Surgical Management of a Bowel Obstruction Secondary to a Volvulus in a Paediatric Patient with Bohring Opitz Syndrome

Mar Cotter^1*, Kristal Ylli¹, Shane Killeen¹

Cork University Hospital, Wilton, Cork, Republic of Ireland

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Abstract

Bohring Opitz syndrome (BOS) is a rare genetic disorder characterized by distinctive craniofacial features, a typical flexion posture, developmental delay, and multisystem involvement. Occurring as a result of a de novo pathogenic variant in the ASXL1 gene which disrupts chromatin remodelling and regulation of HOX gene expression. HOX gene expression is essential for normal embryological development. While feeding difficulties are a well-recognized and documented feature of BOS, their underlying mechanisms remain poorly understood. In this case report we describe a nine-year-old boy with genetically confirmed BOS who presented with a two history of progressive abdominal distension, vomiting, and inaudible bowel sounds. Imaging revealed high-grade obstruction, and emergent laparotomy demonstrated a colonic volvulus with ischemia affecting two thirds of the proximal colon. However most notably, the colon exhibited a complete absence of peritoneal fixation, allowing excessive mobility and predisposing to volvulus. Partial colectomy with ileocolic anastomosis and fixation of the remaining colon was performed, with excellent postoperative recovery.

This case highlights the potential aetiology of colonic non-fixation—an embryologic error linked to disrupted HOX gene regulation—as a contributing factor to the significant feeding intolerance commonly seen in BOS. Increased colonic mobility may impair intestinal transit and predispose to obstruction, compounding the neurogenic and motility-related issues previously hypothesised.

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Introduction

Bohring Opitz Syndrome (BOS) is a rare genetic disorder characterized by distinctive facial features, postural positining, growth retardation and varying levels of learning disabilities and was first described in the literature in 1999 by Axel Bohring and John M. Opitz.1 In 2011 it was determined that the condition is inherited in an autosomal dominant manner due to a de novo pathogenic variant in the ASXL1 gene². This gene provides instructions for protein synthesis that is involved in chromatin remodelling, which can alter how tightly DNA is packaged. The ASXL1 gene also regulates the expression of many other genes, including a group of genes known as HOX genes. HOX genes are involved in intrauterine growth and development. HOX genes, can in turn be switched on or off by ASXL1, depending on when they are needed. The ASXL1 gene is also one of the most frequently mutated genes in malignant myeloid diseases.  Prior to the identification of the molecular cause of Bohring Opitz syndrome (BOS), Hastings et al had outlined clinical diagnostic criteria for the condition³. The prevalence of BOS is unknown and is estimated to be 150-200 people worldwide, but his is widely variable. Russell et al, in their 2015 paper state that of the 46 people clinically diagnosed with Bohring Opitz syndrome, only 20 patients had a confirmed genetic mutation in the ASXL1 gene⁴. The following is a synopsis of the characteristics of BOS:

Facial Features:

• Micro/trigonocephaly
• Facial flammeus nevus
• Cleft lip/palate
• Micro/retrognathia

Growth and feeding complications:

• IUGR (Intrauterine growth restriction)
• Feeding difficulties from birth.

Neurologic complications:

• Moderate to severe learning disability
• Seizures

Respiratory issues:

• Recurrent infections

Sleep

• OSA (Obstructive sleep apnoea)

Ophthalmologic issues:

• High myopia presenting in infancy that may worsen over the first years of life
• Variable optic nerve and retinal anomalies

Characteristic Bohring Opitz posture:

• Elbow flexion
• Ulnar deviation
• Wrist flexion
• MCP (metacarpophalangeal) joint flexion
• Central hypotonia
• Limb hypertonia5

Case Description

A 9 year old male patient with a genetic diagnosis of BOS was brought to ED by his parents with a two day history of increasing abdominal distention, pain and generalised agitation. The patient had the characteristic features of BOS as mentioned previously. His medical and surgical history also included an atrial septal defect, not requiring surgical intervention, progressive early onset scoliosis with corrective surgery at four years of age and a left hip subluxation also managed conservatively. Due to his feeding intolerance he had a PEJ tube inserted in 2015. The parents, his full time carers reported that the child had not had a bowel motion in 2 days and had vomited 3 times. The patient was initially admitted under the care of paediatrics with a working diagnosis of constipation. On initial examination the abdomen was tense, but not rigid. However, on auscultation bowel sounds were inaudible. Plain film of the abdomen reported ‘dilated large bowel loops, 6.9 cm. Relatively collapsed descending colon. Appearances are concerning for high grade bowel obstruction’, as seen in Figure 1.

A surgical consult was immediately sought post PFA report. The abdomen was grossly distended, tympanic and tender to palpation and thus an urgent non contrast CT AP was recorded which subsequently reported long segment acute bowel ischaemia as seen in Figure 2.

The patient subsequently underwent an emergency laparotomy with partial colectomy with ilio-colic anastomosis. The entire colon was reduced from the abdominal cavity demonstrating a colonic volvulus around the middle colic vessels as seen in Figure 3 resulting in necrosis of approximately two thirds of the proximal colon, Figure 4. The most significant observation during the operation was that there was absolutely no peritoneal fixation of the colon. The volvulus was reduced. An ilio-colic anastomosis was undertaken via GIA 100 to the terminal ileum and descending colon ligature to mesentery. Side to side anastomosis with performed. Approximately 180cm of small bowel and 50 cm large bowel remained. The remaining descending colon was subsequently fixed to the lateral abdominal wall to prevent recurrence of rotation and subsequent volvulus. The patient was subsequently transferred to a paediatric unit once he was haemodynamically stable and discharged home well two weeks later and at one and three month follow ups.

Figure 1: Plain film of abdomen

Figure 2: Non contrast CT AP

Figure 3: Reduction of colon from abdominal cavity

Figure 4: Necrotic bowel

Discussion

The embryological development of the gastrointestinal system commences at week four and is focussed on elongation and rotation of the small bowel. Between weeks six and ten, organs derived from the midgut which include the colon are formed. Between weeks ten and twelve fixation of the mesentery of the colon to the parietal peritoneum occurs. Errors that occur during fixation can result in colonic non-fixation, internal hernias and volvulus⁶. HOX genes are noted to be involved in the regulation pathway of the GI system development in utero⁷. As stated earlier, the ASXL1 gene which is involved in the regulation of expression of HOX genes is mutated in BOS. Feeding issues begin at birth in children with BOS and include early satiety, chronic emesis, abdominal distension, and feeding-related discomfort, which can make sustaining adequate caloric intake difficult. Such issues have been hypothesised to occur secondary to severe gastroesophageal reflux however case reports to date have failed to produce diagnostic evidence of this and neither have they demonstrated any improvement on traditional pharmacological anti-reflux therapies. More recent publications have suggested a neurogenic aetiology resulting in delayed gastric motility⁸. In this case report non-fixation of the colon as discovered during the surgical intervention could potentially be a contributory causative agent in the feeding issues.  Non fixation of the colon in patients with BOS allows greater mobility of the colon potentially resulting in abnormal positioning with a resultant volvulus as in this case report. This potential positional instability may impede intestinal transit and may be a contributory aetiological factor in the significant feeding issues in individuals with BOS. Understanding the role of colon non-fixation helps guide clinicians toward earlier recognition and more effective intervention for feeding issues in BOS as well as highlighting the need for further clinical and molecular research into this potential contributory factor due to dysregulation of HOX gene expression secondary to ASXL1 mutation.

Conflict of Interest Statement:

No conflict of interest is reported for this case report.

Funding Statement:

No funding has been sought or received for this case report.

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