Genetics Flashcards
What are some common facial features of turners syndrome?d
Low hairline, Webbed neck, small mandible, high arched palate and low set ears
What might be the presenting signs of Turner syndrome in an infant?
Short 4th/5th metacarpal bones, wide spaced nipple or lymphedema hands/feet
How might an adolescent with turners syndrome present ?
Short stature, minimal breast development and primary amenorrhea
What cardiac abnormality is associated with turners syndrome?
Bicuspid aortic valve or coarctation
What are the chances of turners syndrome in a woman with advanced age?
The same as the normal palpitation! A chromosome deletion is not associated with advanced maternal age (only trisomys are increased)
How do you diagnose turners and what test is inadequate ?
Need karyotype - if mosaicism, karyotype may be normal but FISH can detect mosaicism
Buccal smear inaccurate
What is the genetic defect in cri du chat?
Deletion of the short arm of chromosome 5
What is the difference between apert syndrome and crouzon syndrome?
Both have craniosynostosis but only apert presents with syndactyly
What features of noonan syndrome differentiate from Turner syndrome?
Noonan syndrome has pectus excavatum and pulmonic stenosis
Karyotype is normal!!
What is the inheritance of crouzon syndrome?
Autosomal dominant
A child presents with craniosynostosis, prominent forehead, proptosis and a beak nose, what syndrome should you consider?
Crouzon syndrome
You are presented with a tall male with small testes who is socially awkward, what should you test for?
Klinefelters - chromosome analysis
Which age group gives birth to the most amount of trisomies?
Women in their 20s
What is the most common abnormality in children with Down syndrome?
Hypotonia
If a mother has a full translocation of chromosome 21, what are the chances her child will have Down syndrome?
100%
If a child has trisomy without translocation of chromosome 21, what are the chances the mother will have another chicks with Down syndrome?
1% plus the age related risk
If an infant had a partial translocation of chromosome 21, what are the chances of recurrence based on which parent the defect came from?
The partial translocation has a higher chance of recurrence if it is from the father
What is the age related risk of trisomy 21 in a 22 year old mother?
1/1500
What is the age related risk of developing Down syndrome in a child born to a 40y/o mother?
1/90
Children with Down syndrome are at increased risk for what 4 conditions?
Leukemia
Duodenal atresia
Endocardial cushion defects
Atlantoaxial instability
What are the signs/symptoms of trisomy 13?
"BAD LUCK" Brain lesions (microcephaly / holoprosencrphaly) Abnormally low ears Digits (polydactyly) Leukocyte with nuclear projections Uterus bicornuate or hypoplastic ovaries Cleft lip/palate Kidneys (cystic)
What abnormalities exist in the extremities of a patient with Down syndrome?
5th digit dysplasia
Simian crease
Hyperextensible joints
Wide gap between 1st and 2nd toe
What syndrome would you consider in a patient with atrial septal defect and upper limb defects including three jointed thumbs?
Holt Oram syndrome
What syndrome should you consider in a child with self mutilation and choreiform movements?
Lesch nyhan syndrome
What lab abnormalities would you find in a child with lesch nyhan?
Elevated uric acid
A patient presents with rocker bottom feet and clenched fists, what syndrome should you consider?
Trisomy 18
What abnormal facial features would you find in trisomy 18?
Prominent occiput and low set ears
What organs might be found to be abnormal in a child with trisomy 18?
Horseshoe kidneys
What syndrome should you consider in a child with cafe au lait spots, fibrous dysplasia and precocious puberty?
Mccune Albright syndrome
What two syndromes show genetic imprinting and how?
Angelman - chromosome 15 (deletion from mom and 2 copies from dad)
Prader Willi - chromosome 15 (deletion from dad and 2 copies from mom)
What syndrome should you consider in a patient severe developmental delay, movement disorders and excessive laughing?
Angelman syndrome
What syndrome should you consider in a patient who is obese with small hands and testicles?
Prader Willi
What autosomal recessive disorder is characterized by progressive CNS, oohthalmologic and endocrine problems?
