Generalized, Partial and Atypical Lipodystrophy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
12603 ADRA2A 81479,81479 Order Options
AGPAT2 81479,81479
AKT2 81479,81479
ATP6V0A2 81479,81479
BANF1 81479,81479
BSCL2 81406,81479
CAV1 81479,81479
CAVIN1 81479,81479
CIDEC 81479,81479
FBN1 81408,81479
IGF1R 81479,81479
KCNJ6 81479,81479
LIPE 81479,81479
LMNA 81406,81479
LMNB2 81479,81479
MFN2 81406,81479
PCYT1A 81479,81479
PIK3R1 81479,81479
PLIN1 81479,81479
POLD1 81479,81479
PPARG 81479,81479
PSMA3 81479,81479
PSMB4 81479,81479
PSMB8 81479,81479
PSMB9 81479,81479
SPRTN 81479,81479
TBC1D4 81479,81479
WRN 81479,81479
ZMPSTE24 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
12603 Genes x (29) 81479 81406, 81408, 81479 $930 Order Options

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Lipodystrophies are a group of heterogeneous disorders characterized by loss of adipose (fat) tissue (Akinci et al. 2018. PubMed ID: 30406415). Lipodystrophy may be genetic or acquired. Broadly, the genetic lipodystrophies are classed as congenital generalized lipodystrophy (CGL), familial partial lipodystrophy (FPLD), or atypical and/or complex lipodystriophy, which may occur as a feature of progeroid syndromes (Akinci et al. 2018. PubMed ID: 30406415). Clinical features and severity vary depending of the type of lipodystrophy and the underlying genetic cause.

CGL is characterized by a near complete loss of adipose tissue at or soon-after birth and is typically accompanied by severe metabolic dysregulation (Patni and Garg. 2015. PubMed ID: 26239609; Akinci et al. 2018. PubMed ID: 30406415). Clinical features associated with CGL may include generalized lipodytrophy, a muscular appearance, prominent veins, accelerated growth, voracious appetite, umbilical hernias, hepatomegaly, splenomegaly, acanthosis nigricans, advanced bone age, and metabolic complications (insulin resistance, hypertriglyceridaemia, hepatic steatosis) (Patni and Garg. 2015. PubMed ID: 26239609; Akinci et al. 2018. PubMed ID: 30406415). The exact prevalence of CGL is unknown, but is estimated to be approximately 0.2 to 1 cases per million individuals (Chiquette et al. 2017. PubMed ID: 29066925).

FPLD is typically characterized by selective loss of adipose tissue, predominantly in the upper extremities, lower extremities, as well as the gluteal and pelvic regions (Ajluni et al. 2017. PubMed ID: 28199729; Lightbourne and Brown. 2017. PubMed ID: 28476236). The exact patterning and regional loss of adipose tissue is highly variable. Adipose tissue sparing and even accumulation may also be observed in the neck, trunk and abdomen of some affected individuals (Ajluni et al. 2017. PubMed ID: 28199729). Clinical features may also include non-alcoholic steatohepatitis, hypertriglyceridemia, insulin-resistant diabetes mellitus, proteinuria, microalbuminuria, hypertension, peripheral neuropathy, muscular dystrophy, myalgia, gallbladder disease, pancreatitis, as well as cardiovascular disease (Ajluni et al. 2017. PubMed ID: 28199729). Onset typically occurs anytime from late childhood through to adulthood. The exact prevalence of FPLD is unknown, but is estimated at approximately 3 cases per million individuals (Chiquette et al. 2017. PubMed ID: 29066925).

Atypical and/or complex lipodystropy may present with progeroid syndromes, cutis laxis, Keppen-Lubinsky syndrome, Ruijs-Aalfs syndrome, SHORT syndrome and CANDLE syndrome (Akinci et al. 2018. PubMed ID: 30406415). Clinical features for these syndromes may include a marfanoid or progeroid appearance, dermatological features, retinal features, and skeletal, cardiovascular and/or neurologic anomalies. Onset may occur at birth, soon-after birth, during childhood, or adolescence.

