[Clinical and molecular characteristics of a child with familial adenomatous polyposis]
Juan Zhang1, Zailing Li, Xuebiao Huang
1Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China.
Insights
This study details a child with early-onset familial adenomatous polyposis (FAP), highlighting disease progression and a novel APC gene mutation. Sulindac showed partial effectiveness in managing polyps, suggesting a potential sporadic case.
Area of Science:
- Genetics
- Pediatric Gastroenterology
- Molecular Biology
Background:
- Familial adenomatous polyposis (FAP) is a genetic disorder characterized by numerous colorectal polyps.
- Early-onset FAP in childhood presents unique clinical challenges and requires long-term management strategies.
Observation:
- A 6-year-old girl presented with early-onset FAP, exhibiting rapid polyp development and progression over 11 years.
- Colonoscopy revealed extensive polyposis in the colon and rectum, with additional polyps in the gastric fundus and body.
- Genetic analysis identified a novel 5 bp deletion (c.3927_3931delAAAGA) in the APC gene, inconsistent with parental genetic profiles.
Findings:
- The patient's FAP demonstrated clinical exacerbation with age, despite partial polyp control with sulindac treatment.
- The identified APC gene mutation suggests a possible sporadic occurrence of FAP in this pediatric case.
- No evidence of carcinoma was found in biopsies, even with high-grade dysplasia present.
Implications:
- This case underscores the importance of genetic mutation analysis in diagnosing early-onset FAP, especially in the absence of a family history.
- The findings contribute to understanding the genotype-phenotype correlation in FAP and the potential role of sporadic mutations.
- Long-term surveillance and therapeutic interventions like sulindac may help manage FAP progression in pediatric patients, potentially delaying or avoiding surgery.
Objective:
To explore the clinical features and molecular mutation of early-onset familial adenomatous polyposis(FAP) in childhood.
Method:
The clinical features, endoscopic findings, pathology and therapeutic effect of sulindac during 11 years follow-up in a child with FAP were retrospectively reviewed . Adenomatous polyposis coli (APC) gene mutation analysis was performed by PCR and first generation sequencing.
Result:
This 6-year-old girl was admitted for intermittent bloody stool during the last one and a half years. Colonoscopy showed hundreds of polyps in the rectum and colon. Pathological examination revealed tubular adenomas with high grade dysplasia. During the follow-up period of 11 years, the child presented intermittent mucous bloody stool. Endoscopy showed the number of polyps in colon and rectum increased to thousands, and found multiple polyps in gastric fundus and body.She was treated with sulindac at the age of 13. Then the number of polyps and the grade of pathology showed a slight improvement and no carcinoma was seen on biopsy. She has not accepted surgery until now. Gene sequencing of this child revealed 5 bp deletion at codon 1,309 of exon 15 (c.3927_3931delAAAGA) of tumor suppressor gene, whereas none of her parents had the same mutation. And no polyps were found on her parents colonoscopy.
Conclusion:
This child with FAP had an early onset of this disease, and clinical conditions were exacerbated with age. Sulindac was partially effective in controlling size and number of polyps. The site of mutation in this case was consistent with classic FAP, and without family history, the mutation may be a sporadic one.
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