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Flashcards in Genetics Deck (193):

When can amniocentesis be done?

16 weeks


What is used to track intrauterine growth over time?

Fetal US


When are structural anomalies (like myelomeningocele) best detected on US?

Between 12-24 weeks gestation


What maternal problem can be a complicating factor that blunts the accuracy of US findings?

Maternal obesity


What 3 hematologic diseases can be diagnosed prenatally?

Factor 8 deficiency, factor 9 deficiency, sickle cell disease


What is monogenic inheritance?

Genetic disorders caused by a mutation in one gene


What is multifactorial inheritance?

Genetic disorders caused by mutations in multiple genes


What is epigenetics?

Genetic disorders caused by a combination of gene mutations and environmental factors


In which inheritance pattern are males affected and females carriers?

X-linked recessive


If there are any female relatives with a disorder, which inheritance pattern is eliminated?

X-linked recessive


Is male-to-male transmission possible in X-linked recessive disorders?



If a question casually mentions a kid who had two uncles with a similar problem, what should you think?

You know that only males are affected...pointing towards an X-linked recessive disorder


Which type of inheritance disorders frequently involve an enzyme deficiency?

X-linked recessive


Name 8 frequently tested X-linked recessive conditions

1. Hemophilia A/B: Factor 8/9 enzyme deficiencies
2. G6PD Deficiency: Enzyme deficiency
3. CGD: Enzyme to break down bacterial cells in neutrophil is defective
4. Duchenne Muscular Dystrophy
5. Nephrogenic Diabetes Insipidus: Enzyme deficiency
6. Retinitis Pigmentosa: Enzyme deficiency
7. Androgen Insensitivity (Testicular Feminization): Enzyme defective
8. Wiskott Aldrich Syndrome


When will you see a phenotypic female, but genetic male and what is the inheritance pattern of this disorder?

Androgen insensitivity (X-linked recessive)


Mom is known carrier of an X-linked recessive disorder...chances of affected male, female carrier, affected children?

Males: 50% affected, 50% not affected
Females: 50% carriers, 50% not carriers
Children: 25% carriers, 25% disease, 50% normal


For X-linked dominant disorder, Dad has gene on his X chromosome, which kids have disease?

-Only has affected X to give to daughters...all daughters will have disorder
-Only has Y to give to sons...none of his sons will have disorder


For X-linked dominant disorder, Mom has gene on one of her X chromosomes, which kids affected?

50% of her kids will have it and 50% won't


Are there carriers for an X-linked dominant disease?



Which other inheritance pattern is the same as X-linked dominant?

Autosomal dominant...makes it very difficult to distinguish


How are mitochondrial disorders transmitted?

Exclusively through mothers

*Mother and mitochondria both start with an M


Which disorders have no male to male transmission?

X-linked disorders (recessive or dominant)


Name 4 X-linked dominant conditions to consider (remember, not too many of them and they will most likely not ask you to pick this up from question)

1. X-linked hypophosphatemic rickets
2. Pseudohyperparathyroidism
3. Aicardi syndrome
4. Alport syndrome


What is the only way a disease can be transmitted from father to son?

Autosomal dominant inheritance


What are 3 characteristics of autosomal dominant disorders?

1. Variable expressivity
2. Possible reduced penetrance
3. High risk for spontaneous mutation with no prior family history


What is the mneumonic for 8 of the autosomal dominant diseases?

Tuberous Sclerosis
Marfan Syndrome
Apert, All porphyrias (occasionally Alport syndrome)
Nail Patella Syndrome, Neurofibromatosis

*Neurofibromatosis can have variable expressivity with a high spontaneous mutation rate


What 2 things are autosomal dominant disorders associated with?

1. Variable penetrance
2. Variable expressivity


What is variable penetrance?

When there is variability of whether people with the gene for a given trait actually exhibit it


When can chorionic villus sampling be done?

12 weeks


What is variable expressivity?

Range of signs and symptoms that can occur in different people with the same genetic condition...basically a mixed bag of features can be seen in people with a given syndrome with wide variable expressivity.


