DOWN SYNDROME

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visited=11%2F23%2F2009><table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=110 BGCOLOR="#666699" TEXT="#080000" bgproperties="fixed" background="04a00840erlcjm.gif"> <div> <FONT SIZE="5" COLOR="#FFFFFF" FACE="Arial" ><B>pediatryPART I</B></FONT><B>     |     </B><A HREF="index.htm" TARGET="_top" TITLE="pediatryPART I"><U><B>home</B></U></A></div> <div> <A HREF="id31.htm" TARGET="_top" TITLE="PEDIATRIC PEARLS FOR THE USMLE"><U>PEDIATRIC PEARLS FOR THE USMLE</U></A>   |   <A HREF="id48.htm" TARGET="_top" TITLE="pearls pediatry 2"><U>pearls pediatry 2</U></A>   |   <A HREF="id18.htm" TARGET="_top" TITLE="general"><U>general</U></A>   |   <A HREF="id34.htm" TARGET="_top" TITLE="appendiceal colic"><U>appendiceal colic</U></A>   |   <A HREF="id35.htm" TARGET="_top" TITLE="ATOPIC DERMATITIS"><U>ATOPIC DERMATITIS</U></A>   |   <A HREF="id19.htm" TARGET="_top" TITLE="Stuttering"><U>Stuttering</U></A>   |   <A HREF="id20.htm" TARGET="_top" 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disease"><U><B>infectious disease</B></U></A></div> <div> <A HREF="id32.htm" TARGET="_top" TITLE="HEMORRHAGIC DISEASE IN A NEW BORN"><U><B>HEMORRHAGIC DISEASE IN A NEW BORN</B></U></A></div> <div> <A HREF="id33.htm" TARGET="_top" TITLE="OPTIC NERVE GLIOMA"><U><B>OPTIC NERVE GLIOMA</B></U></A></div> <div> <A HREF="id36.htm" TARGET="_top" TITLE="New Born Assessment "><U><B>New Born Assessment </B></U></A></div> <div> <A HREF="id38.htm" TARGET="_top" TITLE="laryngomalacia"><U><B>laryngomalacia</B></U></A></div> <div> <A HREF="id39.htm" TARGET="_top" TITLE="CRANIOSYNOSTOSIS "><U><B>CRANIOSYNOSTOSIS </B></U></A></div> <div> <A HREF="id40.htm" TARGET="_top" TITLE="DANDYWALKER MALFORMATION "><U><B>DANDY-WALKER MALFORMATION </B></U></A></div> <div> <A HREF="id41.htm" TARGET="_top" TITLE="DEJERINESOTTAS DISEASE "><U><B>DEJERINE-SOTTAS DISEASE </B></U></A></div> <div> <B>DOWN SYNDROME </B></div> <div> <A HREF="id43.htm" TARGET="_top" TITLE="Respiratory Syncytial Virus (RSV)"><U><B>Respiratory Syncytial Virus (RSV)</B></U></A></div> <div> <A HREF="id44.htm" TARGET="_top" TITLE="FABRY DISEASE "><U><B>FABRY DISEASE </B></U></A></div> <div> <A HREF="id45.htm" TARGET="_top" TITLE="PRADERWILLI SYNDROME "><U><B>PRADER-WILLI SYNDROME </B></U></A></div> <div> <A HREF="id37.htm" TARGET="_top" TITLE="new born fun"><U><B>new born fun</B></U></A></div> <div> <A HREF="id46.htm" TARGET="_top" TITLE="RETT SYNDROME "><U><B>RETT SYNDROME </B></U></A></div> <div> <A HREF="id47.htm" TARGET="_top" TITLE="Alexander Disease"><U><B>Alexander Disease</B></U></A></div> <div> <A HREF="id49.htm" TARGET="_top" TITLE="leukemia"><U><B>leukemia</B></U></A></div> <div> <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U><B>Contact Me</B></U></A></div> </td> <td valign="top" height=370 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> DOWN SYNDROME </div> <div> DEFINITION:</div> <div> A chromosomal disorder resulting in a syndrome characterized by specific dysmorphic features (facies) and organ malformations. </div> <div> EPIDEMIOLOGY:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">incidence: 1/800 live births </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">75% of fetuses with Trisomy 21 abort spontaneously </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">most common autosomal chromosomal disorder causing mental retardation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">age of onset: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">newborn </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">risk factors: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">increased maternal age (although 80% are born to mothers <35 years) </div> <div> HISTORY:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1865 - John Langdon Down </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">first detailed description </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1930 - Brewster and Cannon </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">first to report an association between Down's & acute leukemia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1954 - Schunk and Lehman </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">first to report an association between Down's & transient leukemia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1959 - Lejeune </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">first to associate Down's with Trisomy 21 </div> <div> GENETICS/PATHOGENESIS:</div> <div> 1. Genetics</div> <div> 1. Trisomy 21 (95%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">due to non-disjunction during meiosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">80-90% due to maternal non-disjunction </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">10-20% " paternal " </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1% recurrence risk </div> <div> 2. Unbalanced Translocation (3-4%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">50% are sporadic (de novo) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">50% are due to a balanced translocation in one parent </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">recurrence risk: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">100% in parent with a 21:21 translocation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">16% in mother with a 21:acrocentric chrom. transloca. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">5% in father " </div> <div> 3. Mosaicism (1-2%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">due to nondisjunction after meiosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? recurrence risk </div> <div> 2. Pathogenesis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trisomy of only the bottom 1/3 of chromosome 21 is sufficient to account for Down's phenotype </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chrom. 