Background Hirschsprung’s disease (HSCR) is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth, causing great physical and mental pain to patients and their families. Studies have shown that more than 20 genes are involved in HSCR, and most cases of HSCR are sporadic. However, the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%. Furthermore, familial HSCR patients show incomplete dominance. We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families. Methods To find published references, we used the title/abstract terms “Hirschsprung” and “familial” in the PubMed database and the MeSH terms “Hirschsprung” and “familial” in Web of Science. Finally, we summarized 129 HSCR families over the last 40 years. Results The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR. The primary gene factors in the syndromic families are ret proto-oncogene (RET) and endothelin B receptor gene (EDNRB). Most families show incomplete dominance and are relevant to RET, and the RET mutation has 56% penetrance in familial HSCR. When one of the parents is a RET mutation carrier in an HSCR family, the offspring’s recurrence risk is 28%, and the incidence of the offspring does not depend on whether the parent suffers from HSCR. Conclusion Our findings will help HSCR patients obtain better genetic counseling, calculate the risk of recurrence, and provide new insights for future pedigree studies.

Background Hirschsprung’s disease (HSCR) is one of the most common malformations of the digestive tract. Patients with HSCR frequently manifest as having severe constipation and abdominal distension. The primary pathological feature of HSCR is the absence of ganglion cells in the distal bowel, and the arrangement of the circular and longitudinal muscles of the aganglionic segments is disorganized. To function properly, it requires an intact muscular layer as well as a neural network connection. Previous research has suggested that HSCR is a neurological disorder; however, HSCR may also be a muscular cell disorder of the intestinal smooth muscle. Methods To investigate the development rules of circular and longitudinal muscles and to research whether ENCCs affect smooth muscle function. αSMA immunohistochemistry was used to stain tissues of HSCR patients and HSCR model mice at different developmental stages. Results Under normal circumstances, the formation of circular muscles is later than that of longitudinal muscles, and the expression of αSMA in circular muscles is much lower than that in longitudinal muscles. The expression of αSMA in anganglionic segments of HSCR patients is much higher than that in the distal colon of normal control children. Conclusions Loss of ENCCs may influence the function of the circular muscles, αSMA is a biomarker for detecting the abnormal smooth muscle cell in Hirschsprung's disease patients' aganglionic segments.