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2014-02-01-11 Case of the week #366 © Cuillier www.TheFetus.net 

 
Answer to the case of the week #366

April 03, 2014 - April 17, 2014

Fabrice Cuillier, MD1; D. Mardamootoo, MD1; J. L. Alessandr, MD2.

1. Department of Gynecology, Félix Guyon CHU, 97400 Saint-Denis, Réunion Island, France; 
2. Department of Neonatology, Félix Guyon CHU, 97400 Saint-Denis, Réunion Island, France.
 

Case report

A 22-year-old woman (G1P0), was referred to our department at 24 weeks of gestation. Some members of her family had hexadactyly of the hands and the feet. She was also born with suspicion of an autosomal dominant syndrome with polydactyly and bifid thumb and underwent surgical correction.

Her ultrasound examination at 12 weeks was reported to be normal (NT 1 mm, CRL 58 mm) and so was the triple test.

Another ultrasonographic examination was done at 24 weeks and revealed following findings:

Macrocrania with mild hypertelorism and flat fetal profile;
- Postaxial polydactyly of the hands (6 fingers);
- "Sandal gaps" with broad toes and polydactyly;
- Normal fetal biometry concordant with expected gestational age and normal amniotic fluid volume.

The patient had refused amniocentesis. 
The newborn was delivered at 38 weeks by cesarean section (female; 4100 g). Neonatal examination showed postaxial polydactyly of hands, preaxial polydactyly of the feet with broad thumbs and partial syndactyly of the first and second digits.

Final genetic diagnosis was done by a comparative genomic hybridization micro (CGH) array, showing deletion and disruption of GLI3 (46 XX) corresponding to
 Greig cephalopolysyndactyly (GCPS) syndrome.

Images 1, 2, 3: The images show slightly prominent forehead with flattened fetal profile and mild hypertelorism.

 

 

Images 4-13: The images show 2D and 3D scans of the fetal hands with postaxial polydactyly.

 

 

 

 


 

Images 15-23, video 1: The images and video shows preaxial polydactyly of the feet with broad thumb and partial syndactyly of the first and second digits.

 


 

 


 

 


 

Image 24: Fetal biometry - macrocephaly and just mild hypertelorism were present.




Images 25-33: Postnatal images of the newborn with 
Greig cephalopolysyndactyly syndrome: macrocephaly, prominent forehead, postaxial polydactyly of the hands, preaxial polydactyly of the feet with partial syndactyly of the first and second digits.

 

 




 

 

Synonyms

Greig cephalopolysyndactyly (GCPS) syndrome.
Greig syndrome.
Greig cephalo-syndactyly syndrome.

Definition
 
Greig cephalo-polysyndactyly syndrome (GCPS) is a disorder that affects development of the limbs, head and face. The GCPS is a rare, pleiotropic, multiple congenital anomaly syndrome and is characterized by the primary clinical triad of polysyndactyly, macrocephaly and hypertelorism. Macrocephaly, hypertelorism, frontal bossing and polydactyly vary a lot in appearance and severity.

People with this condition typically have extra fingers or toes or an abnormally wide thumb (or double thumbs) or big toe (hallux). Polydactyly can be preaxial or postaxial, and may involve the hands and feet. The skin between the fingers and toes may be fused (cutaneous syndactyly).

This disorder is also characterized by an abnormally large head size (macrocephaly) and a high, prominent forehead, without brain anomaly and classically, but not usually, by widely spaced eyes (ocular hypertelorism). In the most severe form of spectrum, mental retardation, hydrocephaly and brain seizures were also described, rarely.

The eponym was coined to credit the clinical descriptions of David Greig, a surgeon from Edinburg (1926). Initially, the term Greig syndrome was used to described macrocephaly with hypertelorism.

Prevalence

Exact prevalence is unknown. Biesecker estimates that it is 1 to 9 : 1 000 000.

Etiology
 
Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome

Pathogenesis
 
Hereditary GCPS is inherited in an autosomal dominant manner. Individuals with the syndrome may have an affected parent. The syndrome may also occur as a de novo gene mutation.

Sonographic findings
 
Primary clinical triad in GCPS consists of polysyndactyly, macrocephaly with frontal bossing and hypertelorism. The limbs anomalies of GCPS are markedly variable. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. 

The cranio-facial manifestations are also highly variable. Some patients have significant hypertelorism (with increased inter-pupillary distance) with or without telecanthus (increased inner canthal distance). Some patients also have macrocephaly, which is not typically associated with central nervous system (CNS) anomalies. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment. 

Differential diagnosis
 
Acro-callosal syndrome

Acrocallosal syndrome is GCPS contiguous gene syndrome. GCPS is allelic to the Pallister-Hall syndrome and one form of the acro-callosal syndrome. Preaxial and postaxial polydactyly, syndactyly, agenesis of the corpus callosus (exceptional in GCPS), hypertelorism, macrocephaly, mental retardation with seizures, and umbilical and inguinal hernias are classical features and differentiate the acro-callosal syndrome from GCPS.

Oro-facial-digital syndrome

Facial features include a cleft lip, a wide nose with abroad, flat nasal bridge and hypertelorism. Abnormalities of the digits include syndactyly and brachydactyly, clinodactyly. Polydactyly is rare.

Carpenter syndrome

Carpenter syndrome belongs to acro-cephalo-polysyndactyly disorders, and presents with craniosynostosis.

Postaxial or preaxial polydactyly type A syndrome and preaxial polydactyly type 4

No macrocephaly or hypertelorism is present in these cases.

Prognosis

Rarely, the affected individuals may have more serious medical problems including seizures, developmental delay, and intellectual disability. In most cases the prognosis is good. Patients with large deletions that include GLI3 may have a worse prognosis.

Recurrence risk
 
GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern.

Management
 
Treatment is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations.
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