What rules out an autosomal recessive disorder?

Vertical transmission through 3 generations


Mneumonic for common autosomal recessive conditions?

Receding because you go to get gas from a guy wearing a hat, but he gives you a wak on the hand with a pickax...
Alpha 1-Antitrypsin Deficiency
Sickle cell and Thalassemia
Hurler syndrome
Ataxia Telangiectasia
Tay Sachs Disease
Wilson Disease
Adrenogenital Syndrome (and Alpers Syndrome)
Kartagener Syndrome


In an autosomal recessive condition, what percent of unaffected offspring are carriers?



What is genetic anticipation?

Altered gene is passed down from one generation to next...disorder may begin earlier in life and signs and symptoms become more severe in subsequent some cases, this happens because there is an increase in the length of the unstable region in the gene

Ex: Myotonic dystrophy


Webbed neck, delayed secondary sexual characteristics, left sided congenital heart defects (bicuspid aortic valve, coarctation of aorta), short 4/5th metacarpal bones, widely spaced nipples, lymphedema of hands and feet

Turner syndrome (Primary Gonadal Dysgenesis)


Is Turner Syndrome associated with advanced maternal age?

No (since it isn't a trisomy)


What are some features of Turner Syndrome in an adolescent?

Short stature, minimal/no breast development, primary amenorrhea, wide carrying angle of elbows, chronic otitis media, hyperconvex nails, low hairline, small mandible, high arched palate, low set ears


What causes Turner Syndrome?

Full or partial X chromosome deletion (in addition to phenotypical features outlined above)


Can a male get Turner Syndrome?

No, Turner Syndrome can only be diagnosed in a female


What is the most common chromosomal defect discovered in spontaneous abortions, and what is the most common form?

Turner Syndrome, 45XO


What is necessary for definitive diagnosis of Turner Syndrome?

Karyotype...buccal smear is not correct


If you think someone has Turner Syndrome and the initial chromosome analysis is normal, what should you do?

Use a FISH study to look for mosaicism (remember, elevated FSH can also be a feature of Turner Syndrome)


What has been used to treat short stature in Turner Syndrome?

Growth Hormone


What used to be known as "Male Turner Syndrome"?

Noonan Syndrome


Who can get Noonan Syndrome?

Males and females


4 classic features of Noonan?

Pertussis excavatum
Webbed neck
Low set ears
Pulmonic stenosis

*Envision a moon man pulling a web neck and grabbing the moon and placing it on his chest, snugly on the pectus excavatum. The moon changes tide on his chest and pulls down the ears, and also exerts pressure on the heart, resulting in pul"moonic" stenosis


What is the karyotype in Noonan? identifiable genetic patterns, although genetics do play a role


Describe eye issues with Noonan Syndrome

Hypertelorism, downslanting, vivid blue or blue-green irides, epicanthal folds, thick/droopy lids, strabismus/amblyopia


What are the two cardiac defects with Noonan Syndrome?

Pulmonary valve stenosis (number 1) and hypertrophic cardiomyopathy


Deeply grooved philtrum, short and webbed neck, low posterior hairline, unusually-shaped chest with superior pectus carinatum and inferior excavatum, developmental delay or MR of variable degree, joint laxity, cryptorchidism, coarse/curly hair, short stature, inverted triangular facies, low set ears, posteriorly rotated ears, fleshy helices on ears, high frequency SNHL, variable coagulation defects, male: female is 1:1

Noonan Syndrome


What is the inheritance of Marfan syndrome?

Usually autosomal dominant (15% of cases are a new mutation)

*There can be great variation of the morphology among affected family members


Connective tissue disorder associated with skeletal, cardiac, and ophthalmologic manifestations.

Marfan Syndrome


Where is the mutation in Marfan?

Chromosome 15 (fibrillin gene)


What are the skeletal abnormalities with Marfan!

Tall stature, high arched palate, dental crowding, hyperextensible joints, pectus abnormalities, arachnodactyly, disproportionately long extremities compared to the trunk


Is mitral valve prolapse one of the amour criteria?



