|Year : 2016 | Volume
| Issue : 4 | Page : 193-195
Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome
Tuncer Ahmet Ali1, Karavelioglu Afra2, Baskin Embleton Didem2, Elmas Muhsin3
1 Department of Paediatric Surgery, Yuksekova State Hospital, Hakkari, Turkey
2 Department of Paediatric Surgery, Afyon Kocatepe University, Afyonkarahisar, Turkey
3 Department of Medical Genetic, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey
|Date of Web Publication||19-Jul-2016|
Tuncer Ahmet Ali
Department of Paediatric Surgery, Yuksekova State Hospital, Hakkari 30300
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder, characterized by upper limb dysplasia and congenital cardiac defect. We report two cases with HOS, first associated with renal agenesis, coronal hypospadias, urethral duplication and second associated with duodenal atresia and horseshoe kidney that have not been reported in English literature.
Keywords: Duodenal atresia, hand-heart syndrome, Holt-Oram syndrome, urogenital anomalies
|How to cite this article:|
Ali TA, Afra K, Didem BE, Muhsin E. Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome. J Indian Assoc Pediatr Surg 2016;21:193-5
|How to cite this URL:|
Ali TA, Afra K, Didem BE, Muhsin E. Coexisting urogenital anomaly and duodenal atresia in two atypical Holt-Oram syndrome. J Indian Assoc Pediatr Surg [serial online] 2016 [cited 2019 Sep 19];21:193-5. Available from: http://www.jiaps.com/text.asp?2016/21/4/193/186552
| Introduction|| |
Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder involving the hands, arms, and the heart anomalies.  Congenital cardiac and upper limb malformations often occur together and categorized as heart-hand syndromes. The most common of them is the HOS, which characterized by septal defects of the heart and preaxial radial ray abnormalities. The frequency is 1/100,000 live births.  Herein, two cases with HOS are reported, the first one associated with renal agenesis, coronal hypospadias, urethral duplication and the second one associated with duodenal atresia and horseshoe kidney.
| Case reports|| |
Written informed consents were obtained from the parents of the reviewed patients.
A 7-year-old boy was admitted to our clinic with complaints of swelling and pain in his right scrotum. Coronal hypospadias, left simple ear, aplasia of right thumb, and radius was seen in physical examination in addition to erythema and edema of the right scrotum [Figure 1]. It was learned that he had an operation for atrial septal defect (ASD) 2 years ago. Ultrasound revealed the left kidney agenesis. After antibiotic treatment for epididymitis, an operation was planned for coronal hypospadias. Physical examination under anesthesia revealed type-1 incomplete urethral duplication according to Effmann classification.  Hypospadias repair was performed using the urethra extending into the bladder with "Eccentric circummeatal-based (ECMB) flap" technique and the blind ending urethra was excised. The patient is doing well for 18 months after surgery.
|Figure 1: Operation scar on chest wall due to atrial septal defect repair (asterix), simple left ear (arrowhead), and right thumb and radial aplasia (arrow) are shown|
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A full-term, 3-day-old girl was admitted to the emergency department with the lack of oral intake. Syndromic facial appearance, phocomelia in the bilateral upper extremities, and hypertrichosis in the left ear and left lower leg were detected in physical examination [Figure 2]. Abdominal X-ray revealed double bubble sign, ultrasound demonstrated horseshoe kidney, and echocardiography showed a ventricular septal defect (VSD). Diamond-shaped duodenoduodenostomy was performed and the patient is being followed up without any complication for 20 months.
|Figure 2: Phocomelia (radial aplasia) of bilateral upper extremities (arrows)|
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| Discussion|| |
HOS was first described by Holt and Oram in 1960.  Although family history presents in 60-70% of the cases and de novo mutations are present in 30-40% of the cases. Mutations in 12q24.1 band located in TBX5 gene that has a key role in embryonic development constitute the typical HOS phenotype. , However, sporadic cases have also been reported.  Upper limb abnormalities, such as phocomelia and minor thumb anomalies are also observed in all patients. In 50-95% of patients ostium secundum type ASD, VSD, patent ductus arteriosus, heart block, and disorders such as Wolff-Parkinson-White syndrome are observed. , Thus, this syndrome also called hand-heart syndrome.
The differential diagnosis should be done from SALL-4 related disorders, ulnar-mammary syndrome, VACTERL/VATER association, and Townes-Brocks syndrome because all of them have the same skeletal anomalies with HOS. In addition to this, coloboma and Duane anomaly in the eyes seen in SALL-4 related disorders, hypogonadism seen in ulnar-mammary syndrome, vertebral, trachea-esophageal, and anal anomalies seen in VACTERL/VATER association ear and anal anomalies seen in Townes-Brocks syndrome. ,, Therefore, none of these anomalies was seen in our patients, these syndromes are eliminated.
HOS was diagnosed clinically owing to heart and upper limb anomalies in both cases. To best of our knowledge, association with renal agenesis, type-1 incomplete urethral duplication and hypospadias that seen in first case and association with duodenal atresia that seen in second case has not been reported in English literature before, although some unusual associated anomalies have been described in HOS such as craniofacial, tracheal, pulmonary, vertebral, renal, lower limb anomalies, cleft uvula, brain cyst, spleen anomaly, pyelon duplex, ectopic kidney, and hemivertebra. 
TBX5 mutation was detected only in 74% of HOS affected individuals.  There were no TBX5 gene mutations in both of the cases.
The combination of hypospadias and urethral duplication is very rare encountered in the literature. ECMB flap technique that was preferred to repair hypospadias facilitated to recognition, and excision of urethral duplication. Cardiological evaluation should be done in patients with HOS before surgery if required for any reason.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]