Laurence moon syndrome
What are the similarities and differences between Prader Willi and Laurence moon syndrome ?
Both have obesity and hypogonadism but only Laurence moon causes syndactyly and retinal dystrophy
What syndrome is associated with omphalocele, Macroglossia, hypospadias, hypoglycemia and hemihypertrophy?
Beckwith wiedemann
How do you test for digeorge syndrome?
Chromosomal analysis won’t detect the micro deletion - need FiSH study
If mother is a carrier if an X linked recessive disorder, what are the chances she will have an affected child?
25% will have disease
25% will be carriers
What are the chances that a mother who is a carrier of an x linked recessive disorder will have an affected male child?
50% will be affected
Can a female be affected by an X linked recessive disorder?
No! They can only be carriers!
What type of inheritance is androgen insensitivity?
X linked recessive
What type of inheritance is wiskott Aldrich?
X linked recessive
What type if inheritance is retinitis pigmentosa?
X linked recessive
What type of inheritance is nephrogenic diabetes insipidus?
X linked recessive
What type if inheritance is duchenne muscular dystrophy ?
X linked recessive
What type of inheritance is chronic granulomatous disease?
X linked recessive
What type of inheritance is hemophilia?
X linked recessive
What type of inheritance is G6PD deficiency ?
X linked recessive
What is the only x linked recessive disorder that can be found in a female?
Androgen insensitivity - patient is phenotypically female but is genetically XY
What are the 4 X linked dominant disorders?
X linked hypophospatemic rickets
Pseudohyperparathyroidism
Acardi syndrome
Alport syndrome
In what syndrome do patients present with macrocephaly, ocular abnormalities and absent corpus callosum?
Aicardi syndrome
What type of inheritance is peutz jeghers syndrome?
Autosomal dominant disorder
What type of inheritance is Von willebrand disease?
Autosomal dominant disorder
What type of inheritance is Huntington chorea?
Autosomal dominant disorder
What type of inheritance is waardenburg syndrome?
Autosomal dominant disorder
What type of inheritance is Gardner syndrome?
Autosomal dominant disorder
What type of inheritance is Marfan syndrome ?
Autosomal dominant disorder
What type of inheritance is neurofibromatosis?
Autosomal dominant disorder
What type of inheritance is retinoblastoma?
Autosomal dominant disorder
What type of inheritance is achondroplasia ?
Autosomal dominant disorder
What type of inheritance is tuberous sclerosis?
Autosomal dominant disorder
What type of inheritance are the porphyrias?
Autosomal dominant disorder
What type of inheritance is galactosemia?
Autosomal recessive
What type if inheritance is alpha 1 anti trypsin deficiency ?
Autosomal recessive
What type if inheritance is sickle cell disease and thalassemia?
Autosomal recessive
What type of inheritance are hurlers and Tay Sachs disease?
Autosomal recessive
What type of inheritance is ataxia telangiectasia?
Autosomal recessive
What type of inheritance is Wilson disease?
Autosomal recessive
What type of inheritance is PKU?
Autosomal recessive
What type of inheritance is kartagener syndrome ?
Autosomal recessive
When can chorionic villus sampling be performed?
12 weeks
When can amniocentesis be performed?
16 weeks
What is the best test in predicting fetal lung maturity? Why?
When is this test NOT accurate?
Phosphatidylglycerol - absent prior to 35 weeks gestation
Not reliable if diabetes - need total surfactant activity
What are the common findings in fetal alcohol syndrome ?
Short philtrum, thin upper lip, facial hypoplasia, short palpebral fissure and small 5th fingernail
What symptoms are associated with teratogenic exposure to anticonvulsants?
Microcephaly IUGR Cardiac defect Cleft lip Hypospadias Cryptorchidism Club foot Cardiac defect
What effects can lithium have on the developing fetus?
Ebsteins anomaly
What 5 things can occur to a fetus when mother is taking isotretinoin?
Microcephaly Micropthalmia Hypoplastic ears Truncus arteriosis Absent thymus
What specific defects are associated with carbamazepine during pregnancy ?
