NeuromuscularSkeletalNeuromuscularSkeletal Dysplasia Dysplasia Disorders Disorders NeuromuscularSkeletal Dysplasia Disorders SkeletalSkeletal Dysplasia Dysplasia Skeletal Dysplasia AboutAbout EGL EGL Genetics Genetics EGLAboutEGL Genetics Genetics EGL specializesGenetics specializes in in genetic genetic diagnostic diagnostic testing, testing, with with ne nearlyarly 50 50 years years of of clinical clinical experience experience and and board-certified board-certified labor laboratoryatory directorsEGLdirectors Genetics and and genetic specializesgenetic counselors counselors in genetic reporting reporting diagnostic out out cases.testing, cases. EGL EGLwith Genet Genet nearlyicsics offers50 offers years a acombined of combined clinical 1000experience 1000 molecular molecular and genetics,board-certified genetics, biochemical biochemical laboratory genetics,directorsgenetics, and and cytogenetics cytogeneticsgenetic counselors tests tests under under reporting one one roof outroof and cases. and custom custom EGL Genet test testingicsing for offersfor all all medically amedically combined relevant relevant 1000 ,molecular genes, for for domesticgenetics, domestic biochemical andgenetics,and international international and cytogenetics clients. clients. tests under one roof and custom testing for all medically relevant genes, for domestic EquallyEquallyand international important important to clients.to improving improving patient patient care care through through quality quality genetic genetic testing testing is is the the contribution contribution EGL EGL Genetics Genetics makes makes back back to to thEquallyteh esc siceine tinimportantfiticfi ca nadn dm m etode idimprovingciacla cl ocmommmu patientnuintiietise.s E. GEcareLG LG eGthroughneenteictisc iss iqualityos noen eo f o ogeneticf nolnyl ya afe fwtestingew c lcinliinc iaiscla d l ithedaigan gocontributionnsotiscti cla lbaobroartaot rEGLoierise t so Geneticst oo poepnelnyl ysmakesh sahraer edback adtaa to t a withwiththe thes ctheie NCBIn NCBItific freelya freelynd m availablee availabledical co mpublic publicmun idatabaseti databasees. EGL GClinVar eClinVarnetic s(> i(>3s 5,0003o 5,000ne o fvariants ovariantsnly a f one won >1700c l>1700inica lgenes) dgenes)iagno ands andtic isla isbalso oalsora ttheo theri eonlys only to laboratoryo plaboratoryenly sha rwithe with da taa a freewithfree online onlinethe NCBI database database freely (EmVClass), available(EmVClass), public featuring featuring database a avariant variant ClinVar classification classification (>3 5,000 variants search search on and >1700and report report genes) request request and interface, isinterface, also the whichonly which laboratoryfacilitates facilitates with a rapidfreerapid interactiveonline interactive database curation curation (EmVClass), and and reporting reporting featuring of ofa variants. variant variants. classification search and report request interface, which facilitates rapid interactive curation and reporting of variants. SkeletalSkeletal Dysplasia Dysplasia SkeletalSkeletal dysplasias dysplasias Dysplasia are are a aheterogeneous heterogeneous group group of of more more than than 450 450 disorders. disorders. Collectively, Collectively, the the incidence incidence of ofskeletal skeletal dysplasiaSkeletaldysplasia isdysplasias isestimated estimated are to ato heterogeneousbe be 1 in1 in 5,000 5,000 births. births.group Skeletal ofSkeletal more dysplasias dysplasiasthan 450 are disorders.are generalized generalized Collectively, disorders disorders the of ofincidencecartilage cartilage andof andskeletal bone, bone, frequentlydysplasiafrequently resultingis resulting estimated in in disproportioned todisproportioned be 1 in 5,000 births.short short stature. Skeletalstature. These dysplasiasThese disorders disorders are generalizedcan can range range greatly disordersgreatly in in severity, ofseverity, cartilage from from andprecocious precocious bone, arthropathyfrequentlyarthropathy inresulting in relatively relatively in disproportionedaverage average stature stature individuals individualsshort stature. to to severe severeThese dwarfism disordersdwarfism canwith with range perinatal perinatal greatly mortality. mortality.in severity, A Avariety fromvariety ofprecocious of complicationsarthropathycomplications in can relativelycan be be associated associated average with staturewith skeletal skeletal individuals dysplasia, dysplasia, to includingsevere including dwarfism orthopedic, orthopedic, with neurologic, perinatalneurologic, auditory,mortality. auditory, Avisual, visual,variety pulmonary, pulmonary,of cardiac,complicationscardiac, renal, renal, and andcan psychological. psychological.be associated with skeletal dysplasia, including orthopedic, neurologic, auditory, visual, pulmonary, cardiac, renal, and psychological. TheThe identification identification of of the the precise precise genetic genetic defect defect is is important important to to permitpermit carrier carrier testing testing and and early early prenatal prenatal diagnosis. diagnosis. MolecularTheMolecular identification analysis analysis is islikely oflikely the to to expandprecise expand thegenetic the clinical clinical defect spectrum spectrum is important of of skeletal skeletal to permitdysplasia dysplasia carrier and and testing may may also also and provide provideearly dataprenatal data relevant relevant diagnosis. to to prognosisprognosisMolecular and andanalysis future future is therapeutic likelytherapeutic to expand intervention. intervention. the clinical spectrum of skeletal dysplasia and may also provide data relevant to prognosis and future therapeutic intervention. SkeletalSkeletal Dysplasia Dysplasia Testing Testing AlgorithmAlgorithm Skeletal Dysplasia Testing Algorithm ClinicalClinical Evaluations Evaluations History:History: time time of of onset, onset, growth growth charts, charts, fractures, fractures, Clinicalother other test test Evaluations re results,sults, involvement involvement of of other other organs, organs,andand family family history history  Exam:History:Exam: dysmorphic dysmorphic time of onset, features, features, growth disproportion disproportion charts, fractures, other test results, involvement of other organs,and family history Exam: dysmorphic features, disproportion

