Adams-Oliver syndrome
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Adams-Oliver syndrome (AOS) is an extremely rare inherited disorder characterized by defects of the scalp and abnormalities of the fingers, toes, arms, and/or legs. The physical abnormalities associated with this disorder vary greatly among affected individuals. Some cases may be very mild while others may be severe. In infants with Adams-Oliver syndrome, scalp defects are present at birth and may include one or multiple hairless scarred areas that may have abnormally wide blood vessels directly under the affected skin. In severe cases, an underlying defect of the bones of the skull may also be present. In addition, infants with this disorder typically have malformations of the hands, arms, feet, and/or legs. These range from abnormally short fingers and toes to absent hands and/or lower legs. In some cases, additional abnormalities may also be present. Most cases of AOS appear to follow autosomal dominant inheritance but autosomal recessive inheritance has also been reported.

We provide testing for the genes listed below that are known to be associated with Adams-Oliver syndrome.

Type OMIM Gene/Protein Description
AOS1 100300 ARHGAP31/GAP

The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. ARHGAP31 mutations disrupt actin cytoskeletal structures, causing syndromic cutis aplasia and limb anomalies and the autosomal dominant form of Adams-Oliver syndrome.

AOS2 614219 DOCK6

Autosomal recessive multiple congenital anomaly syndrome that is characterized by aplasia cutis congenita and terminal transverse limb defects, in association with variable involvement of the brain, eyes, and cardiovascular systems.

AOS3 614814 RBPJ

Autosomal dominant form of Adams-Oliver syndrome involving characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects.

AOS4 615297 EOGT Autosomal recessive form characterized by cutis aplasia of the scalp, terminal transverse defects of the toes, and atrial septal defect.
AOS5 616028 NOTCH1 Caused by heterozygous mutation in the NOTCH1 gene on chromosome 9q34.defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects, in addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrently seen. Congenital heart defects have been estimated to be present in 20% of AOS patients.
AOS6 616589 DLL4

Caused by heterozygous mutation in the DLL4 gene on chromosome 15q15. Autosomal dominant disorder characterized by cutis aplasia and terminal transverse limb defects as well as congenital heart defects

Purpose:Confirmation of Clinical Diagnosis

Methodology: Next-Generation Sequencing

Test Requisition: Sequencing Requisition

Specimen Requirements: 2-5 mL Blood- Lavender Top Tube

Panel CPT Code: 81479 x 6 Cost: $3500.00 (Oklahoma Medicaid requires preauthorization for this test)

Provider can also select specific genes to be analyzed, this will affect pricing and CPT codes used for insurance filing.

Turn-around-time: 5-6 weeks

Shipping Information

References

1. Bandyopadhyay S, Chiang CY, Srivastava J, et al. (2010). "A human MAP kinase interactome". Nat. Methods 7 (10): 801–5.

2. Southgate L, et al. (2011). "Gain-of-Function Mutations of ARHGAP31, a Cdc42/Rac1 GTPase Regulator, Cause Syndromic Cutis Aplasia and Limb Anomalies". Am. J. Hum. Genet. 88 (5): 574–85.Shaheen, R., Faqeih, E., Sunker, A., Morsy, H., Al-Sheddi, T.,

3. Shamseldin, H. E., Adly, N., Hashem, M., Alkuraya, F. S. (2011) “Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome”. Am. J. Hum. Genet. 89: 328-333.

4. Hassed, S. J., Wiley, G. B., Wang, S., Lee, J.-Y., Li, S., Xu, W., Zhao, Z. J., Mulvihill, J. J., Robertson, J., Warner, J., Gaffney, P. M. (2012) “RBPJ mutations identified in two families affected by Adams-Oliver syndrome”. Am. J. Hum. Genet. 91: 391-395.

5. Shaheen, R., Aglan, M., Keppler-Noreuil, K., Faqeih, E., Ansari, S., Horton, K., et al. (2013) "Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams Oliver syndrome". Am. J. Hum. Genet. 92: 598-604.

6. Aguirre, A., Rubio, M.E., Gallo, V.(2010) "Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal". Nature 467:323-327.

7. Meester, J. A. N., Southgate, L., Stittrich, A.-B., Venselaar, H., et al..(2015) "Heterozygous loss-of-function mutations in DLL4 cause Adams-Oliver syndrome". Am. J. Hum. Genet. 97: 475-482.

8. Mu, W, et al."Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing". J Mol Diagn. 2016. 18(6):923-932.

 

 



Contact Information
Genetics Laboratory
University of Oklahoma Health Sciences Center
1122 NE 13 Street, Suite 1400, Oklahoma City, OK 73104
Phone: (405) 271-3589 |Fax: (405) 271-7117 Email: Dr. Shibo Li

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