What murmurs will you see with Marfan Syndrome?

Aortic or mitral valve regurgitation


Tall teenager presenting with a spontaneous pneumothorax...?

Marfan Syndrome


What are patients with Marfan syndrome at risk for that can lead to death?

Sudden death associated with aortic rupture...close cardiac followup is important (referral of other family members for genetic testing would be appropriate)


What are the 5 major criteria for diagnosing Marfan?

1. Dilatation or dissection of the ascending aorta/aortic root
2. Lumbosacral dural ectasia
3. Ectopia lentis
4. Four skeletal manifestations
5. Family or genetic history


How do you tell apart Marfan and Homocystinuria?

The body type is similar for both...but in homocystinuria the lens is usually displaced downwards (Marfan the lens is displaced up)


What 2 things is homocystinuria associated with?

Mental retardation and thrombosis


What is wrong with the eyes in Marfan?

Ectopia lentis (upward and temporal displacement of the lens of the eye)


What type of exams are important for Marfans (for the eyes)?

Serial slit lamp evaluations


What are the only genetic disorders that increase with advancing maternal age?

Trisomies (incidence of all trisomies increases with advancing maternal age)


From what 2 things can trisomy 21 arise?

1. Nondisjunction
2. Translocation

*No phenotypic differences between the two, but genetic implications quite different


In which cause of trisomy 21 are chromosomal studies of the parents crucial?



If you find a carrier parent with a full translocation for trisomy 21, what is the chance of Down syndrome reoccurring?

100% chance (but this is extremely rare)


With a partial translocation for trisomy 21, what is the % chance for Downs recurring and which side carries a higher risk?

Close to 15%...if partial translocation is from Mom, chances of recurrence are higher than if from Dad


What is the risk for recurrence of Downs with nondisjunction?

Risk for recurrence equals overall risk for general population (1%) plus Mom age related risk


What is the age related risk for trisomy 21 with mom at age 22? At age 40?

22: 1/1500
40: 1/90


What is the only truly useful test for detecting conditions of a missing or extra chromosome? (Turner or Downs)



What chromosomal abnormalities will karyotyping miss?

Small changes in a chromosome


What is the gold standard genetic test for detecting small losses or gains in chromosomes?

Array comparative genomic hybridization (array CGH)


What test is widely used in evaluation of intellectual disability or congenital malformations?

Array comparative genomic hybridization (array CGH)


What do people with balanced translocation look like, and what are their offspring like?

Appear normal, often have offspring with a genetic condition


What do people with unbalanced translocations look like and what do their offspring look like?

Have a genetic condition, always have offspring with a genetic condition


Which age group gives birth to more infants with Down Syndrome?

Mothers in their 20s (more women in their twenties have kids, period)


Which age group is at a greater risk for having a child with Down syndrome?

Women in their 40s are at a greater risk for having babies with Down Syndrome


What is the most common abnormality seen in Down syndrome and what 2 things does this play a role in with the condition?

Hypotonia (seen in 80% of cases)... May play a role in feeding difficulties and constipation


Features of trisomy 21 (most can be identified in newborn period)..

Down Syndrome

Dysplasia of the middle phalanx of the 5th finger
Ouch! Cardiac disease
Wide gap between the 1st and 2nd toe
Neck has excess skin in the back

Spots (Brushfield spots in the eye)
Y protruding tongue
Nice simian crease (can occur in general population)
Duodenal atresia (Hirshsprung disease)
Really extensible joints
Oncology/leukemia risk
Moro reflex is incomplete
Ears are small and anomalous


What bone do kids with Down syndrome sometimes have missing?

12th rib (12 is 21 backwards...21 chromosome in place of 12 rib)


What can be wrong with EKG for Down syndrome kids and what causes this?

Axis...AV canal (endocardial cushion defect) throws off axis...might refer to it as "NW axis"


Kids with Down syndrome are at increased risk for what 3 things?

1. Leukemia
2. Duodenal atresia
3. Cardiac disease (AV canal/endocardial cushion defect)


What should you be concerned about when doing a sports physical on a patient with Down syndrome who wants to participate in Special Olympics?