RadiologicalRadiological Assessment- Assessment- Prepubertal Prepubertal skeletal skeletal radiography radiography Genetic RadiologicalGenetic skeletal skeletal surveyAssessment- survey to todetermine: determine: Prepubertal skeletal radiography • Genetic•DisproportionedDisproportioned skeletal surveyor or proportioned proportioned to determine: • •Epiphyseal/metaphyseal/diaphyseal/spinalEpiphyseal/metaphyseal/diaphyseal/spinalDisproportioned or proportioned ossification ossification • Epiphyseal/metaphyseal/diaphyseal/spinal ossification

Proportioned Proportioned Short Short Stature Stature DisproportionedDisproportioned Short Short Stature Stature – – Non-syndromicNon-syndromic Comprehensive ProportionedComprehensive PanelShort Panel Stature Disproportioned Short Stature – Non-syndromic Comprehensive Panel

GeneGene Panel* Panel* Panel*

Disproportionate Disproportionate Short Short IncreasedIncreased Bone Bone Density Density Decreased Decreased Bone Bone Density Density Limb Limb Malformation Malformation DisproportionateStatureStature Short Increased Bone Density Decreased Osteolysis Osteolysis Bone Density Limb Malformation Stature Osteolysis

*Can*Can be be ordered ordered sep sepĂratelyĂrately or or together together *Can be ordered sepĂrately or together ForFor more more information information about about EGL EGL Genetics Genetics and and the the nearly nearly 1000 1000 tests tests we we offer: offer: For more information about EGL Genetics and the nearly 1000 tests we offer: CALLCALL WEB WEB 470.378.2200 470.378.2200CALL eglgenetics.com eglgenetics.com WEB 470.378.2200 eglgenetics.com

