Comprehensive EDS Panel

Posted on by Dru Leistritz

The Collagen Diagnostic Laboratory specializes in testing for Ehlers-Danlos Syndrome and offers the most comprehensive EDS testing available. The Comprehensive EDS Panel includes testing for 15 genes associated with Ehlers-Danlos Syndrome, including the recently described Periodontal form of EDS (EDS type VIII).   Panel genes: COL5A1, COL5A2, COL3A1, FLNA, PLOD1, COL1A1, COL1A2, ADAMTS2, C1S, C1R, ATP7A, CHST14, FKPB14, SLC39A13, and AEBP1.

COMPREHENSIVE EDS PANEL

CLASSIFICATIONCLINICAL FEATURESINHERITANCEGENE(S)AVAILABLE CLINICAL TESTING
Classical Type (EDS types I)Soft, velvety, hyperextensible skin; easy bruising; "cigarette paper" scarsDominantCOL5A1 and COL5A2Classical EDS
EDS Panel
Comprehensive EDS Panel
Classical type (EDS type II)Similar to EDS type I but less severe. Soft, hyperextensible skin; joint hypermobility; bruising; normal scar formationDominant (rare recessives)COL5A1 and COL5A2Classical EDS
Classical-like, 2 Joint and skin laxity, osteoporosis, osteoarthritis, abnormal scarring, joint dislocationsRecessiveAEBP1Comprehensive EDS Panel
Hypermobility Type (EDS type III) or Tenascin Deficient TypeMarked large and small joint hypermobility, joint pain, easy bruising, easy bleeding, normal scarsDominantTNXB (<5%)(Not available through CDL)
Vascular Type (EDS type IV)Thin, translucent skin with visible veins; marked bruising; skin and joints have normal extensibility; arterial, bowel and uterine ruptureDominantCOL3A1Vascular, type IV
Ocular-scoliotic (Kyphoscoliosis) Type (EDS type VI)Progressive kyphoscoliosis, joint hypermobility, smooth, hyperelastic and fragile skin, muscular hypotonia and scleral fragility and rupture of the globeRecessivePLOD1Ocular-scoliotic, type VI
Arthrochalasia Type (EDS type VIIA and VIIB)Congenital hip dislocation; very soft, fragile, bruisable skin, marked joint hypermobility, blue sclerae, small jaw, hypertrichosisDominantCOL1A1, COL1A2Arthrochalasia, type VII A/B (Exon 6 COL1A1/2 )
Dermatosparaxis Type (EDS type VIIC)Soft and very thin, fragile skin (tearing of the skin), stretchy skin, easy bruising, joint hypermobilityRecessiveADAMTS2Dermatosparaxis, Type VIIC
Cardiac-Valvular FormJoint hypermobility, skin hyperextensibility, cardiac valvular defectsRecessiveCOL1A2Comprehensive EDS Panel
Periodontal (EDS type VIII)Periodontitis, gingival recession, early tooth loss, easy bruising, skin hyperpigmentation, atrophic scars, joint hypermobility, thin skinDominantC1S, C1RPeridontal, Type VIII
Musculocontractural TypeCraniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, hypotonia, thin skin, easy bruising, atrophic scarring, joint hypermobilityRecessiveCHST14Comprehensive EDS Panel
EDS with progressive kyphoscoliosis, myopathy, and hearing lossSevere muscle hypotonia at birth, progressive scoliosis, joint hypermobility, elastic skin, myopathy, hearing lossRecessiveFKBP14FKBP14-Related EDS
Occipital horn (EDS type XI)Easy bruising, hyperelastic skin, hernias, bladder diverticula, joint hypermobility, varicosities, multiple skeletal abnormalitiesX-Linked RecessiveATP7AComprehensive EDS Panel
Periventricular heterotopia variant (PVNH4)Epilepsy, cardiac defects, joint hypermobilityX-Linked DominantFLNAComprehensive EDS Panel
Spondylocheirdysplastic formShort stature, blue sclerae, thin and hyperelastic skin, muscle atrophyRecessiveSLC39A13Comprehensive EDS Panel

Please consult the Ehlers-Danlos Syndrome Test Guide for more information.

