose a child with Williams syndrome.

What is the most likely cardiac defect?

Answer 35

Answer
Supravalvular aortic stenosis
Explanation
This is the classic cardiac defect in Williams syndrome. It occurs in 45–75% of patients. Know it!

Question 36

A newborn girl presents with the following:

Intrauterine growth restriction
Microcephaly
Small face and mouth
Rocker bottom feet
Clenched fist
Hypoplastic nails
What is the most likely diagnosis?

Answer 36

Answer
Trisomy 18 (Edwards syndrome)
Explanation
Trisomy 18 is the 2nd most common autosomal trisomy. It occurs in ~ 1/6,000 live births, with a much higher incidence of stillbirths. Girls are more commonly affected than boys by a ratio of 4:1.

Question 37

Absence of which 2 genes may result in WAGR syndrome?

Answer 37

PAX6 and Wilms tumor 1 (WT1)
Explanation
Remember that WAGR syndrome is associated with:

Wilms tumor
Aniridia
Genitourinary malformation
Reduced intellectual abilities
Phenotypically, these children have a long face with poorly formed ears, upward-slanting palpebral fissures, ptosis, and a beaked nose.

Question 38

A newborn presents with the following:

Intrauterine growth restriction
Hirsutism
Downturned mouth
Micrognathia
Low hairline
Long eyelashes
Thin upper lip
Cardiac defects
Micromelia (hands/feet)
2,3 syndactyly of toes
What is the most likely diagnosis?

Answer 38

Cornelia de Lange syndrome
Explanation
Cornelia de Lange syndrome is a very rare autosomal dominant disorder with > 50% resulting from a new mutation of the NIPBL gene. This is one of the classic short stature syndromes. Hirsutism and micromelia help differentiate this from other disorders.

Question 39

A newborn presents with the following:

Disproportionately short stature with rhizomelic shortening
Trident hands
Macrocephaly
Flat nasal bridge
Prominent forehead
Midfacial hypoplasia
What is the most likely diagnosis?

Answer 39

Achondroplasia
Explanation
Achondroplasia is the most common skeletal dysplasia and occurs in 1/20,000 live births. It is an autosomal dominant disorder, with most individuals having a de novo mutation of FGFR3 (fibroblast growth factor receptor 3) on chromosome 4p16.3.

Question 40

A 1-year-old presents with the following:

White sclerae
History of fractures at birth
Tibial bowing
Delayed fontanelle closure
What is the most likely diagnosis?

Answer 40

Osteogenesis imperfecta (OI) Type 4
Explanation
OI Type 4 (common variable OI with normal sclerae) is a milder form, like Type 1. Type 4, though, has white sclerae (not blue as in Type 1). Tibial bowing is the hallmark of Type 4.

Question 41

An infant presents with infantile spasms.

The infant has a 50% risk of having what genetic condition?

Answer 41

Answer
Tuberous sclerosis
Explanation
It is helpful to look at an infant who is experiencing infantile spasms with a Wood lamp. This enhances the ash-leaf spots (hypopigmented macules) that occur in ~ 90% of cases of tuberous sclerosis, helping to make an earlier diagnosis.

Question 42

A newborn presents with the following:

Midline cleft lip
Microphthalmia
Postaxial polydactyly of the limbs
Holoprosencephaly
Absent ribs
Aplasia cutis congenita
What is the most likely diagnosis?

Answer 42

Trisomy 13 (Patau syndrome)
Explanation
Trisomy 13 (Patau syndrome) is the 3rd most common autosomal trisomy and occurs in ~ 1/20,000–1/25,000 live births. Median survival is 2.5 days. Think midline defects for this trisomy!

Question 43

WAGR syndrome is characterized by which 4 abnormalities?

Answer 43

Wilms tumor
Aniridia
Genitourinary (GU) malformation
Reduced intellectual abilities
Explanation
WAGR syndrome results from a deletion of the short arm of chromosome 11 (11p13 deletion). Wilms tumor occurs in up to 50% of cases, most often by 3 years of age. The GU abnormalities are generally male genital hypoplasia (e.g., hypospadias, cryptorchidism). These patients are at increased risk of gonadoblastoma as well.

Question 44

A newborn presents with:

Macrocephaly
Prominent forehead
Hypertelorism
Large hands/feet
Large for gestational age
What is the most likely diagnosis?