Atlantoaxial instability (kids with Down syndrome at particular risk for this)


Features of trisomy 18 (Edward syndrome)?

Clenched fist, rocker bottom feet, hypoplastic nails, prominent occipital, low set ears, horseshoe kidney, overlapping of the index finger over the 3rd, 4th, or 5th digits

*Picture an 18 year old at a rock concert. He has clenched fists and rocker bottom feet. His fists have been clenched for days so he has hypoplastic nails. He's been drinking a lot and rocking back and forth and banging his head on the wall. He gets a prominent occiput and low set ears. He's too busy to go to the bathroom so his kidneys get bent out of shape into horseshoes.


Which genetic disorder gets punched out scalp lesions?

Trisomy 13 (Patau Syndrome)


Features of trisomy 13?

Number 13 is "bad luck"

Brain: Holoprosencephaly, Microcephaly, mid scalp lesions
Airs: Low set ears
Digits: Polydactyly (extra digits)
Leukocytes: Unique nuclear projections in the neutrophils
Uterus: Bicornuate uterus and hypoplastic ovaries
Cleft Lip and Palate: Bilateral
Kidneys: Cystic


Teen who is infertile with small testes, but otherwise normal. Socially awkward with normal intelligence.

Klinefelter syndrome


3 buzz words for Klinefelter syndrome?

1. Delayed speech
2. Poor self image
3. Mild motor delay


Chromosomal issue with Klinefelter syndrome?

47 XXY


Why is genetic testing indicated after the birth of any child with a trisomy?

Because the birth of any trisomy increases the risk of having another child with other anomalies


What are the only 3 trisomies that make it to term?

13, 18, 21


Do trisomies with lower or higher numbers cause more problems?

Lower numbers...since chromosomes with lower numbers are larger than those with higher numbers, the consequences of these trisomies increase as their numbers decrease

*Means that trisomy 21 isn't as bad as trisomy 18 which isn't as bad as trisomy 13


Kid with delayed motor and language development, tall, arms and legs longer than expected for height, 4 cafe-au-lait spots between 4-5mm each, loner, calm most appropriate diagnostic step?

Chromosome analysis...history most consistent with Klinefelter syndrome

*Don't be fooled with neurofibromatosis because of cafe-au-lait spots. 6 or more measuring at least 5mm is consistent with neurofibromatosis. Don't let long arms and legs make you think Marfan


What are weight, head circumference, and height for Klinefelter syndrome?

Weight and head circumference should be normal. Height can be well above average.


What is the problem with the testicles I'm Klinefelter?

They are small...the German word for small is Klein


What is one treatment option for Klinefelter?

Testosterone supplementation


What happens when chromosomal regions with similar (95-99%) sequences cause misalignment of homologous chromosomes, leading to either deletions or duplications of those similar regions?

Contiguous gene malformations


How are common contiguous gene deletions and duplications best diagnosed?

Fluorescence in situ hybridization (FISH)

You MUST specify the suspected diagnosis


Neonatal hypotonia, failure to thrive as infant, voracious appetite starting about 2-3, obesity, intellectual disability, small testicles, small hands and feet?

Prader-Willi Syndrome


What causes much of the morbidity and mortality in kids with Prader-Willi syndrome?

Complications of obesity...diabetes, sleep apnea, slipped capital femoral epiphysis


How does pseudo hypogonadism present and what is the tip off?

Genitalia are normal sized, but the body is big in comparison...tip off could be significant gynecomastia


When are kids with Angelman syndrome usually diagnosed?

Between 3 and 7


Severe developmental delay, profound speech impairment, ataxia and other movement disorders, behavioral anomalies (frequent laughter, easy excitability, short attention span), acquired microcephaly, seizures

Angelman syndrome


Why are kids with Angelman syndrome called happy puppets?

Combination of laughing and abnormal jerky movements


What type of gene malformation is neurofibromatosis 1?