21: the 800 genes in the 21q22 band appear to be those responsible for the pathogenesis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">trisomy results in a 50% increased "dose" of certain proteins: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. SOD-1 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">superoxide dismutase </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">protects cells from oxygen-containing free radicals </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role in MR and accelerated rate of aging </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. Gart </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">phosphoribosylglycinamide synthetase </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">involved in purine synthesis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? elevated purines -> mental retardation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3. Ets-2 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">an oncogene </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role in acute myelogenous leukemia M2 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">4. Amyloid Beta Protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">major component of neurofibrillary plaques </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? pathogenesis in Alzheimers </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">5. Alpha-A-crystallin Protein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">structural component of lens of eye </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role in formation of cataracts, Brushfield spots </div> <div> 3. Pathogenesis (of Transient Leukemia)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">proposed mechanisms: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. spontaneously remitting leukemic clone </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. stress (infections, CHD, etc.) -> over reaction of myeloid elements </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3. delay in WBC differentiation which resolves spontaneously as maturation progresses post-natally </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">4. ineffective regulation of myeloporesis due to delayed maturation of the myeloid and other bone marrow elements </div> <div> CLINICAL FEATURES:</div> <div> 1. Principle Clinical Features in the Newborn (Clin Peds 5:4 (1966))</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">100% contain at least 4 of these </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">89% contain at least 6 of these: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">flat facial profile (90%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">poor Moro reflex (85%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">infantile hypotonia (80%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hyperflexibility of joints (80%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">excess skin on neck (80%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">slanted palpebral fissures (80%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dysplasia of pelvis (70%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">anomalous auricles (60%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">dysplastic 5th midphalanx (60%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">45 simian crease (45%) </div> <div> 2. Diagnostic Index (J. Peds. 100(6): 903 (1982))</div> <div> 1. Dermatoglyphic Traits</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hallucal pattern </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">forefinger pattern </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">palmar triradius </div> <div> 2. Physical Traits</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ear length </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">internipple distance ratio </div> <div> 3. Clinical Findings</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">wide-spaced first toe </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">excess skin on back of neck </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">brushfield spots </div> <div> 3. Neurologic Manifestations</div> <div> 1. Hypotonia (100%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">at birth, in infancy, and as a toddler </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may delay motor milestones but improves with age </div> <div> 2. Seizures (5-10%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">generalized, myoclonic most common type </div> <div> 3. Learning Disabled</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">borderline to moderate IQ range (from 80 -> 40) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">processing problems: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">better at visual than auditory processing </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">better at simultaneous than sequential processing </div> <div> 4. Global Developmental Delays</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">gross motor due to hypotonia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fine motor " </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">speech and language delay </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">75% have an expressive language disability </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">behavioural problems </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">aggression, depression, inappropriate </div> <div> 5. Alzheimers</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may affect 15-20% of adults with Down's </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mean age of onset is 51 years (range 46-57 years) </div> <div> 4. Respiratory Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">increased incidence of pulmonary hypoplasia and elevated pulmonary vascular resistence (+/- congenital heart defects) may lead to an increased risk of: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">respiratory tract infections </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">acute and chronic airway obstruction </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sleep apnea (small airways, large tonsils/adenoid, obesity) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">cor pulmonale </div> <div> 5. Cardiovascular Manifestations (40%)</div> <div> 1. Structural Anomalies</div> <div> 1. Endocardial Cushion Defects</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">complete AV canal (49%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">VSD (22%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ASD(secundum)- 14% </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ASD(primum) - 8% </div> <div> 2. Others</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3 PDA (3%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ToF (3%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">AV valve malformation (prolapse) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">aberrant subclavian artery </div> <div> 2. Complications</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">elevated pulmonary blood flow -> irreversible pulmonary hypertension -> cor pulmonale </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">structural anomalies and complications are usually detected in the newborn period or in the first 6 weeks of life </div> <div> 6. Gastrointestinal Manifestations (12%)</div> <div> 1. Structural anomalies</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">duodenal atresia most common