NeuromuscularSkeletal Dysplasia Disorders Skeletal Dysplasia Skeletal Dysplasia Next Generation Sequencing Panels EGL Genetics offers a comprehensive 163-gene skeletal dysplasia panel. Five major groups are included in this panel: proportionate short stature; disproportionate short stature; skeletal dysplasias with increased bone density; skeletal dysplasias with decreased bone density osteolysis; and limb malformations. Phenotype-specific gene panels are also available. Genes Included on Skeletal DysplasiaYour Panel* Partner in Genetic Healthcare ACP5 CHSY1 DMP1 FGFR3 IFT140 NEK1 PTPN11 SOST TREM2 ALPL CLCN5 DYM FKBP10 IFT80 NIPBL PYCR1 SOX9 TRIP11 ANKH CLCN7 DYNC2H1 FLNA IHH NKX3-2 RASGRP2 SP7 TRPS1 ANO5 COL10A1 EIF2AK3 FLNB KIF22 NOG RECQL4 SULF1 TRPV4 ARHGAP31 COL11A1 ENPP1 FMN1 KIF7 NOTCH2 ROR2 TBCE TYROBP ATP6V0A2 COL11A2 ESCO2 GALNT3 LEMD3 NPR2 RPGRIP1L TBX15 WDR35 B3GALT6 COL1A1 EVC GDF5 LIFR OBSL1 RUNX2 TBX3 WISP3 B4GALT7 COL1A2 EVC2 GLI3 LMBR1 OSTM1 SALL1 TBX5 WNT3 BMP2 COL2A1 EXT1 GNAS LMNA P3H1 SALL4 TBXAS1 WNT5A BMPR1B COL9A1 EXT2 GORAB LRP4 PAPSS2 SERPINH1 TCIRG1 WNT7A CA2 COL9A2 FAM20C GPC6 LRP5 PCNT SH3PXD2B TCTN3 ZMPSTE24 CANT1 COL9A3 FBLN1 GREM1 MAFB PHEX SHH TGFB1 CASR COMP FBN1 HDAC4 MATN3 PIGV SHOX THPO CC2D2A CRTAP FBXW4 HOXD13 MGP PITX1 SLC25A12 TMEM216 CDH3 CTSK FERMT3 HPGD MKS1 PLOD2 SLC26A2 TMEM67 CDKN1C CUL7 FGF10 HSPG2 MMP13 PPIB SLC34A3 TNFRSF11A CEP290 DDR2 FGF23 ICK MMP2 PRKAR1A SLC35D1 TNFRSF11B CHST14 DHCR24 FGFR1 IFITM5 MMP9 PTH1R SLC39A13 TNFSF11 CHST3 DLX3 FGFR2 MYCN MMP9 PTHLH SMARCAL1 TP63 *Some genes on this panel are associated with additional phenotypes. All genes on the next generation sequencing panel may be ordered separately. Genes included on panels are subject to change.

Test Code Test Name CPT®** Code(s) MM170 Skeletal Dysplasia: Sequencing Panel 81406 (x1), 81407 (x1), 81408 (x1) MD170 Skeletal Dysplasia: Deletion/Duplication Panel 81228 (x1) MM171 Disproportionate Short Stature: Sequencing Panel 81404 (x1), 81405 (x1), 81406 (x1) MD171 Disproportionate Short Stature: Deletion/Duplication Panel 81228 (x1) MM172 Skeletal Dysplasia With Increased Bone Density: Sequencing Panel 81405 (x1), 81408 (x1), 81479 (x1) MD172 Skeletal Dysplasia With Increased Bone Density: Deletion/Duplication Panel 81228 (x1) MM173 Osteogenesis Imperfecta and Decreased Bone Density: Sequencing Panel 81404 (x1), 81405 (x1), 81406 (x1) MD173 Osteogenesis Imperfecta and Decreased Bone Density: Deletion/Duplication Panel 81228 (x1) MM174 Limb Malformation: Sequencing Panel 81404 (x1), 81405 (x1), 81408 (x1) MM174 Limb Malformation: Deletion/Duplication Panel 81228 (x1) **CPT® is a registered trademark of the American Medical Association.

For more information about EGL and the nearly 1100 tests we offer: For more informationEMAIL about EGL GeneticsCALL and the nearly 1000WEB tests we offer: [email protected] 404-778-8499 www.geneticslab.emory.edu CALL WEB 470.378.2200 eglgenetics.com