Aicardi syndrome

* We describe the case of a patient with Rett syndrome, a syndrome characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy with constipation. At colonoscopy, multiple foci of tiny white, sessile, polypoid lesions were seen throughout the colon and rectum, mimicking the appearances of small hyperplastic or adenomatous polyps, associated with generalized melanosis coli. This is the first case to our knowledge describing melanosis coli in a patient with Rett syndrome. As melanosis pigment deposition is characteristically not seen in lymphoid tissue, the lymphoid tissue was identifiable at endoscopy as multiple white nodules mimicking generalized colonic polyposis throughout the colon. We discuss the likely mechanisms of lymphoid hyperplasia and coexistent melanosis coli in Rett syndrome.

(Arch Pathol Lab Med. 2001;125:1110-1112)

The patient we describe had Rett syndrome. This syndrome is characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy.1 Melanosis coli is a common endoscopic finding related to the use of anthracene-containing laxatives.2,3 Often, reticular areas are not stained because of the variation in pigment deposition. Mucosal lymphoid aggregates, adenomatous (dysplastic) mucosa, and cancers tend to show no accumulation of pigment, and therefore such foci appear endoscopically as white patches.4 We report the case of a patient with both Rett syndrome 5 and generalized melanosis coli. In this patient, colonoscopy showed diffuse nodular lymphoid hyperplasia of the large intestine that gave rise to a striking endoscopic appearance mimicking generalized colonic polyposis. We discuss the implications of this finding with respect to the known pathophysiology of Rett syndrome.

REPORT OF A CASE

A 40-year-old woman with Rett syndrome presented to her general practitioner with a long-standing history of abdominal pain, loss of appetite, and constipation requiring laxatives including senna. A complete blood count showed microcytic anemia that was subsequently attributed to menorrhagia. There was no clinical evidence of immunosuppression, and serum immunoglobulin levels and the results of a protein strip test were normal.

On examination, the patient had no palpable abdominal masses. The patient underwent flexible sigmoidoscopy and subsequent colonoscopy under general anesthesia because she had tolerated outpatient sigmoidoscopy poorly. These procedures revealed multiple white, sessile, nodular, polyplike lesions all less than 1 mm in size, scattered throughout the colon and rectum; in addition, the colon had an endoscopic appearance characteristic of melanosis coli (Figure 1). The results of gastroscopy and duodenal biopsy were normal. There was no evidence of villous abnormality or parasites on duodenal biopsy.

Colonic biopsies showed marked melanosis coli (Figure 2) with multiple foci of lymphoid follicular hyperplasia corresponding to the white nodular patches distributed throughout the colon and rectum (Figure 3). The lymphoid follicles did not stain for melanosis pigment, although there were multiple foci of melanosis pigment in the surrounding mucosa. The melanosis pigment was brown, finely granular, and periodic acid-Schiff positive, and it was present within macrophages in the lamina propria.

COMMENT

Colonic lymphoid hyperplasia is a common pathologic finding and is usually of no pathophysiologic significance. It has been described in a number of conditions including human immunodeficiency virus infection, Crohn disease, and hypogammaglobulinemia.4 In this case, the distribution of the melanosis pigment as shown in the endoscopic photograph (Figure 1) emphasizes the diffuse nature of the patient's diffuse nodular lymphoid hyperplasia of the colon and rectum.

Rett first discovered his eponymous syndrome in 1966, and Hagberg1 subsequently formulated diagnostic criteria for the syndrome in 1983. The syndrome results in a striking, progressive encephalopathy from the age of 7 to 18 months onward, before which normal development occurs. The developmental stagnation (standstill of developmental milestones in childhood) is followed by a rapid deterioration that initially progresses to severe dementia, autism, loss of purposeful use of the hands, jerky truncal ataxia, and microcephaly. After a period of stagnation, spastic paraparesis, vasomotor lower-limb disturbance, and epilepsy can occur. Rett syndrome is commonly associated with constipation.6 Constipation may be related to hypotonia or autonomic dysfunction, or it may be related to degenerative features that have been identified in the ultrastructure of the enteric ganglia from patients with Rett syndrome,7 although these features may be a nonspecific phenomenon.