Spina bifida
Facial deformities
What specific defects are seen with phenytoin in pregnancy?
Finger stiffness Nail hypoplasia Cardiac anomalies skeletal anomalies Ophthalmology anomalies
What specific defects are associated with valproic acid during pregnancy?
Neural tube defects
What anatomical defects are associated with warfarin use during pregnancy?
Depressed nasal bridge
Hypoplastic distal phalanges
Stippled epiphyses
What fetal defects are found with ace inhibitor use during pregnancy?
Anuria
Oligohydramnios
Skull hypoplasia
Fetal hypotension
What is the charge association?
Coloboma & cognitive defects Heart disease Atresia choanal Retarded growth GU abnormalities Ear anomalies
What is associated with the VACTERL syndrome?
Vertebral defects Anal atresia Cardiac defects (VSD) TE fistula Renal defects Limb abnormalities
What is potter syndrome?
Oligohydramnios sequence = hypoplastic lungs, limb malformations (club feet, excess skin on hands), renal agenesis and IUGR
In what condition might the fetal membranes be covered in yellow nodules (amnion nodosum)?
Oligohydramnios (potter) sequence
In what syndrome do patients present with a broad thumb and cryptorchidism?
Rubinstein taybi syndrome
In what syndrome do patients present with broad thumbs and wide spaces eyes?
Pfeiffer syndrome
In what syndrome do patients present with a small chin and growth retardation?
Russell silver syndrome
What defects are associated with prune belly syndrome?
Bladder outlet obstruction
Oligohydramnios
Pulmonary hypoplasia
Undescended testes
What type or inheritance is treacher Collins?
Autosomal dominant
What syndrome is associated with conductive hearing loss, small jaw and low eyelid abnormalities?
Treacher Collins
What type of intelligence should you consider in a patient with small jaw and multiple family members with hearing aids ?
Treacher Collins - normal intelligence
What should you think of in a patient with intellectual disability with hx infantile spasms?
Tuberous sclerosis
What type of neurological abnormality might you expect in a patient with rhizomelic shortening and large heads?
Nerve root compression in small foremen magna in patient with achondroplasia
What syndrome would you suspect in a patient with elfin face, wide spaced teeth and upturned nose who is very friendly?
Williams syndrome
What lab or anatomical defect is associated with Williams syndrome?
Hypercalcemia
Supravalvular aortic stenosis
What is the most common inherited form of intellectual disability?
Fragile X
what is the chromosome abnormality in fragile X?
Repeat of CGG trinucleotide on X chromosome
What is the most common cause of genetic disability?
Down syndrome
What syndrome would you suspect in a male with large ears, macroorchidism and wierd behavior?
Fragile X syndrome
What syndrome presents with thick skull, corneal clouding and coarse facial features as well as intellectual disability ?
Hurler syndrome
What syndrome presents with thick skull, corneal clouding and coarse facial features as well as intellectual disability ?
Hurler syndrome
What are the similarities and differences between hurler’s and hunter’s syndrome?
Both have hepatosplenomegaly and progressive deafness
Hunters syndrome does NOT have corneal clouding and children are short
What are the similarities and differences between hurler’s and hunter’s syndrome?
Both have hepatosplenomegaly and progressive deafness
Hunters syndrome does NOT have corneal clouding and children are short
What type of inheritance is hunters syndrome?
X linked recessive
What type of inheritance is hunters syndrome?
X linked recessive
What testing is appropriate for diagnosing fragile X?
DNA testing is more sensitive than karyotype
What testing is appropriate for diagnosing fragile X?
DNA testing is more sensitive than karyotype
What would you consider in a patient with regression of developmental milestones and wringing hands?
Rett syndrome
What would you consider in a patient with regression of developmental milestones and wringing hands?
Rett syndrome
How do females with Rett syndrome regress?
Head growth decelerates at 4 months
Stagnation of development from 6-18 months
Loss of milestones between age 1-4 then no further decline
How do females with Rett syndrome regress?
