Char syndrome, a familial form of patent ductus arteriosus, with a new finding: hyperplasia of the 3rd finger/Ailesel patent duktus arteriyozus: char sendromu ve yeni bir bulgusu; 3. parmak hipoplazisi.
Char syndrome is an autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and abnormalities of the fifth finger of the hand (1). The prevalence of Char syndrome has not been determined but is believed to be quite low.
This report describes a Turkish family including five individuals affected by this disorder with an R236C mutation in the gene encoding the neural-crest-related transcription factor AP-2b. Affected family members had the typical facial, hand and foot anomalies and additionally presented case has rarely reported polythelia and non reported hypoplasia of the 3rd finger.
A 15-day-old girl was referred because of a cardiac murmur. Consanguinity between the parents was denied. The respiratory and heart rates were 80/min and 160/min respectively, The patient had a flat midface, widely set eyes, mild ptosis, short philtrum and a triangular mouth; polythelia, foot and hand anomalies with clinodactyly were also noted (Fig. 1). Echocardiography revealed a large duct (6.5 mm) with unrestrictive ductal flow and predominantly left-to-right shunting, leading to left heart volume overload. The patient had an uneventful follow-up after surgical ligation and was discharged on the postnatal 45th day. The family history was suggestive for the presence of Char syndrome. His father, paternal uncle and a cousin were operated on for PDA. Similar phenotypic features and variable hand-foot anomalies were seen in them (Fig. 2). Additionally his paternal grandmother has typical facial dysmorphism, a small PDA, and polythelia. The pedigree is shown in Figure 1. Hypoplasia of the 3rd finger as a new finding in this syndrome was found in the proband and his father. Developmental, visual and hearing disorders were not detected in any members.
Genetic analysis of the TFAP2B coding exons and their flanking exons was performed as previously described (2). Analysis of the pro-band's genomic DNA revealed a coding region alteration in exon 4, a C-to-T transition at nucleotide 706 of the TFAP2B cDNA, which was present in heterozygosity. This sequence change predicted a substitution of an arginine by a cysteine at position 236. This change had not been previously identified in >340 control chromosomes. The R236C was also identified in the proband's affected father. Genetic analysis was not performed on other family members.
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
The incidence of isolated PDA in full-term infants is about 1 in 2,000 live births (3). However familial occurrence of PDA is quite rarely observed. Char syndrome has subsequently been reported by several investigators (4-7). No information is available concerning the likelihood of spontaneous closure of a PDA associated with Char syndrome, but it is likely to be rather low. Less common features associated with Char syndrome are polythelia, foot anomalies (interphalangeal joint fusion or clinodactyly, syndactyly), hearing abnormalities, visual impairment, development delay, parasomnia and other cardiac defects (4-6). Our proband had dysmorphic features, polythelia, foot and hand anomalies with clinodactyly and hypoplasia of the 3rd finger. Hypoplasia of the 3rd finger was found also in his father. This finding was not described previously in the literature to our best knowledge. Char syndrome was mapped to a narrow region of chromosome 6p12-p21 (8). Further studies showed that TFAP2B mutations cause Char syndrome (6). Zhao et al. (2) reported six TFAPB2 mutations that cause Char syndrome identified among 10 patients with the disorder and their families. An R236C mutation was detected in our propositus and his father. To the best of our knowledge, this is the first Turkish family in which Char syndrome has been detected.
The triad of Char syndrome has been variable in all families reported to date. The penetrance of Char syndrome has not been determined formally. One asymptomatic individual with a disease-causing TFAP2B mutation has been described (5). In our study, although the family members had all the characteristic features of this disorder, anomalies of hand/foot were variable. Moreover, the propositus and grandmother had polythelia. Zannoli et al. (7) first described polythelia as a feature of Char syndrome in 2000. We presented the second report of a family with Char syndrome exhibiting this feature. In the light of all these knowledge, we think that it can be described different features of this syndrome in the future.
Although rare, Char syndrome should be part of the differential diagnosis for patients with a family history of PDA, dysmorphic features, hand/foot anomalies and also polythelia. It is important to establish the diagnosis because the recurrence risk for the offspring was 50% in affected parents.
(1.) Char F Peculiar facies with short philtrum, duck-bill lips, ptosis and low-set ears-a new syndrome? Birth Defects Orig Artic Ser 1978; 14: 303-5.
(2.) Zhao F Weismann CG, Satoda M, Pierpont ME, Sweeney E, Thompson EM, et al. Novel TFAP2B mutations that cause Char syndrome provide a genoty-pe-phenotype correlation. Am J Hum Genet 2001; 69: 695-703. [CrossRef]
(3.) Moore P Brook MM, Heymann M. Patent ductus arteriosus and aortopulmo-nary window, In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF editors. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adults. 7th edition. Philadelphia, PA; Lippincott Williams & Wilkins: 2008. p.683-701.
(4.) Bertola DR, Kim CA, Sugayama SM, Utagawa CY, Albano LM, Gonzalez CH. Further delineation of Char syndrome. Pediatr Int 2000; 42: 85-8. [CrossRef]
(5.) Mani A, Radhakrishnan J, Farhi A, Carew KS, Warnes CA, Nelson-Williams C, et al. Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci USA 2005; 102: 2975-9. [CrossRef]
(6.) Satoda M, Zhao F, Diaz GA, Burn J, Goodship J, Davidson HR, et al. Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus. Nat Genet 2000; 25: 426. [CrossRef]
(7.) Zannolli R, Mostardini R, Matera M, Pucci L, Gelb BD, Morgese G. Char syndrome: an additional family with polythelia, a new finding. Am J Med Genet 2000; 95: 201-3. [CrossRef]
(8.) Satoda M, Pierpont ME, Diaz GA, Bornemeier RA, Gelb BD. Char syndrome, an inherited disorder with patent ductus arteriosus, maps to chromosome 6p12-p21.Circulation 1999; 99: 3036-42. [CrossRef]
Kadir Babaoglu, Meral Oruc *, Ayla Gunlemez *, Bruce D. Gelb 
Department of Pediatric Cardiology, and * Neonatology, Faculty of Medicine, Kocaeli University, Kocaeli-Turkey departments of Pediatrics and Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York-USA
Address for Correspondence/Yazisma Adresi: Dr. Kadir Babaoglu Kocaeli Universitesi Tip Fakultesi, Pediyatrik Kardiyoloji Bilim Dali, Kocaeli-Turkiye Phone: +90 262 303 80 35 Fax: +90 262 303 80 03 E-mail: email@example.com
Available Online Date/Cevrimici Yayin Tarihi: 22.06.2012
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Case Reports/Olgu Sunumlari|
|Author:||Babaoglu, Kadir; Oruc, Meral; Gunlemez, Ayla; Gelb, Bruce D.|
|Publication:||The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi)|
|Date:||Sep 1, 2012|
|Previous Article:||Conventional and computed tomography angiography views of a rare type of single coronary artery anomaly: right coronary artery arising from distal...|
|Next Article:||Fever, dyspnea and chest pain with pericardial effusion/ Ates, dispne, gogus agrisi ile birlikte perikard sivisi.|