problem (+/- polyhydramnios, double bubble) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">others: TEF, annular pancreas, Meckel's diverticulum, Hirschsprung's disease, imperforate anus </div> <div> 2. Complications</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">vomiting (bilious), constipation, failure to thrive, feeding difficulties and intolerance </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">structural anomalies and complications are usually detected in the newborn period or in the first 6 weeks </div> <div> 7. Genitourinary Manifestations</div> <div> 1. Structural Anomalies</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Kidney Malformation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">uteropelvic junction (UPJ) obstruction with hydro-nephrosis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">alterations in structure or maturation of parenchymal structures </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. External Genitalia Malformation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">25-50% of males have hypospadias </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">5% of males have undescended testes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">small penis and scrotum </div> <div> 8. Hematologic Manifestations</div> <div> 1. Leukemia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">risk is 10-30x that of general population </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">in newborns AML > ALL (2-4:1) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">in children ALL > AML (2:1) </div> <div> 2. Transient (Congenital) Leukemia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">presence of a large number of blasts (megakaryoblasts) in the peripheral blood </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may be variable leukocytosis +/- thrombocytopenia +/- anemia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">clinically may be associated with lymphadenopathy and/or hepatomegaly/hepatosplenomegaly </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">100% spontaneous remission rate within 1st weeks of life </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">occurs exclusively in Down's (82% in newborn period) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">some cases may give rise to acute megakaryoblastic leukemia (AMKL) or other forms of leukemia during the first 3 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">- diagnosis is retrospective </div> <div> 3. Autoimmune Disorders</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">higher than average likelihood of developing: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">thyroiditis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">alopecia areata (in 10-15%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diabetes mellitus </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rheumatoid-type arthropathy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">autoimmune hemolytic anemia </div> <div> 9. Endocrine Manifestations</div> <div> 1. Thyroid Dysfunction (15%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Hypothyroidism </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">often due to lymphocytic thyroiditis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">most present after the 1st decade </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may appear in conjunction with diabetes mellitus, pre-cocious sexual maturation or hypoparathyroidism - may have congenital hypothyroidism </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hyperthryoidism & euthyroid thyroiditis can also occur </div> <div> 2. Growth Disorders</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Short Stature </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">both M & F at or near the 3rd % of general population </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">diminished growth velocity can occur at a variety of times (i.e., decreased adolescent growth spurt) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">there are specific growth charts for Trisomy 21 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. Obesity </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">especially at 2-3 years, 12-13 years, and in adult life </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">a common problem </div> <div> 3. Sexual Maturation and Development</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Males </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">normal but fertility very rare </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">25-50% have undescended testes </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">5% have hypospadias </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">testes may be histologically abnormal </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. Females </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">normal sexual maturation and development </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">menstruation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">normal age of onset (no delay in onset of puberty) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">normal menses </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">fertility </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">definite ovulation in 40%, probable in 15%, possible in 15% </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">abnormal follicular development is common </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pregnancy is possible with a 50% chance of Trisomy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">21 occurring in the infant </div> <div> 10. Dermatologic Manifestations</div> <div> 1. Dry Skin (90%)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">with secondary itching, eczema, and infections (i.e., recur-rent follicular skin infections) </div> <div> 2. Syringomas</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">benign sweat gland tumors </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">F > M; onset at beginning of puberty </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">yellow or skin-coloured, soft 2-3 mm raised papules occur-ring singly or in groups </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">most commonly found around eyes but also on neck and thor-acic, axillary, umbilical, and pubic areas </div> <div> 3. Others</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">alopecia areata (in 10%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">rapid aging of skin </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">increased risk of sunburn </div> <div> 11. Musculoskeletal Manifestations</div> <div> 