Syndromes/Eponymous Flashcards
McCune Albright Syndrome
Polyostotic disease + precious puberty + cutaneous pigmentation
Features: Polyostotic fibrous tissue, scoliosis, cafe-au-lait spots, precocious puberty, endocrine issues (hyperthyroidism, excess growth hormone, hypercortisolism and Cushingoid, GI polyps
Cause: GNAS mutation -> abnormal G protein receptor -> constitutive activation, adenylate cyclase “on”
Polyostotic fibrous dysplasia is a form of fibrous dysplasia affecting more than one bone. Fibrous dysplasia is a disorder where bone is replaced by fibrous tissue, leading to weak bones, uneven growth, and deformity.
Kabuki Syndrome
Features: Distinctive facies (arched eyebrows, long eyelashes, elongated eyelids with lower lids that turn out, prominent ears, a flat tip of the nose and a downward slant to the mouth), growth delay, intellectual disability, skeletal abnormalities, short stature
Cause: Mutation in methyltransferase or demethylase
Other: 2nd most common syndromic form of hyperinsulinaemia hypoglycaemia (1st is Beckwith Weidemann)
Beckwith Wiedemann Syndrome
Features: Overgrowth disorder - macrosomia, macroglossia, organomegaly, exomphalos
May have asymmetric growth / hemihyperplasia
Increased risk of tumours
Most common syndromic cause of hyperinsulinaemia hypoglycaemia (due to pancreatic hypertrophy)
i. Overgrowth disorder, predisposition to tumour development
ii. Maternally imprinting disorder 11p15.5 region in ~1/2
iii. Genes that code IGF2, H19 (tumour suppressor gene), CDKN1C and others
iv. H19 is maternally expressed, IGF2 paternally expressed
v. ~20% caused by uniparental disomy
vi. Tumour risk = Wilms and hepatoblastoma most common, also neuroblastoma, adrenocortical carcinoma and rhabdomyosarcoma + others
1. ~7.5% risk, range 4-21%
vii. Most before 8 years of life
An exomphalos (also known as omphalocele) is the herniation of abdominal organs through a central abdominal wall defect. It is different from a gastroschisis in that it has a membrane that covers the abdominal contents and is more likely to have associated major congenital anomalies or be part of a syndrome.
Autoimmune polyendocrinopathy (polyglandular) syndrome 1
Features: Widespread autoimmunity
Cause: AIRE gene -> abnormal thymus antigen expression or negative selection -> widespread autoimmunity
- Chronic mucocutaneous candidosis
- Hypoparathyroidism
- Adrenocortical insufficiency
While the symptoms of APS-1 are variable in each patient, they often will have components of at least two of the three major conditions that result from this syndrome: chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency.
Wolfram Syndrome (DIDMOD)
Features: Diabetes insipidus, diabetes mellitus, optic atrophy, deafness
Cause: Mutation in WFS1 gene
Other: Definition/diagnosis requires T1DM + optic atrophy
IPEX Syndrome
Features: Immune dysfunction, polyendocrinopathy, enteropathy
Inheritance: X-linked
Cause: Mutation in FOXP3 -> decreased Treg cells -> overwhelming autoimmune disease
Right Middle Lobe Syndrome
Features: Recurrent or chronic obstruction or infection of right middle lobe of lung
Other: Classified as intrinsic/extrinsic, obstructive/non-obstructive
E.g. lymphadenopathy
ROHHAD
Features: Rapid onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation
Other: 40% have neural crest derived tumours e.g. neuroblastoma
Ramsy Hunt Syndrome
Features: Facial paralysis with painful vesicles in the auditory canal or auricle
Cause: Reactivation of herpes zoster virus in the 7th cranial nerve (shingles CNVII)
AKA herpes zoster oticus
Kawasaki Disease Shock Syndrome
Features: Kawasaki disease presenting with cardiogenic shock
Apert Syndrome
Features: Congenital skeletal abnormalities of skull/face/hands/feet (craniosynostosis, fused/webbed fingers/toes), intellectual disability
Inheritance: de novo / sporadic
Craniosynostosis is characteristic
Currarino Triad
Features: Anorectal malformations (ectopic, stenosis, imperforate), sacral bone anomalies (hypoplasia, poor segmentation), presacral anomaly (anterior meningocele, teratoma, cyst)
Yellow Nail Syndrome
Features: Pleural effusion, lymphoedema, discolouraed nails
Cause: unknown
Marnier Kuhn Syndrome
Features: Congenital tracheobronchomegaly -> congenital bronchiectasis
Williams Campbell Syndrome
Features: Congenital absence of annular bronchial cartilage -> congenital cystic bronchiectasis
Shah Waardenburg Syndrome (Waardenburg syndrome type 4)
Features: Neurocristopathy -> Hirsprungs, deafness, depigmentation
Inheritance: AR
Ondine’s Curse
Features: Congenital central hypoventilation, symptoms occur during sleep and are fatal if untreated
A/W: Neuroblastoma, Hirschprungs, dysphagia
Treatment: Respiratory support, ventilation, tracheostomy
Icteropyloric Syndrome
Features: Hypertrophic pyloric stenosis + hyperbilirubinaemia
