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Flashcards in Syndrome Deck (19):

fragile X syndrome (FXS),

most common inherited and the second most common congenital cause of intellectual disability
- X-linked disorder caused by a loss-of-function mutation in the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome
-Males who inherit the full mutation will manifest the features of FXS, whereas females with one abnormal X chromosome will have a milder and variable presentation.
- clinical features of FXS are most apparent after puberty in males; affected individuals have a long, narrow face, a prominent forehead and chin, and large testes.
- Patients often have hyperlaxity of the joints in the hand.
- Developmental delay (speech and motor) is common in infancy, but neuropsychiatric features often present in childhood (eg, anxiety, attention deficit-hyperactivity disorder, autism spectrum disorder).


Down syndrome, or trisomy 21,

most common cause of congenital intellectual disability.
- Down syndrome mosaicism, some cells (but not all) have an extra copy of chromosome 21.
- milder presentation than those with classic Down syndrome.

- flat facial profile, upslanting palpebral fissures, low-set small ears, redundant skin at the nape of the neck, single transverse palmar crease, and hypotonia
- Increased rates of duodenal atresia and Hirschsprung disease are seen in these patients.


Ehlers-Danlos syndrome

- group of hereditary disorders involving a defect in collagen synthesis.
- manifests clinically as hypermobile joints, overelastic skin, and fragile tissue susceptible to bruising, wounds, and hemarthrosis
- Common mutations leading to EDS phenotypes include deficiencies of the lysyl hydroxylase and procollagen peptidase enzymes responsible for collagen synthesis.


Klinefelter syndrome (47,XXY)

mild intellectual disability in addition to tall stature, gynecomastia, small testes (often undescended), and infertility.


Marfan syndrome

autosomal dominant connective tissue disorder characterized by tall stature, arachnodactyly (long and thin fingers), ectopia lentis (lens displacement), and dilation of the proximal aorta.
- Intellectual disability is not associated

- fibrillin defect, causes cystic medial necrosis of the aorta and joint hyperextensibility

- It is not associated with a cleft palate, but rather with a high-arched palate with crowded teeth and a narrow face.


Prader-Willi syndrome

imprinting disorder caused by a paternal deletion of part of chromosome 15
- In infancy, hypotonia and hyperphagia lead to gross motor delays and obesity, respectively.


Patau syndrome, or trisomy 13

defect in the fusion of the prechordal mesoderm, an integral embryological structure affecting growth of the midface, eyes, and forebrain.
- results in catastrophic midline defects, including holoprosencephaly, microcephaly, microphthalmia, cleft lip/palate, and omphalocele.

Abnormal brain development results in intellectual disability and seizures.
- Additional abnormalities include polydactyly and cutis aplasia (focal skin defect of the scalp). The majority of patients with Patau syndrome die in utero; only 5% survive beyond 6 months.
Cytogenetic studies usually demonstrate meiotic nondisjunction, which is the failure of chromosomal separation during meiosis, causing inheritance of a chromosome pair from 1 parent rather than a single chromatid.

Maternal age >35 is an important risk factor for this abnormality of oocyte division. Nondisjunction results in a fetus with 3 complete copies of chromosome 13 (47, XX, +13).


Edwards syndrome (trisomy 18)

- fetal growth retardation, hypertonia, micrognathia, and congenital heart defects.
- Additional features include clenched hands with overlapping fingers, Meckel's diverticulum, and malrotation


Congenital rubella syndrome

- occurs after a first trimester maternal rubella infection.
- hearing loss, cataracts, and cardiac defects.


Williams syndrome

genetic disorder classically associated with "elfin" facies, supravalvular aortic stenosis, and an extroverted personality.


eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

- small to medium vessel vasculitis is characterized by late-onset asthma, rhinosinusitis, and eosinophilia, though it can involve many other organ systems including the kidneys, gastrointestinal tract, and cardiovascular system.

Asymmetric multifocal neuropathy (mononeuritis multiplex) is particularly common due to the vasculitis affecting the epineural vessels (eg, wrist drop due to radial nerve involvement).
- Other common manifestations include skin nodules, migratory/transient pulmonary infiltrates, and paranasal sinus abnormalities

- addition to peripheral eosinophilia, a frequent laboratory finding is antibodies against neutrophil myeloperoxidase, which most commonly have a pattern of perinuclear staining (p-ANCA).


Allergic bronchopulmonary aspergillosis (ABPA)

can produce an asthma-like picture with eosinophilia and elevated IgE and IgG serum antibodies to Aspergillus fumigatus


systemic sclerosis (scleroderma)

Pulmonary parenchymal involvement by systemic sclerosis (scleroderma) results in a chronic restrictive interstitial fibrosis.

Antitopoisomerase I (Scl-70), anticentromere, and anti-RNA polymerase III antibodies are highly specific for systemic sclerosis.


DiGeorge syndrome and velocardiofacial syndrome

Chromosome 22q11.2 microdeletion involves deletion of genes residing in adjacent loci.

- results in variable phenotypes including DiGeorge syndrome (cardiac anomalies, hypoplastic/absent thymus, hypocalcemia) and velocardiofacial syndrome (cleft palate, cardiac anomalies, dysmorphic facies)

- Defective neural crest migration into derivatives of the third and fourth pharyngeal pouches results in maldevelopment of the thymus and parathyroid as well as subsequent T-cell deficiency and hypocalcemia.

- Cardiac defects include interrupted aortic arch and tetralogy of Fallot

- Dysmorphic facial features include orbital hypertelorism, short palpebral fissures and short philtrum, cleft palate, and bifid uvula

fluorescence in situ hybridization (the gold standard test), genes of interest are hybridized with fluorescently labeled DNA probe. Lack of fluorescent signal is indicative of a microdeletion.


Kartagener syndrome

- results from immotile cilia due to an autosomal recessive microtubular defect in the dynein arm.

- results in infertility, situs inversus, chronic sinusitis, and bronchiectasis.


Prader-Willi syndrome (PWS

Microdeletion syndrome due to genomic imprinting

- paternal genes are deleted (15q-) and maternal genes are silenced, resulting in short stature, obesity, hypotonia, and hypogonadism.


Angelman syndrome (AS)

maternal genes are deleted (15q-) and paternal genes are silenced.

- Patients have microcephaly, ataxia, hand flapping movements, and frequent laughter ("happy puppet").


Tuberous sclerosis

defective tumor suppressor gene-coded proteins hamartin (TSC1) and tuberin (TSC2), and is characterized by cutaneous angiofibromas, brain hamartomas, and cardiac rhabdomyomas.


Friedrich ataxia (GAA repeat) i

spinocerebellar degeneration and spinal ataxia.