Contiguous gene malformation


What 2 syndromes represent the gene error 15q11-13

Prader-Willi and Angelman


If you have 2 copies of 15q11-13 from mom (Dad's section is absent) what syndrome do you have?



If you have 2 copies of 15q11-13 from dad (Mom's copy is missing), what syndrome do you have?

Angelman syndrome


What is it when the ability of a gene to be expressed depends upon the sex of the parent who passed on the gene?

Genomic imprinting


Name 7 important features of Beckwith Wiedemann syndrome?

Hypospadias, hypoglycemia, hemihypertrophy, macroglossia, macrosomia, omphalocele


Elfin facies, wide spaced teeth, upturned nose, mild intellectual disability, cocktail party personality (very friendly)

Williams syndrome (think of Robin Williams)


What electrolyte abnormality do you see in kids with Williams syndrome?



What valve issue do kids with Williams syndrome get?

Supravalvular aortic stenosis


What is another name for 22q11 Deletion Syndrome or Velocardiofacial Syndrome?

DiGeorge Syndrome


Hypoplasia of what structures causes the problems in DiGeorge Syndrome?

Thymic and hypoparathyroid hypoplasia


Hypocalcemia, immune deficiencies, conotruncal cardiac defects (like tetralogy of fallot)

DiGeorge Syndrome

(Thymic and hypoparathyroid hypoplasia cause hypocalcemia and immune deficiencies)

(Mutation is highly correlated with conotruncal cardiac ToF)


Fetal alcohol syndrome can be diagnosed with or without confirmed maternal alcohol exposure if what 3 criteria are present?

1. Characteristic facies
2. Deficient brain growth
3. Prenatal and/or postnatal growth retardation

FAS = Facies, Abnormal brain, Small


Describe the characteristic facies with fetal alcohol syndrome.

Flat philtrum (thing in middle of upper lip), thin vermillion border of the upper lip, midface hypoplasia, short palpebral fissures

*Picture a child drinking alcohol...from having the bottle in his mouth so often, it forms a mark on the middle of his face (midface hypoplasia) and thins out his upper lip and philtrum


What is the most common preventable cause of intellectual disability?

Fetal alcohol syndrome

*In addition to intellectual disability, kids with FAS can also have behavioral and psychiatric disorders...even in absence of intellectual disability


What are the 2 most common identifiable genetic causes of intellectual disability?

Fragile X syndrome and Down syndrome (these 2 are not preventable)


What are some things maternal smoking results in?

Low birthweight infants, higher miscarriage rates, placental abruption, placental previa, IUGR, prematurity, cleft lip/palate


What is associated with asthma, wheezing, and other respiratory ailments?

Smoking during pregnancy...independent of maternal smoking after delivery


What issue with Mom is associated with SIDS?

Maternal smoking


What abnormal neurobehavior can result from smoking during pregnancy?

Deficits in mental development, language deficits, ADHD, and lower IQ (this can extend into childhood)


Exposure to anticonvulsants is associated with increased risk for what?

Microcephaly, intrauterine growth retardation, anticonvulsant face (broad bridge of nose, small anteverted nostrils, long upper lip), fingernail hypoplasia, cardiac defects, cleft lip, hypospadias with cryptorchidism, clubfoot deformity


Valproic acid exposure leads to deformities of what?



What issues does carbamazepine cause?

Spinal problems and facial deformities (change name to car-bam and picture an auto accident resulting in spinal problems and facial deformities)


Phenytoin results in a specific profile that includes what?

Finger stiffness and severe nail hypoplasia

Cardiac, skeletal, and ophthalmological anomalies may occur


What 2 anticonvulsants can result in neural tube defects?

Carbamazepine and Valproic acid


What supplementation prior to conception can decrease the incidence of neural tube defects by more than 50%?

Folic acid


Which started out bad v. started out well but met a roadblock and now is bad?

Malformation started out bad

Deformation started out well, but met a roadblock and now is bad


What is the clustering of anomalies that can't be explained by chance?

Association (Examples: CHARGE and VACTER-L)


What is the result of a localized abnormality early in fetal development?