1. Cervical Spine Problems</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">1. Atlantoaxial Instability (14%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">incidence: 1/3000 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2. Spinal Cord Compression (1-2%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">with persistent neck pain, loss of bladder or bowel control, changes in sensation, long tract signs </div> <div> 2. Others</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bony anomalies of the cervical spine </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">subluxation or dislocation of hips and/or knees </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">pronation of feet at ankles, pes pannus, short broad hands, short sternum, decreased acetabular and iliac angle (CDH, dysplastic hips), see "Clinical features in Newborn" </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypotonia & ligamentous laxity predisposes to these problems </div> <div> 12. Ocular Manifestations</div> <div> 1. Major</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">congenital nystagmus or alternating esotropia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">congenital cataracts and glaucoma </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">60% with strabismus </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">50% with refractive errors </div> <div> 2. Minor</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">epicanthal folds, oblique palpebral fissures </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">blepharitis, keratoconus, Brushfield spots </div> <div> 13. Oral and Dental Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">delays and alterations in the sequence of tooth eruption </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">100% with malocclusions (mandibular overjet, post. cross bite) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">60% with relative macroglossia </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">50% with missing teeth </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">37-60% with fissuring tongue, enlargement of vallate papillae </div> <div> 14. Otorhinolaryngologic Manifestations</div> <div> 1. Recurrent Otitis Media</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">75% with sensorineuronal conductive hearing loss due to an accumulation of fluid in the middle ear space </div> <div> 2. Midface Hypoplasia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nasolacrimal duct obstruction (in 20%) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">obstructive sleep apnea </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sinusitis and purulent rhinitis </div> <div> INVESTIGATIONS:</div> <div> 1. Prenatal Screening/Diagnosis</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">chorionic villus sampling at 9-12 weeks </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">amniocentesis at 16-18 weeks </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">indications for: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">advanced maternal age (>35 years) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">previous child with Trisomy 21 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">balanced translocation in parent </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">prenatal U/S findings suggestive of Trisomy 21 </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">altered maternal serum markers </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">decreased alpha fetoprotein </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">" human chorionic gonadotropin </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">" unconjugated estriol (uE3) </div> <div> 2. Imaging Studies</div> <div> 1. Cardiac</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">2D-Echo, chest x-ray, EKG </div> <div> 2. Gastrointestinal</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">abdominal x-ray, barium swallow/enema </div> <div> 3. Renal</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">renal ultrasound </div> <div> 4. Skeletal X-Rays</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bone age for short stature </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">C-spine - an atlanto-dens space >5 mm is suggestive of atlantoaxial instability </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">sinusitis </div> <div> 3. Serum</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">compensated respiratory acidosis (due to COPD) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">elevated urea, creatinine, uric acid, decreased creatinine and uric acid clearance </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CBC with blasts </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">TSH, T3, T4, thyroid antibodies </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? GH stimulation tests </div> <div> 4. Others</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">EEG (hypsarrhythmias) </div> <div> MANAGEMENT:</div> <div> 1. Neurologic Manifestations</div> <div> 1. Seizures</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurology consult, EEG, anticonvulsant medications </div> <div> 2. Learning Disabilities</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">teaching methods which emphasize visual over auditory information </div> <div> 3. Developmental Delays</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">early intervention </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">gross/fine motor - physiotherapy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">speech/language - total communication techniques (signing or computers), speech therapy, special education </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">behaviour - mental health assistance, family counsel </div> <div> 2. Respiratory Manifestations</div> <div> 1. Sleep Apnea</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">decrease weight, repositioning during sleep, nasal CPAP, remove tonsils and adenoids </div> <div> 2. Cor Pulmonale</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">early surgical correction of congenital heart disease (CHD) </div> <div> 3. COPD</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bronchodilators/steroids </div> <div> 3. CVS Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">all Down's patients should have a Cardiology consult and an echo done within the first few weeks of life </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">surgical correction of CHD </div> <div> 4. Gastrointestinal Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">surgical correction of malformations </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">treat functional