To the best of our knowledge, neither lymphoid follicular hyperplasia nor melanosis coli has been previously described in patients with Rett syndrome. This is surprising because constipation and, by inference, laxative use with consequent melanosis coli must be common in patients with Rett syndrome. Melanosis coli characteristically involves all parts of the colon and rectum but tends to spare the regions of mucosa occupied by lymphoid nodules, polyps, and carcinomas.3 It has been recommended that during investigation of patients with melanosis coli for suspected mucosal lesions, biopsies should be taken of isolated areas lacking pigmentation if neoplasia is suspected.8 A possible explanation for the lack of published reports of melanosis coli in patients with Rett syndrome is that although Rett syndrome causes constipation, endoscopic examination of patients is probably unusual. Patients with Rett syndrome become easily upset by unfamiliar surroundings and situations and do not tolerate procedures well.

Anthraquinone laxatives have been documented to cause colonic structural damage; moreover, they are neurotoxins and presumably may affect intestinal ganglionic function and peristalsis.9 Large intestine mucosal lymphoid hyperplasia has been predominantly associated with immune system diseases,10 but there is no literature describing an association of immune deficiency with Rett syndrome.

Because patients with Rett syndrome characteristically experience constipation, it is logical to assume that melanosis coli must be common in these patients. The melanosis pigment spares lymphoid tissue. Therefore, in patients with generalized melanosis coli with other suspected mucosal pathology, it is imperative that biopsies of the suspect lesions be taken from nonmelanotic mucosa.

Dr Pearce is financially supported by Fresenius Ltd.

Accepted for publication March 2, 2001.

References

1. Hagberg B, Aicardi J, Dias K, Ramos 0. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls. Rett's syndrome: report of 35 cases. Ann Neurol. 1983;14:471-479.

2. Ghiadially FN, Walley VM. Melanoses of the gastrointestinal tract. Histopathology. 1994;25:197-207.

3. Goldman H. Other inflammatory disorders of the intestines. In: Ming SC, Goldman H, eds. Pathology of the Gastrointestinal Tract. Baltimore. Md: Williams and Wilkins; 1998:719-753.

4. Bharadhwaj G, Triadafilopoulos G. Endoscopic appearances of colonic lymphoid nodules: new faces of an old histopathological entity. Am J Gastroenterol. 1995;90:946-950.

5. Rett A. Uber ein eigenartiges hirnatrophisches Syndrom bei Hyperammoniamie in Kindesalter. Wien Med Wschr. 1966;116:723-738.

6. Budden SS. Rett syndrome: habilitation and management reviewed. Eur Child Adolesc Psychiatry. 1997;6(suppl):103-107.

7. Malandrini A, Hayek G, Villanova M, et al. Ultrastructural study of enteric ganglia in three patients with Rett syndrome. Brain Dev. 1998;20:586-588.

8. Davila AD, Willenbucher RF. Other diseases of the colon and rectum. In: Feldman M, Scharschmidt BF, Sleisenger MH, eds. Gastrointestinal and Liver Disease. New York, NY: WB Saunders; 1998:1977-2006.

9. Nelemans FA. Clinical and toxicological aspects of anthraquinone laxatives. Pharmacology. 1976:14(suppl 1):73-77.

10. Ell SR, Frank PH. Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease. Gastrointest Radio]. 1981;6:329-332.

Callum B. Pearce, MB ChB, MRCPI; Hilary Martin, MB BS; Hamish D. Duncan, MD, MRCP; Patrick M. Goggin, MD, FRCP; David N. Poller, MD, MRCPath

From the Queen Alexandra Hospital, Portsmouth, United Kingdom.

Reprints: David N. Poller, MD, MRCPath, Consultant Pathologist, Queen Alexandra Hospital, Portsmouth P06 3LY, United Kingdom (e-mail: david@poller.demon.co.uk).

Copyright College of American Pathologists Aug 2001
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