Syndromes Flashcards
NF-1
The diagnostic criteria are (2 of the following are required):
Six or more café-au-lait spots or hyperpigmented macules >5mm in diameter in pre-pubertal children and 15mm post-pubertal
Axillary or inguinal freckles (>2 freckles)
Two or more typical neurofibromas or one plexiform neurofibroma
Optic nerve glioma
Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist
Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis
First-degree relative (e.g. mother, father, sister, brother) with NF1
Cardiac- coartation of aorta
Wilson’s disease
In Wilson disease, there is decreased incorporation of copper into apoceruloplasmin and decreased transport of copper from the liver into bile, leading to copper excess in tissue despite low circulating levels of ceruloplasmin (the major form of circulating copper).
reducing the major pathway of hepatic copper elimination that is responsible for the clinical manifestations and pathology of Wilson disease.
Lesch Nyhan
X linked disorder of purine metabolism
Developmental retardation
hypotonia
chorea /dystonia/hyperreflexia/spasticity
Self mutilating behavior usually self biting
XXY
Klinefelter syndrome is the most common congenital abnormality causing primary hypogonadism, occurring in approximately 1 in 1000 live male births. It is the clinical manifestation of a male who has an extra X chromosome.
The most common genotype is 47,XXY (which is shown above).
47,XXY genotype results from nondisjunction of the sex chromosomes of either parent during meiotic division, while mosaicism probably results from nondisjunction during mitotic division after conception.
The greater the number of extra X chromosomes, the greater the phenotypic consequences, both gonadal and extragonadal.
Phenotypic changes would include:
Damage to the seminiferous tubules and, usually, damage to the Leydig cells as well: almost invariably small, firm testes; severely subnormal sperm count; infertility; elevated serum FSH and LH concentrations; variably subnormal serum testosterone concentration and; decreased virilisation
Long bone abnormality, resulting in increased length of the legs, independent of the increased length of both the arms and legs caused by testosterone deficiency.
Behavioural abnormality, unrelated to the hypogonadism, which causes difficulty in social interactions throughout life.
Predisposition to develop morbidities later in life that are unrelated to testosterone deficiency: pulmonary diseases such as chronic bronchitis, bronchiectasis, and emphysema; cancers, including germ cell tumours (particularly extragonadal tumours involving the mediastinum), breast cancer, and possibly non-Hodgkin lymphoma; varicose veins, leading to leg ulcers; diabetes mellitus.
Aicardi syndrome
absence corpus collosum
chorioretinal lacunae –> blindness
seizures
developmental disability
Walker Warburg Syndrome
most severe of congenital muscular dystrophy
hypotonia
coloboma, cataracts
“cobblestone” lissencephaly
fatal within first few years of life
Goldenhar syndrome
AD
- Triad: 1) mandibular hypoplasia resulting in hemifacial asymmetry, 2) ocular (limbal dermoid, eyelid coloboma) and auricular malformations (MICROTIA, preauricular skin tag) and 3) vertebral anomalies (missing vertebare, scoliosis)
- Unilateral facial hypoplasia, mandibular hypoplasia
- Hemivertebre/fused/butterfly vertebrae
- Cleft palate
-Condunctive hearing loss
-Congenital cardiac disease
DDX- Treacher collins syndrome (similar but BILATERAL)
CHARGE
coloboma
heart defects
atresiae choanae
retarted growth and development
genitourinary defects
ear abnormalities
Achondroplasia
Stenosis of spinal canal - spinal cord compression at foramen magnum
- hypotonia, central and obstructive sleep apnoea, sudden death. may need surgical correction
Lumbar stenosis can present in adulthood as parastheia, numbness, claudicaiton in legs
Cleidocranial dysplasia/dysostosis
delayed closure of the cranial sutures, dental abnormalities and hypoplastic clavicles.
Klippel-Feil syndrome
The classic triad of a short neck (C2-3 fusion) low hairline and limited range of movement of the neck occurs in less than 50%.
