Smattering of 15 Random Disorders Flashcards
What gene is affected in Smith Lemli Opitz?
DHCR7
The DHCR7 gene provides instructions for making an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the production of cholesterol.
Name 9 facial features of Smith Lemi Opitz
- Broad nasal tip with anteverted nose
- Micrognathia
- Ptosis of eyelids
- Epicanthal folds
- Broad maxillary alveolar ridges
- Low set ears
- Syndactly (fusion) of 2nd and 3rd toes
- Post-axial polydactly
- Cleft palate
Name 2 eye features of Smith-Lemli Optiz
- Strabismus
2. Cataracts
Name 3 GU features that can be seen with Smith Lemi Opitz
- Hypospadias
- Cryptorchidism
- Ambiguous genitalia
Name 3 other features seen in Smith Lemi Opitz
- Abnormal cholesterol synthesis
- Heart murmurs
- Intellectual disability
Name the features of VACTERL
V- vertebral anamolies A- anorectal malformations C- cardiac (VSD, TOF, ASD, PDA) T- tracheal E- esophageal fistulas/ abnormalities R- Renal L- limb (radius)
How is VACTERL inherited?
Sporadic
What are the features of CHARGE syndrome?
C- coloboma, cranial nerves
H- heart disease (VSD, ASD, PDA, TOF, endocardial cushion defect)
A- atresia choanae
R- Retarded growth/development and or CNS anomolies
G- genital anomalies or hypogonadism
E- ear anomalies or deafness
Need 4/6 dx
What is the most common genetic mutation that causes CHARGE syndrome?
Mutation in the chromodomain helicase DNA (CHD7 gene) binding protein gene on chromosome 8q12.2 in 60%
Name 7 features of Cornelia de Lange syndrome
- Low birthweight
- Cleft palata
- Thick eyebrows that typically meet in the midline (synophrys)
- Long eyelashes
- Limb differences (missing limbs or portions of limbs)
- Excessive body hair
- Long philtrum
- Small widely spaced teeth
- Partial joining of the 2nd and third toes
- Incurved 5th finger
Name 4 neurologic features of Cornelia de Lange
- Seizures
- Developmental Delay
- Microcephaly
- Hearing/vision impairment
What causes Pallister-Killan syndrome?
Mosaicism for an isochromosome 12p (ie chromosome 12 contains two identical p arms without a q arm)
Name 5 physical features of Pallister-Killan syndrome
- Coarse facies
- Abnormal ear lobes
- Localized alopecia
- Pigmentary skin anomalies
- Supernumerary nipples
Name 2 cardio/resp complications of Pallister-Killan syndrome
- Diaphragmatic hernia
2. Cardiovascular abnormalities
Name 2 neurologic complications of Pallister-Killan syndrome
- Seizures
2. Profound intellectual disability
What causes Cri du Chat?
Deletion of 5p, usually de novo
Name 5 neuro features of Cri Du Chat
- Microcephaly
- Protruding metopic suture
- Shrill cry in the first few weeks of life (cat-like)
- Hypotonia
- Cognitive disability
Name 5 physical features of Cri Du Chat
- Hypertelorism
- Bilateral epicanthal folds
- High arched palata
- Wide/flat nasal bridge
- Short stature
What causes Sotos Syndrome
NSD1 mutations in 90% cases this gene makes a histone methyltransferase protein
How is Sotos Syndrome inherited?
Autosomal dominant
What is unique about growth in Sotos syndrome?
Excessive physical growth in first 2-3yrs, then normal after
What is Sotos syndrome associated with increased risk of?
Cancer; though not one specific type of cancer has been identified.
What are 6 physical features of Sotos Syndrome?
- Disproportionately large and long head, with a slightly protruding forehead
- Small pointed chin
- Flushed cheeks
- Large hands and feet
- Hypertelorism
- Downslanting eyes
Name 4 developmental or behavioural issues seen with Sotos Syndrome
Any of:
- Mild intellectual disability
- Delayed motor/cognitive/social development
- Speech impairment
- ADHD
- Phobias
- OCD
- Tantrums
Name 4 neurological features seen in Sotos Syndrome
- Hypotonia
- Prominence of extra-axial fluid spaces on MRI
- Poor coordination
- Seizures
What causes Sturge Weber syndrome?
