: 2014  |  Volume : 1  |  Issue : 3  |  Page : 244--245

Rare association of lissencephaly with hirschprung's disease

Aliza Mittal, Rachna Sehgal, Ratan Gupta, Shobha Sharma, Kailash Chander Aggarwal 
 Department of Pediatrics, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India

Correspondence Address:
Rachna Sehgal
Department of Pediatrics, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi

How to cite this article:
Mittal A, Sehgal R, Gupta R, Sharma S, Aggarwal KC. Rare association of lissencephaly with hirschprung's disease.Astrocyte 2014;1:244-245

How to cite this URL:
Mittal A, Sehgal R, Gupta R, Sharma S, Aggarwal KC. Rare association of lissencephaly with hirschprung's disease. Astrocyte [serial online] 2014 [cited 2020 Sep 27 ];1:244-245
Available from:

Full Text


Constipation is a common co-morbidity seen in pediatric neurological disorders and is often due to associated skeletal muscle incoordination, skeletal deformities, and prolonged immobility per seor drugs used in the treatment of neurological illnesses. Rarely does one think of Hirschsprung's disease (HSCR) as a cause of constipation in these children.

Lissencephaly (LIS) and HSCR disease both have been described in the literature widely in isolation. Both the conditions are attributed to neurocristopathies. Their co-occurrence in a child is very uncommon in the literature with only three cases reported so far. Whether this association is actually by chance or is overlooked and is attributed to other etiologies of constipation is still not proven. However, this co-occurrence has been emphasized rarely. Therefore, we describe this rare association.

We describe here a 7-month-old girl child born at term by normal vaginal delivery and with no adverse antenatal or perinatal factors. She presented first time at 6 months with recurrent multifocal clonic and tonic seizures with global developmental delay in the form of no head holding, no reaching out for objects, no social smile, and only crying as a means of vocalization. There was a history of constipation since birth which required frequent enemas. Physical examination revealed no facial dysmorphism or neurocutaneous markers. The occipitofrontal circumference was 34 cm (microcephaly) and spastic quadriparesis was present.

The child was investigated and started on anti-epileptics. The contrast-enhanced computed tomography scan was suggestive of LIS [Figure 1]. However, the electroencephalogram was normal.{Figure 1}

On second and present admission at 7 months of age, she complained of constipation for the past 3 weeks. On examination, child had a distended abdomen and bowel sounds were present. An ultrasound revealed presence of free fluid in the peritoneal cavity. Barium enema was performed, and it revealed gross dilatation of the descending and sigmoid colon. A 24 h delayed film was suggestive of persistence of dilatation and narrowing of the recto-sigmoid junction. These findings were suggestive of HSCR disease [Figure 2].{Figure 2}

A high sigmoid loop colostomy was performed, and peroperative findings were suggestive of classic HSCR disease with spastic recto-sigmoid junction and dilated sigmoid and descending colon.

A biopsy taken from the spastic recto-sigmoid zone had mild mucosal inflammation, and no ganglion cells were present in this region. A biopsy specimen from the colostomy site was suggestive of mild nonspecific enteritis with congestion and ganglion cells were present.

The child was discharged on anti-epileptics, care of colostomy and parental counseling.


Constipation, defined as opening of the bowels less frequently than once in every 3 days, has been reported in as high as 26% of neurologically impaired children. [1] The most common factors contributing to constipation that have been described in this group of children include : Decreased mobility, decreased dietary fiber and liquid intake due to immature oral motor skills and/or dysphagia, abdominal muscle weakness, decreased motility of the lower bowel, abnormal behavioral responses to the presence of stool in the rectum, resulting in stool holding.

Most of the times, one would attribute constipation in these children to the above-mentioned factors as was done in the present case initially. However, it was later found to be due to HSCR disease.

Hirschsprung's disease (aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is characterized by the absence of the enteric ganglia along a variable length of the intestine. It is regarded as the consequence of the premature arrest of the craniocaudal migration of vagal neural crest cells in the hindgut between the 5th and 12th week of gestation to form the enteric nervous system and is, therefore regarded as a neurocristopathy. [2]

Hirschsprung's disease occurs as an isolated trait in 70% of patients, is associated with a chromosomal abnormality in 12% of the cases, and with additional congenital anomalies in 18% of the cases. The most common chromosomal abnormality is trisomy 21, but there are other rare recurrent deletions and duplications including 13q22 (deletes EDNRB), 2q22-23 (deletes ZFHX1B) and 17q21-q23. [2]

A wide spectrum of additional isolated anomalies has been described among HSCR cases, with an incidence varying from 5% to 30% according to a series. No constant pattern is observed and these anomalies include distal limb, sensorineural deafness, and malformations of skin, central nervous system, genital, kidney, and cardiac systems. However, cardiac defects and mostly atrio or ventriculoseptal defects are found with an incidence of 5% of HSCR cases, once patients with trisomy 21 and HSCR are excluded. [1]

On the other hand, LIS is a spectrum of brain malformations due to diffuse neuronal migration disorder. [3] It is characterized by a smooth or nearly smooth cerebral cortex. It encompasses gyral malformations ranging from complete agyria to regional pachygyria, comprising with subcortical band heterotopia. Gene mutation of tubulin alpha-1A (TUBA1A), a critical component of microtubules of the cytoskeleton, impairs neural migration and causes LIS. [4] The genetic mutation in our case could not, however, be identified due to resource constraints.

The most striking feature of our case is the co-occurrence of LIS with HSCR. Although several concomitant malformations with LIS and HSCR disease individually have been described in the literature but the occurrence together of both of these entities has been very uncommon. Only two other cases with this association have been reported. The first case also showed microcephaly and tetralogy of fallot, although the underlying gene mutation was unknown. [3] The second was an association of LIS with classical HSCR disease, and the underlying mutation was found to be TUBA1A. [3] Both LIS and HSCR are a form of neuronal migration defects and thus may occur together in a given patient. Hence, it is important that surgical causes of constipation should also be thought of in these neurologically challenged children once medical causes are ruled out.


1Sullivan PB, Lambert B, Rose M, Ford-Adams M, Johnson A, Griffiths P. Prevalence and severity of feeding and nutritional problems in children with neurological impairment : Oxford feeding study. Dev Med Child Neurol 2000;42:674-80.
2Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, et al. Hirschsprung disease, associated syndromes and genetics : A review. J Med Genet 2008;45:1-14.
3Tanteles GA, Kurup B, Rauch A, Splitt MP. Microcephaly, lissencephaly, Hirschsprung disease and tetralogy of Fallot : A new syndrome? Clin Dysmorphol 2006;15:107-10.
4Hikita N, Hattori H, Kato M, Sakuma S, Morotomi Y, Ishida H, et al. A case of TUBA1A mutation presenting with lissencephaly and Hirschsprung disease. Brain Dev 2014;36:159-62.