Example would be Potter Syndrome (Oligohydramnios Sequence)...effects all stem from olihohydramnios

Pierre Robin sequence is another example


What is the CHARGE association?

Coloboma/cognitive deficits
Heart disease
Atresia (choanal)
Retarded growth and development
GU abnormalities (genital hypoplasia)
Ear anomalies (hearing loss)


What is the intelligence level in CHARGE syndrome?

Below normal...think of it as since they are mentally challenged, someone else has to be in CHARGE of them


What is the VACTER-L syndrome?

Vertebral defects
Anal atresia
Cardiac defects/VSD
TE fistula
Radial hypoplasia and Renal abnormalities

Limb abnormalities


VACTER-L may be part of what deletion syndrome?



What association often presents with a single umbilical artery?



What is the intelligence with VACTER-L association?



What is the deformation of the skull due to premature fusion of one or more of the sutures?



When does craniosynostosis have to be recognized by?

Before 5 months of age...treatment is more successful when done prior to the period of greatest head growth...craniosynostosis can be easily corrected


What neurological complications are more likely to occur when 2 or more sutures close prematurely?

Hydrocephalus or increased intracranial pressure


What might be confused with craniosynostosis, but has a head CT with normal sutures?

Positional plagiocephaly


What might look abnormal, but is harmless and will improve over time once babies don't spend so much time lying flat on their backs?

Positional plagiocephaly


What is used to treat positional plagiocephaly?

Just time once baby isn't on back so much

Can use helmets, but this isn't the right answer for boards


What causes a small symmetrical head (with respect to suture closure)?

Closure of cranial sutures secondary to slow brain growth


What would present with an asymmetrically shaped head (with respect to suture closure)?

Premature closure of a single cranial suture


What causes a parallelogram head shape (ipsilateral frontal bossing)?

Positional plagiocephaly


What causes a trapezoidal head shape (contralateral frontal bossing)?

Unilateral lamdoid synostosis


What causes dolichocephaly/scaphocephaly (long skinny egg-shaped head)?

Saggital synostosis


What causes brachycephaly (short wide head)?

Bilateral coronal synostosis


What causes trigonocephaly (triangle head)?

Metopic synostosis


What causes cloverleaf skull?

Multiple suture synostosis


What is the cause of olihohydramnios sequence (Potter syndrome)?

Renal agenesis


What is the appearance of an infant with Potter syndrome due to?

Consequences of olihohydramnios


Name the 4 primary features of Potter syndrome

1. Typical facies described as "pugilistic"
2. Hypoplastic lungs
3. Limb malformations (club feet)
4. Renal agenesis


Which condition will you see "glove-like" excess skin on the hands and have fetal membranes covered by yellowish nodules (amnion nodosum)?

Potter Syndrome (oligohydramnios sequence)


Genitourinary anomalies are an important part of the workup for which sequence/syndrome?

Potter syndrome


Kids with Potter syndrome ultimately die of what?

Pulmonary complications


Broad thumb and cryptorchidism

Rubinstein-Taybi Syndrome (think Rubinstein Thumby)

*It is difficult to bring down an undescended testicle with a broad based thumb


Which syndrome has thumbs and great toes that are short and broad with eyes that are prominent and widely spaced?

Pfeiffer syndrome


Which syndrome has eyes that are prominent and widely spaced?

Crouzon syndrome


A kid who looks like a cross between Crouzon and Rubinstein-Taybi likely has what syndrome?

Pfeiffer syndrome


Triangle face (small chin) and growth retardation?

Russell Silver Syndrome (these kids are very small)

*Picture a small (growth retarded) wrestler with a triangle face made of silver


What leads to the prune belly appearance in Prune Belly Syndrome?

Lack of abdominal muscle development


What is the pathophysiology of prune belly syndrome?

Starts with bladder outlet obstruction, which leads to oligohydramnios. This results in pulmonary hypoplasia. The testes are also undescended.


Conductive hearing loss, small jaw, ear abnormalities, lower eyelid abnormalities, no intellectual disability

Treacher Collins

*You can't be a "treacher" with abnormal intelligence


How is Treacher Collins inherited?

