Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

a_Genetics > 11/17- Genetic Disorders You Don’t Want To Miss Part II: The Pediatric Patient > Flashcards

11/17- Genetic Disorders You Don’t Want To Miss Part II: The Pediatric Patient Flashcards

1
Q

Case 1)

  • 2 month old male presents to the ER with swelling of his left arm
  • He refuses to move the arm and cries with palpation
  • Parents report no history of trauma
  • Child protection team meets and they feel that this injury is consistent with child abuse but request genetics consultation to rule out disorders that can mimic child abuse
  • What next?
A

Genetic consult

  • Further history reveals that mother occasionally pulls the infant to sitting position by his hands
  • Family history: Mother is 32 years old and is healthy. Father is 30 years old and has a history of 12 fractures in his lifetime, several of which occurred with minimal trauma. Father’s ethnic background is German/Irish. Mother’s ethnic background is Mexican.
  • No history of other family members with multiple fractures.
  • There is no known consanguinity.

Suspect Osteogenesis Imperfecta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Key physical exam findings of Osteogenesis Imperfecta?

A
  • Grayish tint to sclera
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which OI type is the classic?

A

OI type I: classic non-deforming OI with blue/grey sclera

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the other OI types/main phenotypes?

A
  • OI type I: classic non-deforming OI with blue/grey sclera

- OI type II: perinatally lethal OI

- OI type III: progressively deforming OI

- OI type IV: common variable OI with normal sclerae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe OI type I

  • Protein involved
  • Symptoms
  • Associations
A
  • Type I collagen
  • QUANTITATIVE defect in Type I Collagen
  • Multiple recurrent fractures
  • Normal stature
  • Little or no bone deformity
  • Blue sclera
  • Hearing loss in 50%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are genetic testing recommendations for OI?

A

COL1A1 and COL1A2 genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Case 2)

  • 7 mo old girl
  • Presents to PCP for routine well-child care (a month late)
  • Normal newborn screen.
  • No hospitalizations or surgeries
  • Mild developmental delay (she is not yet sitting independently)
  • Physical examination
  • Alert and playful.
  • Macrocephaly. (FOC was normal at birth, it has been steadily increasing over time.) Soft anterior fontanelle.
  • Mild generalized hypotonia, normal reflexes and normal CNs.
  • What is seen in the CT
  • What test would evaluate macrocephaly?
  • What do you suspect?
A
  • CT of brain shows large bilateral subdural hematomas
  • Glutaric aciduria type 1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is seen here?

A

MRI imaging with opercular cisterns (bat sign)

  • Increased signal in globus pallidus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What should a non-accidental trauma investigation involve?

A
  • Retinal exam (look for hemorrhages/shaken baby)
  • Skeletal survey (fractures)
  • MRI imaging
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What metabolic results do you expect to see in Glutaric Aciduria Type I?

A

Urine Organic Acids

  • ↑glutaric acid
  • ↑ 3OH-glutaric acid

Plasma Acylcarnitines

  • ↓ plasma carnitine
  • ↑ glutaryl carnitine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the pathogenesis Glutaric Aciduria Type I (don’t memorize)

A
  • Deficiency in glutaryl-CoA dehydrogenase in mitochondria which mediates the decarboxylation of glutaryl-CoA to crotonyl-CoA in the degradation pathway of lysine, hydroxylysine and tryptophan.
  • Accumulation of glutaric acids can result in acute striatal necrosis resulting in metabolic stroke.
  • Resulting damage to the globus pallidus can result in resting tremor, rigidity, dyskinesia, and hypotonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What factors can lead to what serious complication in Glutaric Aciduria type I?

A

Stress, concurrent illnesses, and surgery can precipitate metabolic stroke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is treatment for Glutaric Aciduria type I?

A
  • Low-protein diet
  • Supplemental carnitine
  • Medical management: emphasizing importance of emergent medical attention and caloric support in times of illness, decreased caloric intake, stress, and surgery.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the genetic component of Glutaric Aciduria type I?

  • What testing should be done
A

This is an autosomal recessive disorder with RR of 25% for parents

  • Prenatal testing via DNA analysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe Glutaric Aciduria Type I

  • Genetic inheritance
  • Prevalence - More in what populations
  • Testing when
  • Presentation when
  • Prognosis
A

- Autosomal recessive

  • 1/30,000
  • 1/300 Amish and Ojibway-Cree
  • On NBS panel, but may be negative
  • Typically presents 6-18 months
  • Macrocephaly; poor feeding; irritable; mild hypotonia; dystonia; dyskenesia
  • Mild manifestations may be overlooked
  • Prognosis variable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Case 3)

  • 4 year old male presents to his PCP with parental concerns about “spots” that have appeared over the past year
  • PMH: Previously healthy, no hospitalizations or surgeries. Full term, NSVD.
  • Development: Patient is showing some delay in learning his colors, but his motor development has been normal
  • PE: relative macrocephaly (95th %ile), multiple hyperpigmented macules scattered over chest, back, and extremities (>10 in total). Freckling in the axilla and inguinal regions
  • Diagnosis?
A

Neurofibromatosis Type I

17
Q

What are the clinical criteria for NF type I?