Duane syndrome
Congenital strabsmus
Abnormal development of 6th cranial nerve (abducens) –> anomalous inneervation of lateral rectus
There are three types and there is a helpful mnemonic to remember this: children with type 1 have difficulty with abduction (one D in abduction), type 2 have difficulty with adduction (two Ds in adduction) and type 3 have difficulty with both (3 Ds in abduction and adduction). Approximately 80% of cases are type 1.
Associated with Klippel Feil and hemifacial macrosmia
L>R eye
Freidereich ataxia
autosomal recessive disorder involving the spinocerebellar tracts, dorsal columns in the spinal cord, the pyramidal tracts, and the cerebellum and medulla. The onset of ataxia is somewhat later than in ataxia-telangiectasia but usually occurs before age 10 years. The ataxia is slowly progressive and involves the lower extremities to a greater degree than the upper extremities. Patients develop a characteristic explosive, dysarthric speech, and nystagmus is present in most children. Typically noted is a marked loss of vibration and position sense caused by degeneration of the posterior columns and indistinct sensory changes in the distal extremities. Absent lower limb reflexes. Friedreich ataxia is also characterised by skeletal abnormalities, including high-arched feet (pes cavus) and hammertoes, as well as progressive kyphoscoliosis.
hyprtrophic cardiomyopathy
Treacher collins syndrome
AD
- External ear abnormalities (bilateral microtia)- conductive hearing loss in 50%
- Eye abnormalities- down slanting eyes, coloboma of lower eyelids
- Hypoplasia of mandible
- Cleft palate
- Obstructive sleep apnoea
- Dental problems
Albright hereditary osteodystrophy (pseudohypoparathyroidism
· Short stature
· Short metacarpals and metatarsals
· Round facies
· Delayed dentition, +/– hypocalcemia and/or subcutaneous calcium or bone deposition (osteoma cutis)
· Precocious puberty
· Mild cognitive deficit
Bardet-Biedl
· Obesity
- Mental retardation
· Hypotonia
· Retinitis pigmentosa/ rod cone dystrophy
· Post axial Polydactyly
· male hypogonadotropic hypogonadism
· +/– glucose intolerance
· Deafness
· Renal disease
22q11 microdeletion
Defective development of 3rd and 4th pharyngeal pouches
Look for lack of thymus on CXR and prolonged QT (hypocalcemia) on ECG
May have SCID phenotype
X linked hypophosphatemia
X linked dominant (both males and females are affected equally)
Most common form of hereditary hypophosphatemic rickets
Loss of function PHEX gene
Renal phosphate wasting
–> hypophosphatemia, slow growth, rickets/osteomalacia
Patau syndrome
T13
haloprosencephaly
scalpdefect
cleft lip/palate
midline anomalies
90% die by 1 year
Edwards syndrome
T18
IUGR
wizened features
rockerbottom feet
90% die by 1 year
why need to do a karyotype for T21 diagnosis
for preconception councelling next pregnancy
4% T21 due to translocation (seen on karyotype but not microarray)
if maternal 14,21 translocation: recurrence risk 10-15%
T21 complications
hypothyroidism 15%
atlanto axial instability
deafness 75%
visual problems 60%
osa 75%
AML
Turners syndrome features
short stature
cardiac- bicuspid aortic valve, CoA
primary ovarian failure (gonadal dysgenesis= streak ovaries)
lymphoedema
HTN
renal anomalies- 50%
increased risk hypothyroidism and celiac
risk aortic dissection
Kleinfelter
47 XXY
hypergonadotropic hypogonadism
raised LH, FSH–> but low testosterone
Almost all infertile
Increased risk germ cell tumors and breast cancer
increased risk metabolic syndrome, hypothyroid, vte, osteoporosis
Ix: karyotype, microarray
22q11
cardiac- conotruncal : TOF 35% , interupted aortic arch 20% , truncus 10%
abnormal facies
thymic hypoplasia
cleft palate
hypocalcemia- check ecg for long QT
hearing loss
failure development 3 +4th branchial arches
Ix: microarray
Psychiatric illness in 60%, autism in 20%
Williams syndrome
Microdeletion 7q
dysmorphic
overly friendly cocktail personality
hypercalcemia
supravalvar aortic (and pulmunary) stenosis
risk GA- MI
