J Korean Med Sci.  2007 Apr;22(2):352-356. 10.3346/jkms.2007.22.2.352.

The First Korean Case of Beare-Stevenson Syndrome with a Tyr375Cys Mutation in the Fibroblast Growth Factor Receptor 2 Gene

• Eun SH
• Ha KS
• Je BK
• Lee ES
• Choi BM
• Lee JH
• Eun BL
• Yoo KH

• KMID: 1713200
• DOI: http://doi.org/10.3346/jkms.2007.22.2.352

Abstract

Here we report the first case of a Korean infant with a cloverleaf-shaped craniosynostosis, in which the diagnosis of Beare-Stevenson syndrome was suspected upon observation of the typical morphological features. This infant exhibited craniofacial anomalies, ocular proptosis, cutis gyrata, acanthosis nigricans, prominent umbilical stump, furrowed palms and soles, hypospadia, and sacral skin tag coupled with dermal sinus tract. Brain magnetic resonance imaging revealed that the patient also had non-communicating hydrocephalus with Chiari malformation. This is the 8th report of Beare-Stevenson syndrome in the literature, which was confirmed by the detection of a Tyr375Cys mutation in the fibroblast growth factor receptor 2 (FGFR2) gene.

Keyword

Craniosynostosis; Beare-Stevenson Syndrome; Mutation; FGFR2 Gene

MeSH Terms

Syndrome
Receptor, Fibroblast Growth Factor, Type 2/*genetics
Polymorphism, Single Nucleotide/genetics
Mutation
Male
Korea
Infant, Newborn
Humans
Genetic Predisposition to Disease/genetics
DNA Mutational Analysis
Craniosynostoses/diagnosis/*genetics
Craniofacial Abnormalities/diagnosis/genetics
Abnormalities, Multiple/diagnosis/*genetics

Figure

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  Fig. 1 Photographs of the patient. (A) Craniofacial anomalies with severe ocular proptosis and depressed nasal bridge. (B) Hypospadia of penis but two normal testicles. (C) Sacral skin tag with sinus tract. (D) Cutis gyrate in deeply furrowed right palm. (E) Cutis gyrate in deeply furrowed right sole. (F) Cutis gyrate in right preauricular furrows.

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  Fig. 2 Skull AP view showed typical "cloverleaf" skull with severe temporal bulging (white short arrows), lacunar skull (black arrow), poorly developed maxillary bone, and significantly low-set ears with angulated posteriorly (white long arrows).

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  Fig. 3 (A) The contrast-enhanced T1-weighted midsagittal image revealed brachycephaly and the findings consistent with Chiari malformation, including shallow posterior fossa, the herniated tonsil, caudally displaced medulla, elongated 4th ventricle, and resultant obstructive hydrocephalus. (B) The left parasagittal image depicted exophthalmos. (C) Contrast-enhanced T1-weighted coronal image showed schizencephaly in the right middle cranial fossa. T1-weighted (D), T2-weighted (E), and FLAIR (F) axial images also show schizencephaly in the right middle cranial fossa, and dilated lateral and third ventricles.

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  Fig. 4 DNA sequencing revealed heterozygous mutation (A to G) in this infant. This mutation resulted in the amino acid substitution of cysteine (TGC) for tyrosine (TAC) at coden 375 (Tyr375Cys) of the fibroblast growth factor receptor 2 (FGFR2) gene.

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