Answer 44

Sotos syndrome
Explanation
Sotos syndrome is an extremely rare autosomal dominant growth abnormality disorder. It presents as a very large-appearing child with these findings. 80–90% of cases are caused by mutation of the NSD1 gene.

Question 45

Which endocrine disorder should be screened for at 6 and 12 months of age in a child with trisomy 21 (a.k.a. Down syndrome)?

Answer 45

Answer
Hypothyroidism
Explanation
After the 1st year of life, annual screening should occur for hypothyroidism. Other concerns include vision issues, hearing loss, celiac disease, atlantoaxial instability, and leukemia. Later in life, patients need to be monitored for Type 2 diabetes, hyperthyroidism, cataracts, seizures, cognitive dysfunction, and dementia or early-onset Alzheimer disease.

Question 46

A child presents with the following:

Partial albinism
White forelock
Premature graying
Iris heterochromia
History of cleft lip
Cochlear deafness
What is the most likely diagnosis?

Answer 46

Waardenburg syndrome I
Explanation
Waardenburg syndrome I is an autosomal dominant disorder. It is occasionally associated with Hirschsprung disease. Affected girls can be born without a vagina.

Question 47

A newborn presents with the following:

Numerous fractures
Severe short stature
Blue sclerae
Hydrocephalus
Basilar skull invagination
What is the most likely diagnosis?

Answer 47

Osteogenesis imperfecta (OI) Type 3
Explanation
OI Type 3 (progressively deforming OI) presents in the newborn with numerous fractures like OI Type 2. The sclerae are blue at birth but become lighter with age (unlike those in OI Type 1, which stay dark blue). Neurologic complications (hydrocephalus and basilar skull invagination) are most common with OI Type 3.

Question 48

Cleft palate
Thymus agenesis or hypoplasia
Parathyroid gland agenesis or hypoplasia
Hypoplasia of the auricle and external auditory canal
Tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, or truncus arteriosus
Short stature
Behavioral problems
What syndrome is characterized by these findings?

Answer 48

Answer
22q11.2 deletion (a.k.a. DiGeorge syndrome)
Explanation
22q11.2 deletion syndrome includes phenotypes referred to as DiGeorge syndrome or velocardiofacial syndrome. CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft defects, hypocalcemia, chromosome 22) is a mnemonic that is not used clinically; however, it is helpful for exams! 22q11.2 deletion is the most prevalent microdeletion syndrome with ~ 1/6,000 live births affected.

Question 49

A boy presents with the following:

Webbed neck
Short stature
Pulmonary valve stenosis
Pectus excavatum
Hypertelorism
Lymphedema
What is the most likely diagnosis?

Answer 49

Answer
Noonan syndrome
Explanation
Think of Noonan syndrome in a boy or girl with pulmonary valve stenosis and a webbed neck. Noonan syndrome is an autosomal dominant disorder. Children with this disorder may also have bleeding diathesis.

Question 50

You are given a pedigree on the test with the following characteristics:

Both sexes are equally affected.
Both sexes can transmit to offspring.
No generation is skipped.
You see father-to-son transmission.
What is the most likely classic Mendelian inheritance pattern?

Answer 50

Answer
Autosomal dominant (AD)
Explanation
Remember that AD disorders are expressed with only 1 copy of an altered allele. A heterozygous parent has a 50% chance of passing the disorder to their children. Father-to-son transmission excludes all X-linked and mitochondrial transmissions! Neurofibromatosis Type 1 is a classic example. Note that spontaneous new mutations are common—it is possible that prior generations were unaffected.

Question 51

What is VATER/VACTERL association

Answer 51

Vertebral,
Anal atresia,
Cardiac,
Tracheal,
Esophageal,
Renal, and
Limb defects
Explanation
VATER/VACTERL association is a common exam question, so be sure you know what the acronym stands for. Also know that it is an association of findings—not a syndrome.

Question 52

A newborn presents with the following:

Branchial cleft fistulas or cysts
Preauricular pits
Cochlear and stapes malformation
Hearing loss
Renal dysplasia/aplasia
What is the most likely diagnosis?

Answer 52

Answer
Branchio-oto-renal (BOR) syndrome
Explanation
BOR syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. Occasionally, patients have pulmonary hypoplasia. It is inherited as an autosomal dominant disorder.