Patients with anorectal malformation and upper limb anomalies: genetic evaluation is warranted.
The objective of this study was to compare the prevalence of genetic disorders in anorectal malformation (ARM) patients with upper limb anomalies to that in ARM patients with other associated anomalies. A retrospective case study was performed in two pediatric surgery centers. All patients born between 1990 and 2012 were included. VACTERL (vertebral defects (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula with esophageal atresia (TE), renal dysplasia (R), and limb anomalies (L)) was defined as at least three components present. We included 700 ARM patients: 219 patients (31 %) had isolated ARM, 43 patients (6 %) had a major upper limb anomaly, and 438 patients (63 %) had other associated anomalies. The most prevalent upper limb anomalies were radial dysplasia (n = 12) and hypoplastic thumb (n = 11). Ten of the 43 patients (23 %) with an upper limb anomaly were diagnosed with a genetic disorder-nine also met the VACTERL criteria-vs. 9 % of ARM patients with other anomalies (p = 0.004, chi-squared test).


CONCLUSIONS
Genetic disorders are twice as frequently diagnosed in ARM patients with upper limb anomalies than in those with other anomalies. As they also frequently meet the VACTERL criteria, it is important to consider VACTERL as a diagnosis per exclusionem. Genetic counseling is certainly warranted in these patients.


BACKGROUND
• Anorectal malformations (ARMs) often co-occur with other congenital anomalies, including upper limb anomalies, mainly of pre-axial origin. • Co-occurrence of ARMs and upper limb anomalies is seen in disorders such as Townes-Brocks syndrome, Fanconi anemia, and VACTERL association. What is New: • ARM patients with a major upper limb anomaly-with or without other congenital anomalies-have a twofold greater chance of a genetic disorder than have non-isolated ARM patients without upper limb anomalies. • Not all upper limb anomalies in ARM patients are part of the VACTERL association; a workup for genetic evaluation is proposed.
Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room SK-1280, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
Desiree
D
van den Hondel
Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
Charlotte H W
CH
Wijers
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Yolande
Y
van Bever
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Annelies
A
de Klein
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Carlo L M
CL
Marcelis
Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room SK-1280, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.|Department of Surgery-Pediatric Surgery, Amalia Children's Hospital, Radboudumc, Nijmegen, The Netherlands.
Ivo
I
de Blaauw
Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room SK-1280, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
Cornelius E J
CE
Sloots
Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Room SK-1280, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands. h.ijsselstijn@erasmusmc.nl.
Hanneke
H
IJsselstijn
D001003:Anal Canal / Q000002:abnormalities*; D000071056:Anorectal Malformations / Q000453:epidemiology* / Q000235:genetics; D004947:Esophagus / Q000002:abnormalities*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000453:epidemiology*; D006330:Heart Defects, Congenital / Q000453:epidemiology*; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D017880:Limb Deformities, Congenital / Q000453:epidemiology*; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D013131:Spine / Q000002:abnormalities*; D014132:Trachea / Q000002:abnormalities*; D038062:Upper Extremity Deformities, Congenital / Q000453:epidemiology* / Q000235:genetics
Anorectal atresia; Anorectal malformation; Syndrome; Upper extremity deformities, congenital; VACTERL association