problems, i.e., constipation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">feeding team for problems </div> <div> 5. Genitourinary Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">follow serum urea, creatinine, uric acid </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">follow uric acid and creatinine clearance rates </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role of imaging studies for screening for anomalies </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">surgical correction of hypospadia, undescended testes </div> <div> 6. Hematologic Manifestations</div> <div> 1. Leukemia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">state of the art therapy noting increased risk of infec-tion and sensitivity to anti-folate chemotherapy </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">lower remission rate and a higher mortality with ALL in </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Down's than general population </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">similar remission rate and mortality with AML in Down's and general population </div> <div> 2. Transient Leukemia</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">moniter blasts in peripheral blood </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">spontaneous remission but risk of leukemia (ie. AMKL) </div> <div> 3. Autoimmune Disorders</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">screen for manifestations i.e., TSH, blood sugar </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">? role of pneumococcal and influenzae vaccines </div> <div> 7. Endocrine Manifestations</div> <div> 1. Thyroid</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">screen for clinical s/s of hypothyroidism (dry hair/skin, lethargy, cold intolerance, constipation, hoarse voice) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">screen TFT (TSH, T3, T4) annually +/- thyroid antibodies </div> <div> 2. Growth</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">moniter growth on charts for Down's </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">true GH deficiency is rare but may respond to GH supplements </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">obesity - caloric restriction, increase activity/exercise </div> <div> 3. Reproduction</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">birth control and reproductive health issues need to be addressed (i.e., sterilization) </div> <div> 8. Dermatology Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">moisturizers, hypoallergenic creams for dry skin </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">steroid creams for eczema </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">topical or systemic antibiotics for infection </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">preventive measures to avoid sunburn </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">topical steroids, minoxidil for alopecia areata </div> <div> 9. Musculoskeletal Manifestations</div> <div> 1. C-Spine</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">see the Canadian Down's Society Guidlines </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">initially assessed at 2-4 years and repeated between 8-10 years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">earlier assessment if indicated - neurologic findings: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">loss of motor skills </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">asymmetric hypertonicity in lower limbs </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">increased clumsiness or tripping </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">widely-spaced stiff-legged gait </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">any upper motor neuron signs </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">loss of fine motor skills </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">torticollis, neck pain, headaches </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">if abnormal then must restrict activities - tumbling, div-ing, butterfly, collision sports </div> <div> 2. Spinal Cord Compression</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">may require surgical stabilization (skeletal fixation) of cervical spine </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ortho, neuro, neurosurg consults </div> <div> 10. Ocular Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">initial screen should occur in early infancy with follow-up at </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">18 months and 5 and 15 years </div> <div> 11. Oral and Dental Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">routine preventive dental care </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">relative macroglossia may be corrected by oral or plastic sur-gery if indicated </div> <div> 12. Otorhinolaryngologic Manifestations</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">audiologic evaluation by sound field testing or auditory brain-stem responses (ABR) should begin at 6 months and be repeated q6-12m during the preschool years </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">antibiotics for recurrent OM, sinusitis, or purulent rhinitis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">myringotomy tubes for recurrent otitis media (OM) </div> <div> 13. Genetics</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">genetic counselling if plans for another child </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">80% survive to age 30 or beyond </div> <div> The Chromosomes</div> <div> Chromosomes are thread-like structures composed of DNA and other proteins. They are present in every cell of the body and carry the genetic information needed for that cell to develop. Genes, which are units of information, are "encoded" in the DNA. Human cells normally have 46 chromosomes which can be arranged in 23 pairs. Of these 23, 22 are alike in males and females; these are called the "autosomes." The 23rd pair are the sex chromosomes ('X' and 'Y'). Each member of a pair of chromosomes carries the same information, in that the same genes are in the same spots on the chromosome. However, variations of that gene ("alleles") may be present. (Example: the genetic information for eye color is a "gene;" the variations for blue, green, etc. are the "alleles.") </div> <div> Human cells divide in two ways. The first is ordinary cell division (<B>"mitosis"</B>), by which the body grows. In this method, one cell becomes two cells which have the exact same number and type of chromosomes as the parent cell. The second method of cell division occurs in the ovaries and testicles (<B>"meiosis"</B>) and consists of one cell splitting