Dominant trait...picture a dominating teacher in class

This will occur in several family members (might show a family portrait in which several family members have same dysmorphic features)


One or more family members with a hearing aid could be the tip off to what condition?

Treacher Collins


What movie character do people with achondroplasia look like?

Munchkins from Wizard of Oz


Large heads, very short extremities, rhizomelic shortening, frontal bossing, genu varum (bowlegs), lumbar lordosis (puffed out chest), small foramen magna (can cause nerve root compression), respiratory problems (sleep apnea)



What is known as short-limbed dwarfism, especially of the proximal portion of the limb?



What is rhizomelic shortening?

Shortening of the proximal portion of the limb


What % of kids with achondroplasia have significant sleep apnea?

Over 3/4 of kids (there are frequent respiratory problems)


What does syndactyly refer to?

The union of two or more fingers or toes...typically only involves a skin connection between the two, but can include fusion of bones


What is permanent deviation of one or more fingers, usually the 5th finger (pinky)?



What is the inheritance of achondroplasia?

Autosomal dominant

*Like all autosomal dominant conditions, it has a high rate of spontaneous mutation...this means a child can have it, even when the parents do not


What is the intelligence in achondroplasia?



Macrocephaly, frontal bossing, midface hypoplasia, proximal shortening of the limbs...condition, inheritance pattern, and most likely cause of sudden death in this infant?

Achondroplasia, autosomal dominant, however > 80% of cases occur as a spontaneous mutation, most common cause of sudden death is cervicomedullary junction compression

*Don't believe respiratory and cardiac failure as associations and thus cause of sudden death


Male, mild intellectual disability, positive family history of uncles and other males affected, long narrow face, prominent forehead, protruding ears, high-arched palate, strabismus, hyperflexible joints, weird behavior, macroorchidism

Fragile X Syndrome (think of Prince Charles)


What is the chromosome issue in Fragile X Syndrome?

Repeat of CGG trinucleotide


What is the most common known genetic cause of inherited intellectual disability?

Fragile X


What is the overall second most common cause of genetic intellectual disability, after Down Syndrome?

Fragile X


What is the most common known single-gene cause of autism spectrum disorder?

Fragile X


Which syndrome is genetic, but rarely inherited?

Down syndrome


Can a female get Fragile X syndrome?

Fragile X typically presents in boys, but it can manifest in females (unlikely, but worth considering)


For a kid with intellectual disability who you think might have Fragile X, what type of testing...karyotype or DNA testing?

DNA testing...much more sensitive in diagnosing Fragile X (technically asking for Fragile X Mental Retardation, FMR 1, DNA testing)


Girl around 1-2 who has lost developmental milestones, autistic-like behavior, wringing hands, regression of developmental milestones?

Rett Syndrome

*Picture Rhett Butler (Clark Gable) from Gone with the Wind. Picture him walking backwards, wringing his hands, saying "Frankly my dear, I don't give a damn, which is why I am backing out of the deal."


What is the progression of Rett Syndrome?

Girls have normal development at first, but around 4 months of age their head growth decelerates. Then enter period where they don't continue development (stagnation...usually from 6-18 months), followed by a loss of their milestones (regression...usually from 1-4 years). After this, there is usually no further decline. These children usually survive into adulthood, although they may not gain/regain purposeful hand use or functional speech.


Small chins relative to their tongues, cleft palate, micrognathia, posterior positioning of their tongues, glossoptosis, extremity anomalies (syndactyly, clinodactyly, hip and knee anomalies), spinal deformities (kyphosis and scoliosis), CNS involvement (language delay, seizure, developmental delay)

Pierre Robin Sequence

*Margaret Thatcher...picture her singing like a robin


Why do kids with Pierre Robin sequence have glossoptosis?

Because their tongue is relatively large compared to their small chin...not because they have big tongues...this is an important distinction.


What can lead to cor pulmonale in Pierre Robin Sequence?

Upper airway obstruction caused by glossoptosis