OI and Genetic Bone Disorders Panel

Posted on by Dru Leistritz

The Collagen Diagnostic Laboratory offers a comprehensive Osteogenesis Imperfecta (OI) and Genetic Bone Disorder panel of 42 genes.  The OI and Genetic Bone Disorders panel includes 4 genes associated with autosomal dominant forms of OI, COL1A1, COL1A2, IFITM5 and PLS3, and 13 genes associated with autosomal recessive forms of OI and hypophosphatasia, FKBP10, CRTAP, P3H1/LEPRE1, PPIB, SERPINH1, SP7/OSX, SERPINF1, PLOD2, ALPL, BMP1, TMEM38B, WNT1 and CREB3L1.  It also includes testing for hypophosphatasia, x-linked osteoporosis, bone mineralization disorders, and other skeletal dysplasias (see complete list on test requisition form).

This panel may be done in a tiered manner, with the dominant genes tested first and the remaining genes only tested if the dominant genes were normal (please indicate this on the test requisition form).  Over 95% of OI phenotypes result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen, so this test is always recommended as a first step in testing individuals with a clinical diagnosis of OI.

When considering recessive forms of OI or other bone disorders, consultation with the laboratory genetic counselors or laboratory director is recommended as clinical and family history and x-ray review may be needed.  Occasionally new candidate genes for recessive form of OI will be included as part of the panel; there is no additional charge for testing of these genes.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

Comprehensive Dominant OI Panel

Posted on by Melanie Pepin

PLEASE NOTE:  As of August 1, 2017 this panel has been replaced by the OI and Genetic Bone Disorders Panel.  Please contact the laboratory (206-543-5464) to special order.

The Comprehensive Dominant OI Panel offers sequencing for non-recessive forms of OI. Causative mutations have been identified in several genes associated with autosomal dominant forms of Osteogenesis Imperfecta (OI):  most commonly in COL1A1, COL1A2 and IFITM5 but also in P4HB, LRP5, ALPL and WNT1.  Recently, mutations in a single gene associated with X-linked OI, PLS3, have been identified.

Over 95% of OI phenotypes result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the a1 or a2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, fracture frequency, stature and deformity.

OI type V is also a dominant form of OI resulting from a mutation in IFITM5, the gene that encodes interferon induced transmembrane protein 5.  Type V has a wide range of presentation but with distinguishing clinical and radiological features that can include a propensity to hyperplastic callus formation, calcification of the forearm interosseous membrane, radiodense metaphyseal bands, and radial head dislocation.

Hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

Autosomal Dominant OI Panel

Posted on by Melanie Pepin

Causative mutations have been identified in three genes associated with autosomal dominant forms of Osteogenesis Imperfecta (OI):  COL1A1, COL1A2 and IFITM5.

 Over 95% of OI phenotypes result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the a1 or a2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, fracture frequency, stature and deformity.

OI type V is also a dominant form of OI resulting from a mutation in IFITM5, the gene that encodes interferon induced transmembrane protein 5.  Type V has a wide range of presentation but with distinguishing clinical and radiological features that can include a propensity to hyperplastic callus formation, calcification of the forearm interosseous membrane, radiodense metaphyseal bands, and radial head dislocation.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

COL1A1 and COL1A2 gDNA Testing

Posted on by Melanie Pepin

Over 95% of the forms of OI (lethal and non-lethal) result from a single dominant mutation in either COL1A1 or COL1A2, the two genes that encode the chains of type I procollagen.  The phenotype that results from the disease-causing variant is a consequence of the underlying mutation type and location in the alpha 1 or alpha 2 chain of type I procollagen.  Null mutations of COL1A1 result in OI type I and missense mutations in either COL1A1 or COL1A2 result in variable phenotypes within a spectrum of age of onset, stature and deformity.

For guidelines on the correct test to order and for pertinent references, consult the Osteogenesis Imperfecta Test Guide.

EDS type VII Testing

Posted on by Stephen Schildbach

EDS type VII, the Arthrochalasia type, is characterized by congenital hip dislocation, joint hypermobility, soft skin with normal scarring, easy bruising, blue sclerae, small jaw, and hypertrichosis.  It is typically identified in infancy.