Head growth decelerates at 4 months
Stagnation of development from 6-18 months
Loss of milestones between age 1-4 then no further decline
What syndrome presents with pointed nose, bird like face and small eyes?
Hallermann streiff syndrome
What syndrome presents with pointed nose, bird like face and small eyes?
Hallermann streiff syndrome
How is peutz jeghers syndrome inherited?
Autosomal dominant
How is peutz jeghers syndrome inherited?
Autosomal dominant
What syndrome should you suspect with mucosal pigmentation of lips and gums and hamartomatous polyps in intestines?
Peutz Jeghers syndrome
What syndrome should you suspect with mucosal pigmentation of lips and gums and hamartomatous polyps in intestines?
Peutz Jeghers syndrome
What is the appropriate treatment for peutz jeghers syndrome ?
Removal of polyps
What is the appropriate treatment for peutz jeghers syndrome ?
Removal of polyps
What syndrome should you consider in a patient with small chin, big tongue relative to chin, cleft palate and micrognathia?
Pierre Robin sequence
What syndrome should you consider in a patient with small chin, big tongue relative to chin, cleft palate and micrognathia?
Pierre Robin sequence
What extremity anomalies are common with Pierre Robin?
Syndactyly, clinidactyly, spinal deformities and hip anomalies
What extremity anomalies are common with Pierre Robin?
Syndactyly, clinidactyly, spinal deformities and hip anomalies
Does Pierre Robin sequence have developmental or neurological problems ? If so, what?
Language/motor delay
seizures
Does Pierre Robin sequence have developmental or neurological problems ? If so, what?
Language/motor delay
seizures
What cardiopulmonary abnormality may occur in Pierre Robin and why?
Cor pulmonale due to upper airway obstruction
What cardiopulmonary abnormality may occur in Pierre Robin and why?
Cor pulmonale due to upper airway obstruction
What is the first treatment for a patient with sturge weber? Why?
Ophthalmology referral to rule out glaucoma or urgent eye problems
What is the first treatment for a patient with sturge weber? Why?
Ophthalmology referral to rule out glaucoma or urgent eye problems
What syndrome should you suspect in a patient with port wine stain, developmental delay, seizure, hemipenis and vision problems?
Sturge weber
What syndrome should you suspect in a patient with port wine stain, developmental delay, seizure, hemipenis and vision problems?
Sturge weber
What should be done in a patient with ammonia between 200-600?
Benzoate and phenylacetate
What should be done if an infant had an ammonia level of >600?
Dialysis
What inborn errors of metabolism present with normal ABG and normal ammonia ?
Aminoacidopathy
Galactosemia
Non-Ketotic hyperglycemia
What inborn errors of metabolism are associated with normal ABG but elevated ammonia?
Urea cycle defect
Transient hyperammonemia
What inborn error of metabolism is associated with metabolic acidosis and high ammonia?
Propionic acidemia
Methylmalonic acidemia
Fatty acid oxidation defects
What inborn error of metabolism is associated with metabolic acidosis and normal ammonia?
Maple syrup urine disease
What is the normal serum ammonia value for a newborn?
<110
What might be the difference between an inborn error of metabolism and brain tumor in the history?
Brain tumor will have progressively worsening symptoms
What should be the first step after diagnosis of an organic acidemia?
Rehydration
What lab should be done in a 2 day old infant with acidosis, ketosis and high serum ammonia?
Urine organic acid levels
If you are presented with a patient who appears septic but is afebrile, what lab should be performed?
Serum ammonia , lactic acid, pyruvate, carnitine or acetylcarnitine
What should you consider in a patient with metabolic acidosis and bone marrow suppression?
Bone marrow suppression can occur with organic acidemias
What condition is associated with lethargy, poor feeding, seizures and odor of sweaty feet?
Isovaleric acidemia
What is the treatment of isovaleric acidemia?
Protein restriction
What treatment should be given for methylmalonic acidemia?
Vitamin B12
What is the inheritance pattern of fatty acid oxidation defects?
Autosomal recessive
How can you diagnose fatty acid oxidation defects?