Zellweger Syndrome
Features: Hypotonia, poor feeding, impaired hearing and vision, skeletal anomalies, +/- involvement of liver, heart, kidneys
Most severe form of Zellweger spectrum (leukodystrophies - Leukodystrophy refers to a group of genetic conditions that affect the white matter of the brain)
Cause: Dysfunctional peroxisomes, due to PEX1 mutation
Inheritance: AR
Joubert Syndrome
• AR disorder – ciliopathy
• Genetic heterogeneity
Key triad: cerebellar/brainstem malformation, hypotonia, developmental delay
• Clinical manifestations o Hypotonia, ataxia (toddler) o Breathing abnormalities – episodic apnoea and hyperpnoea o Global developmental delay o Strabismus o Occulomotor ataxia
Treatment: Supportive
Goldberg-Shprintzen Syndrome
Features: Megacolon, microcephaly, intellectual disability, characteristic facies
A/W Hirschprungs
Gene: KIAA1279
Inheritance: AR
Horner Syndrome
Features: Unilateral ptosis, miosis, anhidrosis
A/W thoracic/cervical primary tumour
Symptoms do not resolve with tumour resection
Hutchinson Syndrome
Features: Limping and irritability, due to skeletal mets from neuroblastoma
Pepper Syndrome
Features: Extensive liver mets from primary adrenal neuroblastoma, with or without respiratory distress
I.E. stage 4S/MS neuroblastoma
Opsoclonus Myoclonus Ataxia Syndrome
Features: Neuroblastoma a/w myoclonic jerking and random conjugate eye movements, +/- cerebellar ataxia
Likely immune mediated
Often progresses to neuropsychologic sequelae
Kerner Morrison Syndrome
Features: Neuroblastoma a/w intractable secretary diarrhoea d/t tumour secretion of vasointestinal peptides
Neurocristopathy Syndrome
Features: Neuroblastoma a/w other neural crest disorders, e.g. congenital hypoventilation syndrome, Hirschprungs
Gene: PHOX2B
Eisenmenger Syndrome
Progression of untreated congenital cardiac defect with intracardiac communication:
L-R shunt -> increased pulmonary blood flow -> increased pulmonary vascular resistance -> inverted shunt to R-L -> cyanosis
Cornelia de Lange Syndrome
Features: Developmental disorder, affecting facies, growth, intellectual disability, limb defects
Gene: NIPBL
Inheritance: AD, XL, de novo
Smith Lemli Opitz Syndrome
DHCR7 mutations
Deficiency in enzyme 7-dehydrocholesterol reductase -> abnormal cholesterol metabolism
Inheritance: AR
• Craniofacial malformations • Developmental delay • Growth failure • Cholesterol deficiency Under virilised male (46XY DSD)
Koebner Phenomenon
Cutaneous hypersensitivity with classic lesions brought on by superficial trauma
Feature of sJIA
Macrophage Activation Syndrome
Rare but potentially fatal complication of systemic juvenile idiopathic arthritis, can occur at any time
Features: high fevers, lymphadenopathy, hepatosplenomegaly, encephalopathy
Thrombocytopenia, leukopenia, elevated ferritin (can be really high e.g. >10,000), low ESR
Treat with IV methylpred
Lemierre’s syndrome
= Jugular Vein Suppurative Thrombophlebitis
• Typically anaerobic gram –ve rod – Fusobacterium necrophorum oral flora
• Begins as pharyngitis or tonsillitis -> thrombophlebitis -> seeding of multiple organs with septic emboli particularly lungs
• Acute fever, hypoxia, tachypnea, WOB
• CXR – multiple cavities
• Pneumonia may lead to respiratory failure in untreated cases
• Anaerobic BC, USS of jugular veins
CT of chest -> Dx
Lemierre’s syndrome is a condition characterized by thrombophlebitis (inflammation d/t blood clot) of the internal jugular vein and bacteremia caused by primarily anaerobic organisms (fusobacterium necrophorum most commonly), following a recent oropharyngeal infection. This has been an uncommon illness in the era of antibiotic therapy, though it has been reported with increasing frequency in the past 15 years. Lemierre’s syndrome should be suspected in young healthy patients with prolonged symptoms of pharyngitis followed by symptoms of septicemia or pneumonia, or an atypical lateral neck pain. Metastatic infections following the IJ thrombophlebitis occur in >2/3 of cases (lungs, joints, liver, muscle, pericardium, brain and skin). Diagnosis is often confirmed by identification of thrombophlebitis of the internal jugular vein and growth of anaerobic bacteria on blood culture. Treatment involves prolonged antibiotic therapy occasionally combined with anticoagulation.
Alice in Wonderland Syndrome
Alice in Wonderland syndrome (AIWS) is a rare neurological disorder characterized by distortions of visual perception, the body image, and the experience of time. People may see things smaller than they are, feel their body alter in size or experience any of the syndrome’s numerous other symptoms. Since there are also many known causes of AIWS, diagnosis requires a thorough neurological work-up. In children, the most common cause is brain inflammation; in adults, it is migraine.
Brugada Syndrome
Brugada Syndrome is an ECG abnormality with a high incidence of sudden death in patients with structurally normal hearts. Brugada syndrome is due to a mutation in the cardiac sodium channel gene. A/W early cardiac death. Only proven therapy is an implantable cardioverter-defibrillator (ICD).
Diagnostic criteria: Brugada sign on ECG (Coved ST segment elevation >2mm in >1 of V1-V3 followed by a negative T wave) plus at least one clinical criteria of: Documented ventricular fibrillation (VF) or polymorphic ventricular tachycardia (VT), Family history of sudden cardiac death at <45 years old, Coved-type ECGs in family members, Inducibility of VT with programmed electrical stimulation, Syncope, Nocturnal agonal respiration.
Wolf Parkinson White Syndrome
Wolff-Parkinson-White (WPW) Syndrome is a combination of the presence of a congenital accessory pathway and episodes of tachyarrhythmia. Pre-excitation refers to early activation of the ventricles due to impulses bypassing the AV node via an accessory pathway. In WPW the accessory pathway is often referred to as the Bundle of Kent, or atrioventricular bypass tract.
ECG features of WPW in sinus rhythm are:
PR interval <120ms
Delta wave – slurring slow rise of initial portion of the QRS
QRS prolongation >110ms
ST Segment and T wave discordant changes – i.e. in the opposite direction to the major component of the QRS complex
Pseudo-infarction pattern can be seen in up to 70% of patients – due to negatively deflected delta waves in the inferior / anterior leads (“pseudo-Q waves”), or as a prominent R wave in V1-3 (mimicking posterior infarction).
POTS (Postural Orthostatic Tachycardia Syndrome)
Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by too little blood returning to the heart when moving from a lying down to a standing up position (orthostatic intolerance). Orthostatic Intolerance causes lightheadedness or fainting that can be eased by lying back down. In people with POTS, these symptoms are also accompanied by a rapid increase in heart rate.
Jaccourd arthropathy
Late sequelae of acute rheumatic fever.
Jaccoud arthropathy is a benign, chronic arthropathy that involves loosening and lengthening of periarticular structures and tendons in the hands and/or feet. The deformities are painless, “correctable” with manipulation, and do not cause functional impairment. The arthropathy is not associated with active joint inflammation.
Sandifer syndrome
Sandifer syndrome is a condition that involves spasmodic torsional dystonia with arching of the back and rigid opisthotonic posturing, associated with symptomatic gastroesophageal reflux, esophagitis, or hiatal hernia.
Herring-Breuer reflex
Excessive inflation (stretch receptors) triggers this reflex which is protective to further inflation as it inhibits inspiratory neurons
Mounier-Kuhn syndrome
Congenital tracheomegaly
A lung disorder that causes the respiratory tract to dilate or enlarge. People with this condition develop frequent respiratory tract infections and recurrent cough.
Wilson Mikity Syndrome
Wilson Mikity syndrome (WMS) refers to chronic lung disease in premature infants, characterized by early development of cystic interstitial emphysema (PIE). This is now sometimes considered as part of the spectrum of bronchopulmonary dysplasia.
Kartagner triad
1) situs inversus totalis
2) chronic sinusitis
3) bronchiectasis
(Primary ciliary dyskinesia)
Airway assessment scores/classifications
Modified Mallampati scoring of airways
Class 1 – fully visible tonsils, uvula, soft palate
Class 2 – visibility of hard and soft palate, upper portion of tonsil and uvula
Class 3 - soft and hard palate and base of uvula visible
Class 4 – only hard palate
Significant correlation between Mallampati score + AHI on sleep study
For every point increase in Mallampati score odds ratio of OSA increase more than 6 fold
Tonsil size - Brodsky’s classification of tonsillar size
Grade 0 – tonsil in tonsillar fossa
Grad 1 - tonsil 25% oropharynx
Grade 2 – 25-50%
Grade 3 – 50-75%
Grade 4 - >75%
For every point increase in tonsillar size, the odds ratio of having OSA increase >2 fold
Cataplexy
Sudden and temporary loss of muscle tone
Pathognomonic for narcolepsy if present
Rarely the first symptom of narcolepsy
Usually brief (seconds to minutes) but in children may last for hours or days (‘status cataplecticus’)
Scimitar Syndrome
Also known as hypogenetic lung syndrome, is characterized by a hypoplastic lung that is drained by an anomalous pulmonary vein into the systemic venous system. It is a type of partial anomalous pulmonary venous return and is one of the several findings in congenital pulmonary venolobar syndrome.
CXR: a crescent shaped vertical shadow in the right lower lung
Noonan syndrome
Noonan syndrome is a common genetic disorder with multiple congenital abnormalities. It is characterized by congenital heart disease (hypertrophic cardiomyopathy, pulmonary stenosis with dysplastic valve), short stature, a broad and webbed neck, sternal deformity, variable degree of developmental delay, cryptorchidism, increased bleeding tendency, and characteristic facial features that evolve with age.
Dysplastic valves are frequently seen.
