Peutz-Jeghers syndrome: early clinical expression of a new STK11 gene variant

Abstract

Genetic heterogeneity has been recognised in Peutz-Jeghers syndrome (PJS) (over 230 STK11 gene mutations reported). We report a rare PJS phenotype with early extensive gastrointestinal (GI) presentation and a new genetic variant. The case presented as haematochezia and mucocutaneous pigmentation (the patient was 3 years of age). Endoscopy showed several polyps throughout the stomach/colon (PJ-type hamartomas); the larger polyps were resected. Small bowel imaging detected multiple jejunum/ileum small polyps. During 8 years of follow-up of this asymptomatic patient, an increasing number of diffusely distributed polyps was observed and polypectomies were performed. Subsequently, the patient failed consultations; when the patient was 13 years of age, emergency surgery was required due to small bowel intussusception (ileal polyp). A STK11 gene study identified two missense variants in heterozygous (yet unknown significance but probably pathogenic): c.854T>A (exon 6) and c.446C>T* (exon 2) (*not previously reported). We report two STK11 gene variants (one not previously described) of yet undetermined causality in a paediatric patient presenting with extensive GI involvement at a very early age, with no family medical history. Structural and functional repercussion of the newly described variants should be further investigated.

Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome

“…A total of 10 variations were found, primarily in exon 1, consistent with Li et al [ 20 ]. While all PJS patients exhibited STK11 gene variations, some were VUS[ 21 , 22 ], and numerous STK11 gene VUS exist in the ClinVar database, with the majority being missense variations[ 23 ]. Understanding the relationship between these variations and PJS is challenging, complicating clinical decision-making, reproduction decisions, and genetic counseling for the patient[ 24 , 25 ], which may lead to increased psychological stress[ 26 ].…”

Peutz-jeghers syndrome: a case report

“…Hamartomatous polyps are not premalignant and are mostly located in small intestine, colon and stomach. 7 The life-time risk of gastrointestinal and non-gastrointestinal cancers is high and strict surveillance is necessary for early detection. 8 Our patient presented with intestinal obstruction due to jejunoileal intussuseption without any malignancy.…”

Asymptomatic Gastric Giant Polyp in a Boy with Peutz-Jeghers Syndrome Presented with Multiple Café Au Lait Traits

“…PJS is an autosomal dominant disease characterized by mucocutaneous pigmentation and hamartomatous polyps of the gastrointestinal tract. The most common location of these polyps is in the small intestine, colon, and stomach, respectively [ 1 , 2 ].…”

“…Multiple café au lait spots on his body in addition to the classic mucocutaneous macules around the mouth and the buccal mucosa was another unusual finding. Café au lait spots are more often associated with syndromes such as neurofibromatosis type 1 and McCune-Albright syndrome [ 1 , 2 ]. Unfortunately, skin lesions on our patient were not given attention from his parents and community pediatrician.…”

“…Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions. Coexistence of multiple café au lait spots is rare [ 1 , 2 ].…”