Normal serum amino acids
NO reducing substances or ketones in urine
Plasma acylcarnitine profile
What condition would you consider in an infant with hypoglycemia and hepatomegaly after a benign illness?
Fatty acid oxidation defect
How are urea cycle defects treated?
Reducing protein intake and increasing glucose by IV
What do you do for a patient diagnosed with urea cycle defect who has ketonuria?
Think of a different diagnosis - possibly organic acidemias
What diagnosis should you consider in a patient hypotonia and dysmorphic features but normal ammonia?
Zellweger
What might be the diagnosis in a patient who was born normal but then developed abdominal distention, hypoglycemia and non-glucose reducing substances in the urine?
Galactosemia
What is the defect in patients with galactosemia? How do you diagnosis?
Deficiency of galactose 1 phosphate uridyltransferase (diagnose by measuring GALT in RBCs)
How do you treat galactosemia ? Why is it important to treat?
Galactose free diet - cataracts are reversible with diet change
Which symptom of galactosemia can be reversible with dietary changes?
Cataracts
What type of infections are common in children with galactosemia ?
Gram negative organisms such as E. coli
What is the treatment for children who have seizures after each meal? What disease is this?
Avoidance of fructose (disease is inherited fructose intolerance)
Infants of diabetic mothers are at high risk for what 4 endocrine conditions?
Hypoglycemia
Hyperbilirubinemia
Hypocalcemia
Polycythemia
What disease should you consider in a patient with hypoglycemia, acidosis, increased tone and seizures ?
Maple syrup urine disease
What condition presents with Macrosomia, microcephaly, Macroglossia and ohphalocele?
Beckwith wiedemann
What condition should you consider in a patient with hypoglycemia and ketonuria?
Adrenal insufficiency
Why do patients with beckwith wiedemann develop hypoglycemia?
Islet cell hyperplasia
What is the best medication for refractory hypoglycemia? (Resistant to insulin)
Diazoxide
What condition should you consider in a patient with lactic acidosis, rash, alopecia and neurological symptoms ?
Biotinidase deficiency
Which amino acids are elevated in patients with maple syrup urine disease?
Valine
Isoleucine
Alloisoleucin
Leucine
What test should you order in a patient with hypoglycemia, hepatomegaly and seizures?
Urine ketones and reducing substances
How is alcaptonuria treated?
Low phenylalanine and tyrosine diet
What disease causes “dark diaper” and why?
Alcaptonuria - homogentisic acid in the urine
Children with alcaptonuria may also have what conditions?
Arthritis and heart disease (but normal intelligence)
What condition presents with corneal ulcerations & plaques and thickened skin on the soles of the feet?
Oculocutaneous tyrosinemia
What amino acids are elevated in homocystinuria? And why?
Elevated methionine
What condition presents with dislocated lenses, skeletal abnormalities, light skin tone and cognitive defects?
Homocystinuria
What is the treatment for homocystinuria?
Pyridoxine OR diet of high cystine and low methionine
What is the difference between Marfan syndrome and homocystinuria ?
Marfan syndrome does NOT have cognitive defects but homocystinuria does
Marfan has anterior lens displacement but homocystinuria has posterior displacement
Patients with homocystinuria are at risk for what complications ?
Thrombi and emboli including PE
When should PKU screening be performed?
After first protein containing feeds
What disease should you consider in a patient who was normal at birth but at 3 months of age developed vomiting, eczema and mousy smelling urine?
PKU
Patients with PKU will develop what problems if they are left untreated?
Microcephaly
Low weight
Congenital heart disease
Profound intellectual disability
What is the treatment of PKU?
Low phenylalanine formula (lofenalac) and adequate tyrosine intake
What should a mother with PKU do prior to becoming pregnant? And why?
Low phenylalanine diet to prevent miscarriage, SGA, cardiac defects and intellectual disability
What lab findings may be present in children with hurler syndrome?
Reduced Alpha L iduronidase in WBCs
What syndrome presents with facial coarsening, hepatosplenomegaly and corneal clouding?