into two, with the resulting cells having half the number of chromosomes of the parent cell. So, normal eggs and sperm cells only have 23 chromosomes instead of 46. </div> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="627" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 206 WIDTH="358"><div> This is what a normal set of chromosomes looks like. Note the 22 evenly paired chromosomes plus the sex chromosomes. The XX means that this person is a female. The test in which blood or skin samples are checked for the number and type of chromosomes is called a <B>karyotype</B>, and the results look like this picture. </div> </tD> <tD VALIGN=CENTER><NOBR><div> <IMG SRC="0e008c80.gif" border=0 width="264" height="200" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> </tR> </TABLE></div> <div> Many errors can occur during cell division. In meiosis, the pairs of chromosomes are supposed to split up and go to different spots in the dividing cell; this event is called "disjunction." However, occasionally one pair doesn't divide, and the whole pair goes to one spot. This means that in the resulting cells, one will have 24 chromosomes and the other will have 22 chromosomes. This accident is called "<B>nondisjunction</B>." If a sperm or egg with an abnormal number of chromosomes merges with a normal mate, the resulting fertilized egg will have an abnormal number of chromosomes. In Down syndrome, 95% of all cases are caused by this event: one cell has two 21st chromosomes instead of one, so the resulting fertilized egg has three 21st chromosomes. Hence the scientific name, <B>trisomy 21</B>. Recent research has shown that in these cases, approximately 90% of the abnormal cells are the eggs. The cause of the nondisjunction error isn't known, but there is definitely connection with maternal age. Research is currently aimed at trying to determine the cause and timing of the nondisjunction event.</div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" ><IMG SRC="0e143c80.gif" border=0 width="323" height="200" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></FONT>Three to four percent of all cases of trisomy 21 are due to <B>Robertsonian Translocation</B>. In this case, two breaks occur in separate chromosomes, usually the 14th and 21st chromosomes. There is rearrangement of the genetic material so that some of the 14th chromosome is replaced by extra 21st chromosome. So while the number of chromosomes remain normal, there is a triplication of the 21st chromosome material. Some of these children may only have triplication of part of the 21st chromosome instead of the whole chromosome, which is called a <B>partial trisomy 21</B>. Translocations resulting in trisomy 21 may be inherited, so it's important to check the chromosomes of the parents in these cases to see if either may be a "carrier." </div> <div> The remainder of cases of trisomy 21 are due to <B>mosaicism</B>. These people have a mixture of cell lines, some of which have a normal set of chromosomes and others which have trisomy 21. In cellular mosaicism, the mixture is seen in different cells of the same type. In tissue mosaicism, one set of cells, such as all blood cells, may have normal chromosomes, and another type, such as all skin cells, may have trisomy 21</div> <bR> <bR> <bR> <bR> <div> <B><U>Genes that may have input into Down syndrome include: </U></B></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Superoxide Dismutase (SOD1)</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" >-- overexpression may cause premature aging and decreased function of the immune system; its role in Senile Dementia of the Alzheimer's type or decreased cognition is still speculative </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">COL6A1</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may be the cause of heart defects </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">ETS2</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may be the cause of skeletal abnormalities and/or leukemia </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CAF1A</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may be detrimental to DNA synthesis </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cystathione Beta Synthase (CBS)</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may disrupt metabolism and DNA repair </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">DYRK</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may be the cause of mental retardation </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">CRYA1</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may be the cause of cataracts </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">GART</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- overexpression may disrupt DNA synthesis and repair </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">IFNAR</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > -- the gene for expression of Interferon, overexpression may interfere with the immune system as well as other organ systems </FONT></div> <bR> <bR> <bR> <div> Other genes that are also suspects include <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>APP</U></FONT>, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>GLUR5</U></FONT>, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>S100B</U></FONT>, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>TAM</U></FONT>, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>PFKL</U></FONT>, and a few others. Again, it is important to note that <I>no gene has yet been fully linked to any feature associated with Down syndrome</I>. </div> <div> One of the more notable aspects of Down syndrome is the wide variety of features and characteristics of people with trisomy 21: There is a wide range of mental retardation and developmental delay noted among children with Down syndrome. Some babies are born with heart defects and others aren't. Some children have associated illnesses such as epilepsy, hypothyroidism or celiac disease, and others don't. The first possible reason is the difference in the genes that are triplicated. As I mentioned above, genes can come in different alternate forms, called "alleles." The effect of overexpression of genes may depend on which allele is present in the person with trisomy 21. The second reason that might be involved is called "penetrance." If one allele causes a condition to be present in some people but not others, that is called "variable penetrance," and that appears to be what happens with trisomy 21: the alleles don't do the same thing to every person who has it. Both reasons may be why there is such variation in children and adults with Down syndrome.</div> <bR> </td> </tr></table></body>