Mutation on chromosome 9q21
What skin feature is seen in Sturge Weber?
Port wine stain usually in the distribution of the trigeminal nerve (present at birth, do not proliferate)
What 4 neurologic features are classic for Sturge Weber syndrome?
- Leptomeningeal angiomatosis (+blood vessel growth)
- Hemiparesis contralateral to the facial lesion
- Seizures
- Intellectual disability
Name 3 eye features associated with Sturge Weber syndrome
- Glaucoma
- Enlarging eye
- Optic atrophy
What does PHACES syndrome stand for?
P- Posterior fossa and other brain malformations (esp Dandy-Walker malformation of cerebellum)
H- Large hemangiomas of the face/neck/scalp
A- Anatomical abnormalities of the cerebral or cervical (A)rteries
C- Cardiac anomalies (coarctation most common)
E- Eye abnormalities
S- Sternum abnormalities
What causes Klinefelter Syndrome?
Most common sex chromosome aneuploidy.
- 80% are 47, XXY
- Can have multiple sex chromosome aneuploidies (48 XXXY, 48XXYY, 49 XXXXY)
Note: greater the aneuploidy= more severe mental impairment/dysmorphism
Are individuals with Klinefelter phenotypically male or female?
Male.
Name 8 features of individuals with Klinefelter syndrome (not including cognitive features)
- Hypogonadism/infertility
- Puberty at a normal age
- Small testes
- Late secondary sexual characteristics
- 50% gynecomastia
- Tall stature
- Long legs
- inc risk Cryptorchidism
Name 3 cognitive features of individuals with Klinefelter Syndrome
- Variable intelligence
- Behavioural problems/LD
- Language deficits and impaired social skills
What causes Kabuki syndrome?
Mutation in KMT2D
Name 7 facial features seen in Kabuki syndrome
- Long palpebral fissures
- Eversion of the lateral lower eyelid
- Large protuberant ears
- Cleft palate
- Tooth abnormalities
- Blue sclerae
- Tethered nasal tip
Name 3 neurologic features of Kabuki syndrome
- Hypotonia
- Feeding problems
- Mild-moderate ID
How is Ehlers Danlos Syndrome inherited?
Most are AD
What are the different types of Ehlers Danlos syndrome
Classic (I and II) Hypermobility (III) Vascular (IV) Kyphoscoliosis (VI) Dermatospataxis (VII) Arthrochalasis (VIII)
What are the major criteria for Ehlers Danlos?
- Skin hyperextensibility
- Wide atrophic scars
- Joint hypermobility
Name 9 Minor criteria for Ehlers Danlos Syndrome
- Smooth velvety white skin
- Underlying vessels visible
- Doughy feel to skin
- Molluscoid pseudotumours are small spongy tumours found over scars and pressure points.
- Subcutaneous spheroids
- Mucous membrane hypoplasia
- Easy bruising
- MV prolapse
- Aortic root dilation
What causes Russel Silver syndrome?
2 causes identified so far
- 30-60% dt loss of methylation, hypomethylation of 11p15 imprinted region
- Maternal uniparental disomy for chromosome 7
Name 3 growth/skeletal features of Russel-Silver Syndrome
- Small stature
- Late closure of the anterior fontanelle
- Short or curved 5th finger (clinodactyly)
Name 5 facial/physical features of Russel Silver Syndrome
- Small triangular face
- Frontal bone prominence
- Downturned mouth
- Bluish sclera
- Excessive sweating
True or false: Cafe au lait spots can be seen with Russel Silver syndrome
True
Name 3 disorders that present with cafe au lait spots
- NF1
- Russel Silver Syndrome
- Fanconi’s Anemia
Name 1 important endocrine feature of Russel Silver syndrome
- Fasting hypoglycemia from 10mo to 2-3yo
Name 3 features of Pierre Robin Sequence
Think of the most nightmarish child ever to intubate:
- Micro/retrognathia
- Cleft palate
- Glossoptosis (downward displacement and retraction of the tongue)
How is Waardenburg syndrome inherited?
AD
Pigmentary disorder with abnormal melanocyte distribution
Name 4 features of Waardenburg syndrome
- Patchy depigmentation of the skin/hair
- Heterchromic iridis
- Broad nasal root
- Congenital deafness