Hurlers syndrome
What is the transmittance of hurlers and hunters syndrome?
Hunters is X linked recessive
Hurlers is autosomal recessive
What lab findings are found in hunters syndrome ?
Low iduronate sulfatase enzyme activity
What disease presents with organomegaly, coarse facial features, joint contractures and pebbly skin?
Hunter syndrome
Which mucopolysaccharidosis presents with cognitive defects and minimal facial corsening?
Sanfilippo sundrome
What is an abnormal lab finding in sanfilippo syndrome ?
Urine with increased heparan sulfate
What condition presents with skeletal abnormalities, corneal clouding and normal intelligence?
Morquio syndrome
What condition presents with club feet, hip dislocation, joint contractures and severe intellectual disability ?
I-cell disease (mucolipidosis 2)
What are two purine and pyrimidine disorders?
Adenosine deaminase deficiency and lesch nyhan syndrome
What is the treatment for Von gierke disease?
Frequent meals and avoidance of fasting
Glucose infusion until age 2, then cornstarch is used
What is the underlying metabolic cause of Von gierke disease ?
Deficiency of hepatic glucose 6 phosphatase
What condition should you consider in a patient with doll-like face, hypoglycemia, hepatomegaly and high cholesterol?
Von gierke disease aka glycogen storage disease type 1
What lab findings are abnormal in Von Gierke disease?
Hypoglycemia with fasting
Elevated lactic acid and uric acid
What is the underlying metabolic cause of pompe disease?
Deficiency in lysosomal breakdown of glycogen
What disease should you consider in a one month old infant who suddenly becomes floppy with FTT, hypotonia, hard muscles, Macroglossia and hepatomegaly ?
Pompe disease aka glycogen storage disease type 2
What condition presents in a newborn after having his first protein containing feed who becomes lethargic and comatose ?
Non-Ketotic hyperglycinemia
Why is familial hypercholesterolemia associated with obesity?
It is not! It is due to deficiency of LDL receptors
What disease presents with an infant who is very thin and long die to fat tissue that is resistant to insulin?
Congenital lipodystrophy
What three conditions present with cherry red spot of the retina ?
Farber disease
Tay Sachs
Niemann pick
What disease presents with skin nodules and painful joints in the first week of life?
Farber disease
What disease presents with triglyceride and cholesterol esters deposited in the body tissues and calcified adrenal glands?
Wolman disease
What is the cause of menkes kinky hair syndrome ?
Low serum copper and low serum ceruloplasmin with high tissue copper
What disease presents with jaundice, hepatomegaly and neurological symptoms?
Wilson’s disease
What eye findings are common in Wilson’s disease ?
Kayser fleischer rings
But normal vision
How do you diagnose Wilson disease?
Liver biopsy
What disease presents with a child who was normal until age 2 when he developed hepatosplenomegaly, bone pain and easy bruising?
Gaucher disease
What X-ray findings may be seen in gaucher disease?
Osteosclerosis and lyric lesions
What is chronic juvenile gaucher disease?
Less severe form of gaucher with splenomegaly and thrombocytopenia but no CNS involvement
What disease presents with orange skin lesions, eye opacities and vascular disease of the kidney, heart and brain?
Fabry (a lysosomal lipid storage disease aka sphingolipidoses)
What is krabbe disease?
A sphingolipidoses with Demyelination with progressive degeneration resulting in death by age two
What is the underlying metabolic disorder that causes Tay Sachs disease?
Deficiency of hexosaminidase A
What disease presents with a normal child until age 9 months who develops lethargy, hypotonia, exaggerated startle reflex, macrocephaly and progressive neurological degeneration and death by age 5 ?
Tay Sachs
How can you screen for Tay Sachs disease?
Amniocentesis or CVS sampling
What is the difference between Tay Sachs and Niemann pick?
Both have cherry red spots but only Niemann pick has hepatosplenomegaly
What may cause a false positive PKU result on newborn screening? When should you suspect this?
Deficiency of teyrahydrobiopterin (bH4) - consider this if the patient remains symptomatic despite treatment for PKU
