Anal Stenosis in York Platelet Syndrome: 2 Children With Constipation, a Previously Unreported Symptom

Salim Hommeida, MD
Michael Ishitani, MD
Imad Absah, MD
Volume 56 - Issue 4 - April 2016

Constipation is a common gastrointestinal complaint among children, with an estimated worldwide prevalence of 0.7% to 29.6% in the pediatric population.1 Constipation can lead to psychosocial consequences and poor school performance if it is not managed appropriately. The condition is categorized as either functional or organic, with the latter being more likely during the neonatal period.2 It is important to distinguish between these categories of constipation so as to avoid complications that can result from unmanaged cases. The differential diagnosis for organic constipation is broad, and the common etiologies are anatomic abnormalities, Hirschsprung disease, celiac disease, hypothyroidism, and myopathies.

Two pediatric patients with York platelet syndrome (YPS) were evaluated in the pediatric gastroenterology clinic for a history of chronic constipation. YPS is a very rare autosomal dominant syndrome with only 7 reported cases in the literature, 4 of which were reported in one family (Figure 1).3,4 YPS is characterized by thrombocytopenia and ultrastructural platelet abnormalities including giant opaque organelles, multilayered target bodies, an increased tubular network, and deficiency of platelet calcium (Ca2+) storage in delta granules.5


Figure 1. York platelet syndrome showed an autosomal dominant pattern of inheritance in 4 of the identified cases in a single family.

 

YPS is caused by a channelopathy in the Ca2+-selective release-activated Ca2+ channel due to a gain-of-function mutation in the stromal interaction molecule 1 gene (STIM1), which leads to a deficiency of platelet calcium storage, resulting in the formation of megakaryocytes and the structural abnormalities mentioned above.5 Laboratory study results in the reported YPS cases showed thrombocytopenia and elevated creatine kinase.3-5

Some of the clinical features of YPS in the reported cases include miosis, distal muscle atrophy, and atrophy of the extraocular muscles.5 No gastrointestinal tract manifestations had been reported as part of this syndrome until now.

Case 1

A 15-month-old boy with YPS presented with a history of refractory constipation since infancy. He had been born at term with no perinatal complications or delay in meconium passage. Beginning at approximately 4 months of age, after the introduction of solid food, the boy began to experience straining and painful defecation. Treatment with polyethylene glycol 3350 and other laxatives had been ineffective.

Results of laboratory studies showed thrombocytopenia and iron deficiency anemia, but normal electrolyte levels, normal thyroid function, and negative celiac serology results. Physical examination findings were normal except for tight anal stenosis. He underwent barium enema, the results of which showed a large amount of stool throughout the colon without transition zone or abnormal anatomy (Figure 2). Anorectal manometry results showed a normal rectosphincteric reflex, which excluded the presence of Hirschsprung disease (Figure 3).


Figure 2. York platelet syndrome showed an autosomal dominant pattern of inheritance in 4 of the identified cases.


Figure 3. Anorectal manometry results showed the presence of rectal inhibitory reflux.

 

He was referred to a pediatric surgeon and underwent anal dilation with Hegar dilators of up to 15 Fr without complications. Two months later, he continued to do well on daily use of a laxative containing polyethylene glycol 3350 without recurrence of constipation.

Case 2

A 3-year-old boy with a history of YPS presented with a history of chronic constipation since infancy, with persistent abdominal distension and infrequent bowel movements. He is the older sibling of the patient discussed in case 1 above. Treatment with laxatives had led to only mild improvement of his symptoms.

Laboratory test results revealed thrombocytopenia, normal electrolyte levels, normal thyroid function, and negative celiac serology results. Digital rectal examination revealed tight anal stenosis and a spastic anal sphincter that did not relax in response to the digital examination. Barium enema results showed a large amount of colonic fecal material without a transition zone. Anorectal manometry results showed a normal rectosphincteric reflex.

He was referred to a pediatric surgeon and underwent anal dilation with Hegar dilators of up to 15 Fr. He had immediate improvement in his bowel movement pattern without episodes of encopresis or stool withholding.

Cases 3 and 4

The father and the paternal grandmother of the patients described in cases 1 and 2 above also have YPS and have reported a similar history of chronic constipation with difficulty passing stool throughout their life. Neither has responded to medical management with numerous stool softeners and laxatives. Neither was interested in medical evaluation of their constipation.

While all of the members of this family who have YPS also have experienced constipation, it is unknown whether the father and/or the paternal grandmother have anal stenosis.

Discussion

YPS is a very rare autosomal dominant syndrome characterized by thrombocytopenia and ultrastructural platelet abnormality. None of the reported cases have had any documented gastrointestinal manifestations. The differential diagnosis of early-onset constipation includes anatomic defects, myopathies, and Hirschsprung disease.

Both of the pediatric patients passed stool within the first 48 hours of life, which makes Hirschsprung disease a less likely diagnosis, since 95% of neonates with Hirschsprung disease fail to pass meconium within the first 48 hours compared with approximately 1% of full-term newborns without the condition.6,7 The presence of normal rectosphincteric reflux excluded the diagnosis of Hirschsprung disease. Except for the anal stenosis found during physical examination, barium enema results excluded anatomic abnormalities such as microcolon in the patients.

Myopathy might have explained the patients’ symptoms; however, it is unlikely to be the sole etiology because of the absence of muscular weakness, the normal anorectal manometry results, and the improvement in symptoms after anal dilatation was performed. 

Laboratory study results also ruled out electrolyte abnormalities, lead poisoning, celiac disease, and hypothyroidism.

The presence constipation in two generations of this family with YPS suggests that constipation could be a gastrointestinal manifestation of the condition. In patients with YPS and constipation, careful assessment and physical examination should be done to exclude anal stenosis and other etiologies.

Salim Hommeida, MD, is a pediatric gastroenterologist in the Department of Pediatrics and Adolescent Medicine, Division of Pediatric Gastroenterology and Hepatology, at the Mayo Clinic College of Medicine in Rochester, Minnesota.

Michael Ishitani, MD, is a professor in the Department of Surgery, Division of Pediatric Surgery, at the Mayo Clinic College of Medicine in Rochester, Minnesota.

Imad Absah, MD, is an assistant professor in the Department of Pediatrics and Adolescent Medicine, Division of Pediatric Gastroenterology and Hepatology, at the Mayo Clinic College of Medicine in Rochester, Minnesota.

References:

  1. Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011;25(1):3-18.
  2. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014; 58(2):258-274.
  3. White JG, Gunay-Aygun M. The York platelet syndrome: a third case. Platelets. 2011;22(2): 117-134.
  4. White JG, Pakzad K, Meister L. The York platelet syndrome: a fourth case with unusual pathologic features. Platelets. 2013;24(1):44-50.
  5. Markello T, Chen D, Kwan JY, et al. York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. Mol Genet Metab. 2015;114(3):474-482.
  6. Swenson O, Sherman JO, Fisher JH. Diagnosis of congenital megacolon: an analysis of 501 patients. J Pediatric Surg. 1973;8(5):587-594.
  7. Sherry SN, Kramer I. The time of passage of the first stool and first urine by the newborn infant. J Pediatr. 1955;46(2):158-159.