Icahn School of Medicine at Mount Sinai
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Genetic Testing Lab

Test Catalog Molecular Genetics Laboratory Craniosynostosis Testing Panel

Craniosynostosis Testing Panel

Test Description:
Craniosynostosis is the early fusion of bones or premature ossification of sutures (the tissues between bones) of the skull. This developmental anomaly often leads to an abnormal head shape. It is common and occurs in approximately 1 per 2500 live births. There is considerable variability in physical appearance between patients with craniosynostosis. A common finding is brachycephaly (a shortened distance between the front and back of the head) due to early closure of one or both coronal sutures. Other sutures can be involved as well, and the most dramatic appearance would be that of a cloverleaf (kleeblattschadel) skull deformity when multiple sutures are affected. Some individuals have isolated craniosynostosis and are mildly affected with only abnormal head shape. Others are clinically diagnosed with one of the more than 100 inherited conditions with craniosynostosis as a feature. Among those with coronal synostosis is Crouzon syndrome which is associated with only craniofacial abnormalities. One major feature is prominent eyes or ocular proptosis. Other findings include flat midface, prominent mandible, strabismus, dental abnormalities, cleft palate, hearing loss, and cervical spine problems. Jackson-Weiss syndrome also has large great toes or other bony foot deformities. Pfeiffer syndrome has hand and feet abnormalities with broad thumbs and great toes, brachydactyly (short phalanges) and syndactyly (webbing), and more severe cases have upper arm (radioulnar) synostosis and other organ system abnormalities. Muenke syndrome is highly variable and can have features of the previously described disorders and carpal and tarsal bony fusion. Antley-Bixler-like syndrome resembles severe cases of Pfeiffer syndrome with bowing of femoral bones, fractures, and Antley-Bixler syndrome (POR syndrome) has ambiguous genitalia. Apert syndrome has severe craniofacial features, symmetric hand and feet syndactyly, and more than half have learning problems. Crouzonodermoskeletal and Beare-Stevenson syndromes are associated with dermatologic findings of acanthosis nigricans; the former also has choanal atresia and hydrocephalus, and the latter has cutis gyrata. Saethre-Chotzen syndrome presents with facial asymmetry, eyelid ptosis (drooping), and mild hand and foot brachydactyly and syndactyly. Baller-Gerold syndrome has radial ray defects and visceral organ abnormalities. Craniosynostosis, Boston type is associated with forehead retrusion, recession of the superorbital region and digital abnormalities. Craniofrontonasal dysplasia is distinct with midline problems including hypertelorism and broad nasal tip. Carpenter syndrome is associated with polydacyty (extra digits). All but two of these syndromes mentioned above display autosomal dominant inheritance; however a significant percentage of mutations are de novo. Antley-Bixler and Carpenter syndromes are the exceptions and are autosomal recessive conditions. Testing can be ordered for the entire panel or for select disorders. It is performed via DNA sequencing of the appropriate exon(s) (see table below). For three syndromes (CFNS, CRS2 and SCS), deletions or duplications of the target genes are also determined by MLPA. See detection rates in table below. This testing may be ordered for confirmation of a clinical diagnosis, to facilitate genetic counseling of an affected individual or family member, or for prenatal diagnosis.

1. Exon numbering according to ENSEMBL database
(www.ensembl.org/Homo_sapiens/index.html)
* If preceding exons are negative for any mutations, then the following exon(s) will be sequenced.

Specimen Requirements:
Two 5-10 ml tubes of anticoagulated blood. The preferred anticoagulant is EDTA (lavendar top tubes), ACD (yellow top) tubes are also accepted.

Shipping: Send at room temperature.

Turnaround Time: 3-4 weeks

CPT Codes:

Consent Form: Craniosynostosis Consent

Requisition Form: General Test Requisition