A
  • Café au lait macules (6+)
  • Neurofibromas or one plexiform neurofibroma (2+)
  • Frecking in the axillary or inguinal regions
  • Optic glioma
  • Lisch nodules (2+)
  • Sphenoid dysplasia or tibial pseudoarthrosis
  • Affected first degree relative
18
Q

What is seen here? Seen in what condition?

A

Lisch nodules

  • Benign iris hamartomas
  • Seen in NF type I
19
Q

What is seen here? Seen in what condition?

A

Tibial psueodarthrosis

  • One of the bone abnormalities you may see in NF type I
20
Q

What is seen here? Seen in what condition?

A

Optic pathway glioma

  • NF type I
21
Q

What is seen here? Seen in what condition?

A

Neurofibromas

  • NF type I
22
Q

What is seen here? Seen in what condition?

A

Plexiform Neurofibromas

  • NF type I
23
Q

How is NF type I diagnosed? Caveats?

A

Based on clinical criteria

  • Early in course patient may not meet the clinical criteria soGenetic Testing (NF1 gene sequencing) can be done to rule in the diagnosis.
24
Q

Describe genetics of NF type I

  • Gene involved
  • Inheritance pattern
  • Penetrance
  • Expressivity
  • Recurrence risk
A
  • Heterozygous loss-of-function mutations of NF1
  • Pathogenic variants are very heterogeneous
  • Autosomal dominant
  • Typically penetrant
  • Extremely variable expressivity even within family
  • Recurrence risk: 50%
25
Q

What is management/treatment for NF type I?

A

Management involves close follow up and therapy for various organ system involvement.

  • Routine examinations should focus on the potential complications.
  • Annual examinations permit early detection of problems, decreasing morbidity and improving quality of life.
  • Annual eye examinations are important in early detection of optic nerve lesions. mTOR (rapamycin complex 1) inhibitors shown to slow tumor growth
  • Others in investigation.
26
Q

Case 4)

  • 14yo male presents to dermatology clinic for evaluation for acne refractory to OTC meds.
  • PMH: Seizures controlled on Keppra, ADHD on Ritalin.
  • PE: Ash leaf spot, Shagreen patch, Perinungual fibroma
  • What are you thinking for Dx?
A

Tuberous sclerosis

27
Q

What are physical exam findings of tuberous sclerosis?

A
  • Ash leaf spot
  • Shagreen patch
  • Periungual fibroma
28
Q

What are major features of Tuberous Sclerosis?

A
  • Facial angiofibromas
  • Hypomelanotic macules (three or more)
  • Shagreen patch (connective tissue nevus)
  • Cortical tuber
  • Subependymal nodule (SEN)
  • Cardiac rhabdomyoma, single or multiple
  • Lymphangiomyomatosis
  • Renal angiomyolipoma
29
Q

Describe the genetics of Tuberous Sclerosis

  • Genes
  • Inheritance pattern
  • Penetrance
  • Expressivity
  • Mutation rate
A
  • Caused by mutation in one of two genes:
  • TSC1 and TSC2
  • Autosomal dominant inheritance
  • Complete penetrance
  • Variable expressivity
  • High new-mutation rate (~70% de novo mutations)
30
Q

What is management/treatment for Tuberous Sclerosis?

A

Multidisciplinary followup and management of various organ system involvement.

31
Q

Case 5)

  • 24 yo female who presents with auditory hallucinations and paranoid delusions
  • She is diagnosed with schizophrenia
  • PMH: History of ADHD and learning disability in childhood
  • History of heart murmur as a child that resolved without intervention
  • What genetic test should be ordered?
A

Test for 22a11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial syndrome)

32
Q

What are clinical features of 22q11.2 (DiGeorge/Velocardiofacial syndrome)?

A

CATCH 22 (chrom 22)

  • Cardiac abnormality
  • Abnormal facies
  • Thymic hypoplasia/aplasia
  • Cleft palate
  • Hypocalcemia / Hypoparathyroidism
  • Other features: learning difficulties in 70-90%
33
Q

Describe the timing and clinical features of DiGeorge

A
  • Very mild to very severe
  • Varies based on age (prenatal, neonatal, infancy, childhood, adolescent, adult)
34
Q

What are features of intrauterine fetal devo at 24 wks with DiGeorge?

A

Intrauterine fetal disease (complication of DiGeorge that may be missed)

  • Absent thymus
  • Conotruncal heart defect
  • Absent parathyroid glands
35
Q

How to diagnose del(22q11.2)?

  • When is it diagnosed
  • Incidence
A

1/2-4,000

Timing:

  • Birth (3050
  • By 5 yrs (70%)
  • By 18 yrs (95%)

Sx: psychotic symptoms are seen in 14-28% of children

Dx: aCGH

36
Q

Describe the DiGeorge presentation for each age group:

  • Neonatal
  • Infancy
  • Early childhood
  • Late childhood
  • Adolescence
  • Adulthood
A
  • Neonatal: major CHD, Hypocalcemic seizures, Immunodeficiency
  • Infancy: feeding difficulty
  • Early Childhood: developmental delay
  • Later Childhood: learning disabilities
  • Adolescence: behavioural psychiatric problems
  • Adulthood: parent who has a child with deletion 22q11.2 syndrome
37
Q

What is the recurrence risk for DiGeorge?

A

50% for those with deletion

a_Genetics (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions