epeat exceeds a threshold length, no fragile X protein is made, and disease results. Signs: \200\201Flexibility in adapting to the changing demands that life brings ( \200\201 atten tional set-shifting), 90 big testes, big jaw, high forehead, \200\201IQ (not always); 91 p oor learning, facial asymmetry, long ears, short temper. Also: hyperactivity, emotional and behavioral problems, anxiety, mood swings, autism, tactile defensiveness (little eye conta ct; no hugging; hype rsensitive to touch & sound, ?from slowed mid-trimester maturation of the sensory cortex). Tests: Prenatal tests are possible. Screening could be general or of h igh-risk groups (eg families with >1 retarded \200 ). Screening for carrier status leads t o labeling and stigmatization, and is rejected by some families. 92 s e m o r d n y s s u o m y n o p e l a u s u n U 649 Fig 1. Lewy body (arrow). NB: there are no generally accepted biomarkers to distin- guish d ementia with Lewy bodies (DLB) from other dementias. Think of DLB when- ever there is progr essive anxiety, depres- sion, apathy, agitation, sleep disorder with psychosis and memory d isorders. The best imaging candidate may be striatal dopamine transporter system scintigrap hy using FP-CIT SPECT.93 EEG is helpful \200\224but dif- \201 cult and the application of criteria needs an expert.94 s e m o r d n y s s u o m y n o p e l a u s u n U Courtesy of Kondi Wong / NLM. Li \200\223Fraumeni syndrome, p53, and the guardian of the genome p53 is a tumor-suppressor gene (chromosome 17p13.1; encoding nuclear phos- phoprotein, a transcription factor allowi ng passage through the cell cycle). In this syndrome, as only one allele is aff ected, deve lopment is normal until a spontaneous mutation aff ects the other allele. Somatic mutation of p53 oc- curs at both alleles in 50 \200\22380% of spontaneous human cancers. Cells with a p53 mutation do not pause in G1 (a phase in which DNA repair takes place, and faulty DNA purged), but proceed straight to S1 (DNA replication), which is why p53 protein is known as the \200\230guardian of the genome \200\231. Examples of cancers caused this way: early-o nset breast cancer; brain tumors; sarcomas; leukemia; lym- phoma; melanoma; adrenal cortex carcinoma. 95 Note that tumors are associated with more than one syndrome, eg adrenal cortex tumors are a ssociated with familial cancer syndromes such as the Beckwith \200\223Wiedemann and Li \200 \223Fraumeni syndromes, the Carney complex (p699), multiple endocrine neoplasia type 1, con genital adrenal hyperplasia, and the McCune \200\223Albright syndrome (p650). 96 In a retrospective study of 200 cancer-aff ected carriers of TP53 germline mutations, 15% d eveloped a 2nd cancer, 4% a 3rd cancer, and 2% a 4th cancer. 97 In some populations (eg in South Brazil) there is a high prevalence of otherwise rare mutations in p53, partly explain ing high rates of colon and other cancers (eg fatal stomach cancers in children as young as 12). 98 McCune \200\223Albright syndrome Polyosteotic \201 brous dysplasia of bone, irregular are as of skin pigmentation and facial asymmetry precocious puberty. Monteggia fracture # of the proximal \205\223 of ulna, with angulation + radial head subluxation, caused forced p ronation. Open reduction/plating aids good align- ment (5wks in plaster). Wait for full uni on ( 12wks) before normal arm use.99 Morquio \200\231s syndrome (mucopolysaccharidosis IV A utosomal re c e s s i ve) Lysosomal storage disease caused by \200\201N-acetylgalactosamin e-6-sulfate sulfatase. Signs: Stature \200\201; deaf; weakness; broad mouth; widely-spaced teeth; aortic regurgitation.100 IQ \200\211. Moyamoya disease Vascular disease at the circl e of Willis causes strokes/TIAs (alternating hemiplegia, dyspraxia, \201 ts, involuntary movements, headache).101 Typical patient: Japanese girl, with triggering infection (eg tons illitis) or hy- perventilation (CO2 \200\201 causes vasoconstriction). Digital subtraction angiogra- phy: Collateral vessel formation \200\230like a puff of smoke \200\231. MRI/CT: Multiple infarc- tions in watershed areas. \201\227: Bypass surgery may be possible.101 Ni emann \200\223Pick disease Autosomal re c e s s i ve A neurovisceral lysosomal lipid storag e disor- der.102 After years of normal growth, there is physical and mental decline, psy- c hosis, wasting, and hepatosplenomegaly from abnormal metabolism of sphin- gomyelin. Other s igns: brown skin patches; a cherry red spot on the macula; AST \200\200. \201 : Sphingomye linase activity in peripheral blood white cells.103 Noonan syndrome Hypertrophic cardiomyop athy, VSD/ASDs, bruising (APTT \200\200; \200\201factors VIII, XI, XII), ptosis, down-slan ting eyes, low-set ears, webbed neck. Height, IQ, social functioning & hearing are \200 \201,104 but not severely. 50% have germ-line PTPN11 mutations ( associated neuroblastom aet al).105 ECG: Left axis deviation45%, small R wave in V624%; abnormal Q wave6%. 106 Prev alence: 1:5000. Ondine \200\231s curse Failure of migration neural crest cells \200\203auto nomic dysfunction \200\203central alveolar hypoventilation \200\203apnoea during sleep.107 Ondine was a nymph who sacri \201 ced her immortality by falling in love with a prince wh o promised to honor her with every waking breath. As she began to age, the prince lost inte rest. Ondine was furious, uttering her curse: \200\234for as long as you are awake, you sh all breathe. But should you ever fall asleep, that breath will desert you \200\235. Othello syndrome (morbid jealousy) A lover believes, against all reason, that his beloved is being sexually unfaithful, thinking that she is plotting against him, or deliberately making him impotent. He may engage a spy, and obses- sively examine her underwear for signs of sexual activity. Associations: alco- hol, schizophrenia, depression, right frontal lobe problems. 108 \200\207Get psychiatric help: jealousy is the most deadly of all the passions, and ou tlasts all others. 109 \200\234Without my having seen Albertine \200 there would \202 as h from my memory some vision of her with Gis le in an attitude which had seemed innocent t o me at the time; it was enough now to destroy the peace of mind I had managed to recover, I had no longer any need to go and breath dangerous germs outside, I had, as Cottard [p640] would have said, supplied my own toxin. \200\235Marcel Proust: ch2 of Patau \200\231s synd rome (trisomy 13) Cleft lip & palate, microcephaly, ompha- locele, hernias, patent ductus a rteriosus, VSD dextrocardia, capillary hae- mangiomata, and polycystic kidneys. Hands sh ow \202 exion contractures polydactyly/narrow \201 ngernails. Antenatal management: See BOX 3. Typical survival: A few days; 5% survive >6 months. Prevalence: 1 in 7500 births . 110 Pick \200\231s dementia Prevalence: 15:100,000 aged 45 \200\22364yrs. Signs: Before c ogni- tive loss, look for: 111 character change, frontal lobe signs, eg tactless disinhibi- tion stealing, practical jokes, callousness, sexual (mis)adventures, fatuous euphoria/d epression, odd eating habits/impaired satiety, 112 jargon dysphasia. Delusions (rare).113 T ests: MRI. \201\227: Drugs, eg memantine et al, often fail. 114 See BOX. Pierre Robin synd rome Poor neonatal feeding & breathing due to microg- nathia (short chin) cleft palate o r eye abnormality. Prevent the tongue slipping back by nursing on the belly (chest elevated on pillow) or by surgery.115 650 s e m o r d n y s s u o m y n o p e l a u s u n U Sodome & Gomorre 651 Distinguishing Pick \200\231s dementia from Alzheimer \200\231s disease (AD) Histology: Ins tead of the neuro \201 brillary tangles of AD, look for severe atro- phy, neuronal loss, g liosis, ballooned neurons (Pick cells), and argentophilic neuronal inclusions (Pick bodies) especially in frontal and temporal cortical regions. (Pick \200\231s is a type of frontote mporal dementia and all types tend to show disinhibition, character change, increased appet ite, sexual misconduct and language problems.)116 Epidemiology: Pick \200\231s runs a short er course, starting earlier than AD. \200 : \200 >1:1 A good history from carers is quite good at distinguishing the conditions. Sensitivity: 79%. Speci \201 city: 90%.117 See OPP OSITE for discriminating signs. NB: memory and visuospatial dysfunction may less aff ected than in AD. On examination: Re \202 exes such as grasp, suck, and snout; plastic rigidity. s e m o r d n y s s u o m y n o p e l a u s u n U Fig 1. Meckel \200\231s diverticulum Prevalence: \211 2%. \211 2 inches long, and >2 feet from the ile- ocaecal valve (antemesenteric aspect of il- eum); it contains gastric and pa ncreatic tis- sue. \201 : Radioisotope scan; laparotomy may be the cause of occult GI pain and bleeding (brick red stools, or dark becoming bright). It is a leading cause of rectal bleeding ( GI obstruction) in children. Dr Thomas Tracy. Hyper-endocrinopathies, McCune \200\223Albright syndrome, and the Taiwanese giant In the Mc Cune \200\223Albright syndrome, precocious puberty is not the only endo- crinopathy: hypert hyroidism and Cushing \200\231s also occur. In the case of the \200\230Tai- wanese giant \200\231 (an unfortunate name) excess growth hormone production has also been found.118 Def ormities, fractures, and pain further complicate the picture (sometimes ameliorated by IV p amidronate). The craniofacial \201 brous dysplasia may encroach on the optic nerve, causi ng visual problems. GNRH analogs have been used (experimentally) to treat the precocious pu berty.119 The cause may be a mutation of the GNAS 1 gene coding the \200 subunit of the s timulatory guanine-nucleotide binding protein, G-protein, which activates adenylate cyclase ( \200\230 \200\200intracellular cyclic AMP).120 Ethical considerations severe trisomy conditions If the patient \200\231s views are known , comply with them. This excellent principle only gets us so far in obstetrics, where there are 2 potential patients whose needs may be in con \202 ict eg during antenatal diagnosis of a uniformly lethal condition (L+) or a uniformly severe commonly lethal condition (L , eg tri- somy 13 or 18). What do doctors actually do with these uncomfortably nested bombs ? Not every doctor will discuss termination even for L+ conditions, but most do. If the mot her decides to continue her pregnancy and is requesting obstetric non-intervention, 99% of us comply with her views for both L+ and L conditions. 121 Most of us try to be encouragi ng for such management, but some of us are non-directive or discourage this management. In continuing pregnancies where the mother changes her mind and wants a late termina- tion, mo st of us are willing to comply for both L+ (71%) and L (82%) conditions. What do we make of these discrepancies? Patients may be off ered diff erent options based on doctors \200 \231 ethical or religious backgrounds. If the doctor does not comply with patient wishes he or she may be wise to get a second opinion, and should be prepared to be challenged throug h the Courts, where opposing ethics are decided one way or another, for better or worse, by judges who may never have heard of trisomy \200\224that, of course, is their great strengt h: their superb ignorance immunizes them against bias. Captain Pollard syndrome A state of mind (known to all doctors) caused by de stroying the v ery person we had hoped to protect due to over-indulging views of colleagues. In 1821 he fo und himself eating his 17-yr-old cousin (whom he had promised to protect) while adrift with out food on the Paci \201 c after a series of giving way to the other \200\231s views on h ow to conduct his fatal whaling expedition. Pompe \200\231s glycogen storage disease (GSD-I I) \200\201Lysosomal \200 1,4-glucosidase activity leads to progressive weakness and fail ure to thrive. 2 forms: infan- tile and late-onset. 122 IQ \200\201 & sepsis occur. Glycoge n accumulates in heart (do echo); muscle; liver; CNS; kidney; adrenals. \201\227: Alglucos idase alfa prolongs life and can reverse cardiomyopathy. Gene therapy might be curative in future. 123 Prader \200\223Willi syndrome (PWS) Cause: Loss of paternal contribution of the proximal part of the long arm of chromosome 15. Prevalence: 1:25,000. \201\231 : See BOX. Signs: Blue eyes and blond hair hypersomnolence,124 hyperphagia/pica (eg for dog biscui ts, or shop-lifting food). Toddlers may be passive, autistic, or introverted or develop uns table moods. Those who are extrovert may develop psychosis. Tests: Chromosome analysis. EEG : slow spike & wave activity.125 Ramsay Hunt syndrome (herpes zoster oticus) Severe otalgia , often in the el- derly, precedes VII & other cranial nerve palsies. Zoster vesicles appea r around the ear, in the deep meatus ( soft palate & tonsillar fossa). There may be verti go sensorineural deafness.126 \201\227: Valaciclovir 1g/8h PO127 + prednisolone (p574). 128 Rett disorder X-linked. Development: Normal at \201 rst. Diagnosis (according to DSM IV-TR): A: All of the following: \200 Normal prenatal and perinatal devel- opment \200 Normal psychomotor development for 5 months after birth \200 Nor- mal head circumference at birth. B: Onset of all of the following after a pe- riod of normal development: \200 \200\201Head growth between 5 and 48 months old \200 Loss of previously acquired purpose ful hand skills between 5 and 30 months (development of stereotyped movements, eg hand wrin ging or hand wash- ing) \200 \200\201Interest in social activities early in the course \200 Ataxic gait or trunk movements \200 Impaired expressive & receptive language + psyc homotor retar- dation. \201 : Sequencing of MECP2 gene mutations (the cause in 70%).129,13 0 Reye \200\231s syndrome Encephalopathy occurs days after a febrile viral illness (vari- c ella, in \202 uenza). Aspirin intake is a risk factor131 (and maybe antiemetics/anti- hist amines). Median age:uk 14 months. Tests: Transaminases \200\200; glucose \200\201; blood am monium \200\200 (correlate with survival); INR \200\200. Liver biopsy: swollen, pleomorphic mitochondria (ATP \200\201, gluconeogenesis & ureagenesis \200\201). CNS MRI: cerebral oed e- ma; white matter changes.132 \201\231 \201\231: Inherited metabolic disorders (IMD). Se e BOX. Russell Silver syndrome A heterogeneous congenital disorder, character- ized by seve re intrauterine and post-natal growth retardation, dysmorphic facial features, asymmetrical growth, small stature and precocious puberty. The cause usually unknown. Association: Wilm s \200\231. Aberrant genomic imprint- ing (eg involving chromosome 11p15.5) may be to blame .133 In imprinting, DNA sequences have conditional behavior depending on if they are matern ally or paternally inherited. The idea is that there is some imprint put on the DNA in the mother \200\231s ovary or in the father \200\231s testes which marks that DNA as being ma- ternal or paternal, and in \202 uences expression in their progeny. 134,135 Shakhonovich \200\231s syndrome (hypokalaemic periodic paralysis) Attacks (1 \200\22324h) of \202 acci d paralysis, spreading up from the legs triggered by: stress, menses, cold, carbohydrate lo ads, rest after exercise, or liquorice. Speech, eye movements & swallowing are OK. Age: 7 \200\22321yrs. Signs: During attacks, mus- cles feel \201 rmer than usual. Re \202 exes: diminished. Genes: Mis-sense mutations of CACNA1S (type 1) & SCN4A genes (type 2) aff ecti ng the voltage sensor of the transmembrane segment of Ca2+ channels (type 1) and Na+ channe ls (type 2).136 Tests during attacks: \200 K+ \200\201; PO4 3 \200\223 \200\201; urate \200\200; WCC \200\200; glycosuria. 137 \201\227: IVI/oral K+ can help; acetazolamide prev ents some attacks, depending on genetic diagno- sis. Genetic counseling. 138 \201\231 \201 \231: Hypokalaemic thyrotoxic periodic paralysis. 139 652 s e m o r d n y s s u o m y n o p e l a u s u n U 653 Diagnosing Prader \200\223Willi if <3yrs old Likely if > 5 points if 3 from Major criteria (1 point each) \200 Feeding problems failure to thrive \200 Hypogonadism \200 Deve lopmental delay \200\201IQ \200 Rapid weight gain (1 \200\2236yrs of age; NB: wt norm al in 26%, if aged 6 \200\22317)140 Minor criteria ( \201 point each) \200 \200\201Feta l movement/infantile lethargy \200 Short stature small hands and feet \200 Esotropia /myopia \200 Speech articulation defects Prader \200\223Willi syndrome (PWS) and epigenet ic proof of existentialism Chromosome 15q11 \200\223q13 is a critical region for PWS and An gelman syndrome (AS, a totally diff erent syndrome of frequent laughter, ataxia & hypotonia giv- ing a puppet-like gait \200\224happy puppet syndrome).141 PWS results from loss of ex pression of paternally expressed genes and AS of maternally expressed genes from the same l ocus. How do the genes know where they come from? They bear an imprint of their origin. Thi s is genetic imprinting \200\224an example of epigenetics \200\224ie transgenerationally-tr ansmissible functional changes in the genome that can be altered by environmental events an d don \200\231t involve an alteration of DNA sequences. What we expose our genes to today m ay be in \202 uencing the lives our grandchildren can lead. Mouse models show that this ca n be inherited down unlimited generations. major criteria s e m o r d n y s s u o m y n o p e l a u s u n U Central hypotonia \200 Characteristic facial features Sleep disturbance sleep apnoea \200 Hypopigmentation \200 Thick viscous saliva \200 Skin picking In humans we know that permanent reactions to stress (eg increased glu- cocorticoid recepto r sensitivity, eg after a terrorist outrage) can be inherited down at least one generation. 142 Another example of the environment control- ling genomic events is the association of B eckwith \200\223Wiedemann syndrome (p638) with embryos that have been stored and treated in unusual ways during IVF. Furthermore, changes in our diet may activate certain pathways le aving an imprint that is passed to the next generation (Kaati \200\231s hypothesis is suppo rted by data on harvest yields in Overkalix in northern Sweden: a pro- pensity to diabetes is inherited only if there is a surfeit of food during the time leading up to one \200\231s grandfather \200\231s puberty).143,144 A cardinal precept of genetics has always been that we cannot choose what we pass on to the next generation. But epigenetics opens up an unlimited dialog between genes and our enviro nment. It is likely that we can be re- sponsible by free choice whether a gene is turned on or off (eg by exposing ourselves to pesticides or smoke) \200\224and this turning-off may be inherited in an unchanging way. \200\207We need to nurture our own genome carefully for fu- ture generations. Does this mean that we have a duty to be happy and lead a stress-fre e life? We don \200\231t know. What we do know is that the existentialists have a point \200\224it is as if we are all now responsible for everything forever. And this knowledge m ay itself be stressful. By confronting this stress and making free choices we can authentic ate our dialog with our genes. Staging and treatment of Reye \200\231s syndrome Stage 2 (or worse) should prompt rapid referral to a tertiary center able to monitor ICP and intra-art erial pressure. Stage 2 criteria: inappropriate ver- balizing, combative or stuporose, purp oseful or non-purposeful response to pain, sluggish pupillary responses, intact eye re \202 ex. Management: \200\207Correct hypoglycaemia with a continuous IVI of 10 \200\22315% glucose. Restrict \202 uids; do blood glucose every 2h; give vitamin K 0.25mg/kg slowly IV (monitor pro- thrombin time); lower ICP (p200). Aim for 40mmHg cerebral perfusion pres- sure (=systolic BP minus ICP). Control T and seizures. Mortality: <20%, from brainstem dy sfunction. Since abandoning aspirin in children, incidence has fallen to \200\2051 \200 \2236 patients/yr/106 children <16yrs.145 Still \200\231s disease (systemic-onset juvenile idiopathic arthritis/JIA) presents with sy stemic upset eg in a prepubertal girl with synovitis, cartilage erosion fever, pericardi tis, iridocyclitis, pneumonitis (lung biopsy speci \201 c), lymphade- nopathy, splenomegal y. It is a cause of walking on tip-toes ( \201\231 \201\231: short Achilles tendon; habit; muscle contractures; cerebral palsy). 146 88% get arthritis (8% mono-, 45% oligo-, 47% poly articular) \200\224eg of knee (68% of patients with ar- thritis), wrist (68%), and ankle (5 7%). 147 Latex is \200\223ve. 148 Other subgroups: juve- nile ankylosing spondylitis; psor iatic arthritis; ulcerative colitis-associated ar- thritis; juvenile-onset rheumatoid arthr itis: here Rh factor is +ve, and systemic upset is rarer (eg DIC, liver/renal failure; amyl oid; cardiac tamponade; sterile endocarditis; peritonitis; macrophage activation/cytokine s torm). 149 654 s e m o r d n y s Adult-onset Still \200\231s disease (AOSD) diagnostic criteria \200\224all of: daily fever >39 C; arthralgia/arthritis; Rh factor and antinuclear factor \200\223ve plus any 2 of: W CC >15 \211\210 109/L; rash; serositis (pleural/pericardial); hepatosplenomegaly; ad- enop athy \200\224provided that SBE, leukemia & sarcoid are excluded. Tests: WCC \200\200; ESR \200\200; CRP \200\200 ( \211\210poor response); Hb \200\201; ferritin \200\200; LFT \200 \200; albumin \200\201; echo. 150 \201\227: \200\207The chief challenge for the child is to negotiate between their protected status as a \200\230sick child \200\231, their own re sponsibility in illness management, and the need to achieve a normal lifestyle. 151 Try mil d exercise; then rest for 1h each day. If hips are aff ected, physio to prevent contracture s by encouraging extension (eg lying prone on the \202 oor to watch TV). Splinting, tract ion, and non-weight-bearing exercises help. Hot baths help morning stiff ness. Consider toc ilizumab (may halt radiographic progression by blocking interleukin-6 re- ceptors; SE dysli pidaemia), methotrexate (may help uveitis too), penicillamine, gold, and hydroxychloroquine . 152 Intra-articular triamcinolone may be tried.153 Synovectomy154 may conserve joint func tion. 155 Sydenham \200\231s chorea (St Vitus dance) This is still the chief cause of chore a in children, and is a major manifestation of acute rheumatic fever (p166). It may be the only feature, appearing up to 6 months after clinical and lab signs of strep infection have abated. This may start with emotional lability and a preference for being alone ( attent ion span \200\201). Other non-motor features: in- clude obsessions, compulsions, attention de \201 cit, \200\201verbal \202 uency, \200\201executive function. 156 Motor signs: p urposeless movement, worsened by stress and dis- appearing on sleep, with clumsiness, grima cing, a darting lizard \200\231s tongue and unclear speech. The term PANDAS (pediatric auto immune neuropsychiatric disorder associated with streptococcus) denotes a putative subset o f obses- sive \200\223compulsive disorder and Tourette \200\231s syndrome (OHCM p714) that bears some resemblance to Sydenham \200\231s chorea.157 \201\231 \201\231: Wilson \200\231 s disease, juvenile Huntington \200\231s, thyrotoxicosis, SLE, polycythaemia, Na+ \200\201, hypoparathyroidism, kernicterus, encephalitis lethargica, subdural haematoma, alcohol, phe nytoin, neuroleptics, hereditary chorea, neuroacanthosis. \201\227: Often self-limiting, b ut treat if chorea interferes with life. Sodium valproate (15 \200\22320mg/kg/day) or carba mazepine can control chorea within 1 week. 158 Despite treating active and recurrent strep infections vigorously, chorea may persist. 156 Syme \200\231s amputation An amputation imme diately proximal to the ankle. re c e s s i ve Type I gangliosidosis aff ecting 1:4000 Ash kenazi Tay \200\223Sachs disease Autosomal Jewish births. It is a disease of gray matter. T here is \200\201lysosomal hexosamini- dase A. Low levels of enzyme are detectable in carri ers. Children are normal until 6 months old, when developmental delay, photophobia, myoclo nic \201 ts, hyperacusis and irritability occur. Ophthalmoscopy: cherry-red spot at macu- la. Death at 3 \200\2235yrs of age. Prenatal diagnosis may be made by amniocentesis. Tolo sa \200\223Hunt syndrome Painful ophthalmoplegia + ipsilateral ocular motor nerve palsies, from non-speci \201 c granulomatous in \202 ammation in the cavernous sinus, superior orb ital \201 ssure, or orbit. Maxillary sinusitis may trigger it. MRI may show enhancement o f one cavernous sinus. Corticosteroids may cure. 159,160 s u o m y n o p e l a u s u n U Treacher \200\223Collins syndrome Autosomal dominant Lower lid notching, oblique palpebral \201 s- sures, \202 attening of malar bones hypoplastic zygoma. If these are associa ted with mandibular defects, ear defects, and deafness, it is called Franceschetti \200\231 s synd. Cause: TCOF1 gene mutations. Reconstructive surgery is an option.161 Turner \200 \231s syndrome (X0 monosomy or mosaic, eg 45,X/46,XX or 45,X/47,XXX; un- correlated with \200\200maternal age). Prevalence: 1 : 2500 girls. Signs: Short stature (eg \200\205130cm, but depends on mother \200\231s height);162 hyperconvex nails; wide car- rying angle (cubi tus valgus); broad, shield-shaped chest; hypoplastic breasts/ lack of secondary sexual feat ures (but pregnancy is possible);163 inverted (not always widely spaced)164 nipples; ptosis ; nystagmus; webbed neck; low poste- rior hairline;165 coarctation of the aorta; left heart defects; leg lymphoedema. Gonad dysgenesis (streak ovary)/absent and puberty may not occur . Typical mode of death: Heart disease. \201\227: Somatropin (human GH; eg 0.6 \200\2232U/ kg/wk SC, or in divided nightly doses) adds a median of 5.1cm to \201 nal stature (6.4cm if GH + oxandrolone \211 0.1mg/kg/day); don \200\231t give if epiphyses are fused. NB: GH prolongs the normal state of insulin resistance seen in puberty (resultant hyperinsulinaemi a may \200\200anabolic eff ects of insulin on protein metabolism in puberty). 166 If hypog onadic, HRT, eg 2mg estradiol valerate + levonorgestrel 75 g at night, can start at 13yrs. Ulysses syndrome After the Trojan war, Ulysses (the Latin name for Odys- seus), King of It haca, had many perilous and perhaps pointless adventures be- fore he returned to his starti ng place. Similarly, many of our incurable patients start out with a problem, and end with the same problem, after many risky and futile tests have advanced their case not one jot, a s we have not had the courage to say: \200\234Let \200\231s not do anything \200\235. It i s always easier to do new scans or daring operations, and Ulysses syndrome describes this s uper \202 uity. But there is an ambiguity here: \200\234Ithaca has given you the beautifu l voyage If you \201 nd her poor, Ithaca has not cheated you \200 \200\235 Why not? Be cause the journey teach- es patients the one thing that has eluded us: namely wisdom. Konst antinos Kava \201 s; Ithaca Von Gierke \200\231s syndrome (type 1a glycogen storage diseas e; GSD 1a) Autosomal re c e s s i ve Glucose-6-phosphatase is low. GSD 1a is the severest g lycogenosis. \201\231: Muta- tion analysis of G6PC gene. GS D1a accounts for 20% of glycog enoses in some centers . 168 Signs: Hepatomegaly/renomegaly, growth retardation, hypogly- c aemia, lactic acidaemia, hyperuricaemia, failure to thrive, lumbar lordosis, dydlipidaemia, adiposity, xanthomata over joints and buttocks, bleeding ten- dency, and delayed tooth eru ption. 169 Complication: Hepatic adenoma; hepa- tocellular cancer. 170 Werner \200\231s syn drome (WS; progeria) Autosomal re c e s s i ve WS is characterized by precocious ageing aft er a shallow puberty (no growth spurt), with bird-like pinched nose, loss or graying of hai r, cataracts, skin atrophy/ulcers, \200\200peripheral fat, dyslipid- aemia, and diabetes. 171 The complex molecular and cellular phenotypes of WS involve features of genomic instabi lity and accelerated replicative senescence. The gene involved (WRN) has been cloned, and i ts gene product (WRNP) is a hel- icase. Helicases play important roles in a variety of DNA transactions, including DNA replication, trans cription, repair, and recombination, and in WS unwinding of DNA pairs is disordered.172 \201\227: Pioglitazone may reduce insulin resi stance.173 Winkler \200\231s disease p538. Wiskott \200\223Aldrich syndrome (WAS) is a seve re X-linked primary immunode \201 - ciency (p198) with eczema, recurrent infections, autoi mmune disorders, IgA nephrop athy haematopoietic neoplasia. Platelets are too few and to o small. Without marrow transplant, most die before adulthood. WAS protein gene mutations a lso cause X-linked thrombocytopenia, intermittent thrombocyto- penia, and neutropenia.164 P renatal diagnosis: Direct gene analysis with sin- gle-strand conformation polymorphism (SSC P), and hetero-duplex formation (HD).165 \201\227: Antibiotics IV immunoglobulin for in fections. Hematopoietic stem cell transplant is 1st choice therapy. Gene therapy is awaited . 655 s e m o r d n y s s u o m y n o p e l a u s u n U Association: Crohn \200\231s disease. 167 656 11 Orthopedics and trauma Orthopedics Necks 658 \200\22360 Shoulders 662 \200\2234 Elbows 666 Wrist and hand 668 Back s 670 kyphosis and scoliosis 672 A&E* and associated topics Pain \200\224and children in A&E 718 Glasgow Coma Scale 720 \200 Basic life support 721 Gunshot & penetrating injury 722 Major injury (incl. chest) 724 \200 ABCDE approach to trauma 725 Abdominal injury 726 Head injury 728 Wound management 7 30 Tetanus prevention 730 Burns 732 Smoke inhalation 732 Fractures: reduction, traction & low back pain: 674 management 676 sinister pain 678 Hips 680 \200\2235 Knees 686 \200\22391 Feet 684; 692 \200\2235 Osteomyelitis 696 Bone tumors 698 Congenital disor- complications 734 \200\2238 Complex pain syndrome 739 Trauma to arm and shoulder 740 Elbow, forearm & wrist ders of bone 700 Osteochondritis and fracture 742 \200\2235 similar disor- ders 702 \200\2234 Hand infections & injuries 746 \200\2239 Pelvic fractures 750 Hip and femur injuries 752 Cl assifying open fractures 753 Lower leg injuries 754 Ankle and foot injuries 756 Face and ne ck injuries 758 Nerve and artery injuries 760 Dermatomes & nerves 762 Brachial plexus injur ies 764 \200 Spinal cord injuries 766 \200\22375 Vegetative states 776 Does he need a radi ograph/CT? 778 Emergency Department use 780 Bites, stings, foreign bodies 782 Minor procedu res 784 Drowning 786 Heat exhaustion 788 Electric shock injuries 789 Soft tissue & sports injury 705 Joint replace- ment 706 Joint injection and aspiration 708 \200\22311 Tendons 712 Nerve compression (carpal tunnel etc) 714 Overuse injuries 715 Testing peripheral nerves 716 Fig 1. When the spi- ral meets the helix, the orthopod gets his \201 x. Relevant pages in other chapters Pediatrics: ch 2; rheumatology OHCM p540. Sources/further reading Internet: www.worldortho.com; www.wheelessonline.com1 secure.facs.org/trauma/atls/i nformation.html; www.anatomy.tv; www.e-anatomy.org; the image bank at: www.trauma.org Books: Practical Fracture Treatment, 4th ed, McRae and Es ser, ISBN 0443070385; Advanced Trauma Life Support (ATLS ) Manual, 7th ed; ISBN 18806961 42. 1 \200\207Many detailed treatments are described in this chapter, and it is not envisaged that the in- experienced doctor will try them out except under appropriate supervision. The importance of enlisting early expert help (either at once or, if appropriate, by calling t he patient back to the next morning \200\231s clinic) cannot be overemphasized. We thank James Hopkinson-Woolley and Winnie Chen and James Sewell our Specialist Readers fo r this chapter, and Fabio Conteduca for permission to use the image in \201 gure 1 \200 \224and Dr Tom Turmezei for his masterful commentaries on the many images he supplied. 657 Remain in light \200 \200\207It \200\231s better to ask than to remain in the dark; see p 701 for bone & joint types. ankylosis arthro- arthrodesis arthropathy arthroplasty arthrosc opy articular \200 Stiff ening of a joint with \201 brous or bony union across it Relating to a joint (pre \201 x) The surgical fusion of a joint A pathological process occurring within a joint Crea tion of an arti \201 cial joint (eg total hip replacement) Minimally invasive ( \200\230ke yhole \200\231) joint inspection/surgery Relating to a joint surface or capsule; extra-arti cular = outside the joint capsule; intra-articular = within the joint capsule Of a fracture , contained totally inside the body (not open) closed Of a fracture, having more than 2 par ts comminuted multifragmentary Of a fracture, having several discernible (and countable) a m u a r t d n a s c i d e a p o h t r O parts; may be preferred to \200\230comminuted \200\231 by some For axonotmesis, neurotmesi s and neurapraxia, see p760 Of fractures: having any communication with the outside world S urgical cutting, wedging, and then realignment of a bone The anterior aspect of the wrist a nd hand (preferred to volar) For physis, epiphysis, etc., see p683 nerve injuries open osteotomy palmar -physis pseudarthrosis A false joint across which movement can occur in a bone radicle (radiculo-) Nerve \201 bres that come together to form a spinal nerve root r eaming spondylo- spondylolisthesis Slippage (Greek olisthos = slippery) of one vertebra for - Surgical widening the medullary cavity of a bone Relating to a vertebra (pre \201 x; from Greek) ward on top of the other A defect in the pars interarticularis of a vertebra Term used for generalized degenerative disease of the spine Partial dislocation of a joint \200\224as opp osed to full dislocation Means \200\230twisted neck \200\231 (from Latin) \200\224see p660 . Deformity of part of a limb laterally from the normal axis Deformity of part of a limb me dially from the normal axis spondylolysis spondylosis subluxation torticollis valgus varus *A&E nomenclatures A&E stand s for Accident & Emergency; the word \200\230accident \200\231 is often dropped, and emerg ency medicine has emerged as a specialty in its own right \200\224which centers on the \200\230knowledge and skills required for the prevention, diagnosis, and management of the acute and urgent aspects of illness and injury aff ect- ing patients of all age grOUPs with a full spectrum of physical and behavioral disorders. It is a specialty in which time is c ritical \200\231.1 Principles of orthopedic examination Going through clinical examination with an expert is the best way to learn, but this experience can be reinforced by taking pr inciples and background reading with you into the arena. Most orthopedic examinations can b e de- veloped on the following structure, whether for hip, elbow, ankle 1 For each of: \200 Skin \200 Soft tissues \200 Bone 2 Do the following: \200 Look \200 Feel \200 Then, move the limb: 3 Then remember to test: \200 Ligaments \200 Neurovascular status \200 Any special te sts, eg: \200 knee meniscal tests \200 hip \201 xed \202 exion deformity. actively \200 passively (the Dr does the work) \200 versus resistance. \200\207Remember to examine one joint above and one joint below the joint in question, ie for the hip, examine the knee and lumbar spine. This will uncover any referring pathology. When thinking of movement limitation: active loss = neuromuscular de \201 cit; passive los s = bony or soft tissue impediment. The neck \200 If you suspect a cervical spine injury, immobilize the neck with hard collar , sandbags,1 and tape. NB: if very restless, use hard collar only, as otherwise the neck is vulnerable when the body moves on an immobilized head. Examination The posture of the neck and any bone tenderness (midline and over the spinous process- es) are noted. If safe to r emove collar, check the range of movements: \202 exion & extension (mainly at- lanto-occi pital joint); rotation (mainly atlanto-axial joint); lateral \202 exion (whole of cervica l spine). Rota- tion is the movement most commonly aff ected. Examine arms: test for root l esions (see MINIBOX); test the re \202 exes: (biceps C5; brachioradialis C6; triceps C7). Motor nerve roots and dermatomes are given on p716 and p762. If cord compression is suspect ed examine the lower limbs for signs of this (p770), eg upgoing plantars, hyperre \202 exi a. The main sites of injury are C6 & 7, followed by C2. 10% of C-spine fractures will have another spine fracture elsewhere, so always examine the whole spine. \200\207Take neurolo gical signs very seriously. Imaging In minor trauma use the NEXUS or Canadian C-spine rule to decide if an x-ray is required.2 Major trauma may need CT as \201 rst-line imaging (p7 79).3 When examining the image, follow 4 simple steps (ABCS): 1 Alignment: Check alignment of the following: \200 Anterior vertebral bodies; \200 Posterior vertebral bodies \200 Posterior spinal canal \200 Spinous processes ( \201 g 1). \200 A step >3mm is abnor mal (<25%=unifacet; >50%=bifacet dislocation). \200 Atlas \200\223dens interval (ADI) \200\224normal if <3mm (adults) or <5mm (children). \200 40% of <7-yr-olds have anterior displacement C2 on C3 (in this pseu- 658 \200 For root lesions, test: \200 C5: shoulder abduction \200 C6: elbow \202 exion \200 C7: elbow extension \200 C8: \201 nger \202 exion (grip) \200 T1: \201 nger abduc tion a m u a r t d n a s c i d e a p o h t r O do-subluxation the posterior spinal line is maintained). 2 Bone contour: Trace around each vertebra individually. Anterior/posterior height diff erence of >3mm (implies wedge fracture). In general <25% dif f erence is stable and >25% diff erence is unstable. \200 Pedicles (hangman \200\231s #, \201 g 4) & spinous processes (clayshoveller \200\231s #). \200 Avulsion fractures of t he vertebral body (teardrop #). 3 Cartilages: The disc space margins should be parallel (>11 is abnormal). 4 Soft tissues : Check the soft tissue shadows: Retropharyngeal \200\224C1 \200\223C3 <7mm; C4 \200\223C7 <22mm/1 vertebral body ( \201 g 2). \200 Spinous process separation (interspinous ligament rupture). Spiral CT can help d iagnose fractures here.4 \200\207All 7 cervical vertebrae must be seen, along with the c7 \200\223T1 junction: do n ot accept an incomplete image \200\224a \200\230swimmers \200\231 view of C7 \200\223T1 ma y be needed. \200\207A cross-table lateral in the best hands will still miss at least 15% of injuries. Other views and investigations \200 Open mouth \200\230peg \200\231 view (O MV, \201 g 3) for suspected odontoid peg fractures and C1 fractures (total lateral mass overhang of C1 on C2 should be <8mm). \200 CT is used to image areas not adequately assessed on plain \201 lms (p779). \200 MRI is vital for as sessing ligamentous disruption, disc prolapse, and the neu- ral elements (spinal cord and n erve roots), all of which can only be inferred from CT and plain radiography. Whole spine a ssessment is best.