Medical management for lipodystrophy may include surveillance, psychological support, restriction of total fat intake, caloric restriction, increased physical activity, therapy for diabetes mellitus and hyperlipidemia, and possibly cosmetic surgery (Akinci et al. 2018. PubMed ID: 30370487). Genetic testing may aide in establishing a differential diagnosis, predicting the course of disease, and may assist reproductive planning.

Pathogenic variants in one or more of these genes included as part of this panel are reported to be associated with additional phenotypes including (but not limited to) progeroid syndromes, insulin resistance, severe obesity, skeletal dysplasia, neuropathy, muscular dystrophy, dermopathy, colorectal cancer, epilepsy susceptibility, and pulmonary hypertension.

Genetics

CGL is primarily inherited in an autosomal recessive manner (AGPAT2, BSCL2, CAV1, CAVIN1), however dominant inheritance is reported for atypical causes of CGL (FBN1, KCNJ6, LMNA, PPARG). FPLD may be inherited in an autosomal dominant (ADRA2A, AKT2, CAV1, LMNA, LMNB2, PLIN1, POLD1, PPARG, PSMA3, TBC1D4) or recessive manner (CIDEC, LIPE, PSMB4, PSMB8, PSMB9, ZMPSTE24). Atypical and/or complex lipodystropies are predominantly inherited in an autosomal recessive manner (BANF1, IGF1R, MFN2, PCYT1A, PIK3R1, SPRTN, WRN), although dominant inheritance is reported for the IGF1R, MFN2, and PSMA3 genes. Pathogenic variants may be inherited from a carrier parent, an affected parent, or arise de novo (Brehm et al. 2015. PubMed ID: 26524591; Lightbourne and Brown. 2017. PubMed ID: 28476236). The lipodystrophies are associated with small deletions, nonsense, splice site, frameshift, missense, and regulatory pathogenic variants. Structural variants, predominantly in the form of gross deletions, have been reported in isolated and familial cases of CGL (Agarwal et al. 2002. PubMed ID: 11967537; Purizaca-Rosillo et al. 2017. PubMed ID: 27868354). Structural variants, predominantly in the form of gross deletions, have also been reported in isolated cases of adult progeria Werner syndrome (Friedrich et al. 2010. PubMed ID: 20443122).

Although the function of some of the genes included in this panel are yet to be fully elucidated, several are known to be involved in phospholipid and triglyceride synthesis, the fusion of lipid droplets, adipogenesis, lipolysis, and biogenesis of caveolae (Holm et al. 1988. PubMed ID: 3420405; Peng et al. 2003. PubMed ID: 12782654; Evans et al. 2004. PubMed ID: 15057233; Capanni et al. 2005. PubMed ID: 15843404; Puri et al. 2007. PubMed ID: 17884815; Bosch et al. 2011. PubMed ID: 21497090; Patni and Garg. 2015. PubMed ID: 26239609).

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 98.8% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the genetic heterogeneity underlying the lipodystropies, the clinical sensitivity of this specific grouping of genes is difficult to estimate. However, it has been reported that up to 80% of individuals with CGL have an identifiable genetic cause (Akinci et al. 2018. PubMed ID: 30406415). Pathogenic variants in the LMNA and PPARG genes are estimated to account for more than 50% of all cases of FPLD (Jeru et al. 2017. PubMed ID: 27485410). Outside of these two genes, pathogenic variants explain only a small subset of FPLD cases. Presently, clinical sensitivity estimates for atypical and/or complex cases of lipodystrophy are unknown.

Indications for Test

Candidates for this test are patients with lipodystrophy, particularly cases with an atypical or complex etiology.

Diseases

Name Inheritance OMIM ID
Acquired Partial Lipodystrophy AD 608709
Acromicric Dysplasia AD 102370
Agammaglobulinemia 7, Autosomal Recessive AR 615214
Benign Scapuloperoneal Muscular Dystrophy With Cardiomyopathy AD 181350
Charcot-Marie-Tooth Disease Type 2B1 AR 605588
Charcot-Marie-Tooth disease, axonal, type 2A2B AR 617087
Charcot-Marie-Tooth Disease, Type 2A2 AD 609260
Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome AR 256040
Colorectal cancer, susceptibility to, 10 AD 612591
Congenital Generalized Lipodystrophy Type 1 AR 608594
Congenital Generalized Lipodystrophy Type 2 AR 269700
Cutis Laxa, Autosomal Recessive, Type IIA AR 219200
Diabetes Mellitus, Noninsulin-Dependent AD 125853
Dilated Cardiomyopathy 1A AD 115200
Distal Hereditary Motor Neuronopathy Type 5 AD 600794
Ectopia Lentis, Isolated, Autosomal Dominant AD 129600
Emery-Dreifuss muscular dystrophy 3, AR AR 616516
Encephalopathy, progressive, with or without lipodystrophy AR 615924
Epilepsy, Progressive Myoclonic, 9 AR 616540
Geleophysic Dysplasia 2 AD 614185
Heart-Hand Syndrome, Slovenian Type AD 610140
Hutchinson-Gilford Syndrome AR 176670
Hypoglycemia, Neonatal, Simulating Foetopathia Diabetica AD 240900
Immunodeficiency 36 AD 616005
Insulin-Like Growth Factor 1 Resistance To AR 270450
Keppen-Lubinsky syndrome AD 614098
Lipodystrophy, Congenital Generalized, Type 3 AR 612526
Lipodystrophy, Congenital Generalized, Type 4 AR 613327
Lipodystrophy, Familial Partial, Type 2 AD 151660
Lipodystrophy, Familial Partial, Type 3 AD 604367
Lipodystrophy, Familial Partial, Type 4 AD 613877
Lipodystrophy, familial partial, type 5 AR 615238
Lipodystrophy, familial partial, type 6 AR 615980
Malouf Syndrome AD 212112
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome AD 615381
Mandibuloacral Dysplasia With Type A Lipodystrophy AR 248370
Mandibuloacral Dysplasia With Type B Lipodystrophy AR 608612
Marfan lipodystrophy syndrome AD 616914
Marfan Syndrome AD 154700
Mass Syndrome AD 604308
Muscular Dystrophy, Congenital, LMNA-Related AD 613205
Nestor-Guillermo Progeria Syndrome AR 614008
Neuropathy, Hereditary Motor and Sensory, Type VIA AD 601152
Obesity AR 601665
Partial Lipodystrophy, Congenital Cataracts, and Neurodegeneration Syndrome AD 606721
Proteasome-associated autoinflammatory syndrome 3 and digenic forms AR 617591
Pulmonary hypertension, primary, 3 AD 615343
Restrictive Dermopathy, Lethal AR 275210
Ruijs-Aalfs syndrome AR 616200
SHORT syndrome AD 269880
Spastic Paraplegia 17 AD 270685
Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy AR 608940
Stiff Skin Syndrome AD 184900
Weill-Marchesani Syndrome 2 AD 608328
Werner Syndrome AR 277700
Wrinkly Skin Syndrome AR 278250
{Diabetes mellitus, noninsulin-dependent, 5} AR 616087

Related Tests

Name
PGxome®
CANDLE Syndrome via the PSMB8 Gene
Congenital Generalized Lipodystrophy (CGL) Panel
Lipodystrophy and Heritable Pulmonary Arterial Hypertension via the CAV1 Gene
Overgrowth and Macrocephaly Syndromes Panel

Citations

  • Agarwal et al. 2002. PubMed ID: 11967537
  • Ajluni et al. 2017. PubMed ID: 28199729
  • Akinci et al. 2018. PubMed ID: 30406415
  • Akinci et al. 2018. PubMed ID: 30370487
  • Bosch et al. 2011. PubMed ID: 21497090
  • Brehm et al. 2015. PubMed ID: 26524591
  • Capanni et al. 2005. PubMed ID: 15843404
  • Chiquette et al. 2017. PubMed ID: 29066925
  • Evans et al. 2004. PubMed ID: 15057233
  • Friedrich et al. 2010. PubMed ID: 20443122
  • Holm et al. 1988. PubMed ID: 3420405
  • Jéru et al. 2017. PubMed ID: 27485410
  • Lightbourne and Brown. 2017. PubMed ID: 28476236
  • Patni and Garg. 2015. PubMed ID: 26239609
  • Peng et al. 2003. PubMed ID: 12782654
  • Puri et al. 2007. PubMed ID: 17884815
  • Purizaca-Rosillo et al. 2017. PubMed ID: 27868354

Ordering/Specimens

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We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


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