A 3-week old baby girl is sent to your emergency department after being seen by their pediatrician for irritability, poor feeding, and a seizure just prior to arrival at the pediatrician’s office. Vital signs are BP-103/73, HR-137, RR-25, O2-100% on room air, and Temp-39.2oC (102.5oF). Physical examination reveals a lethargic infant with decreased motor tone and a full, bulging frontal fontanelle. What is the most important diagnostic study to obtain and what is the empiric treatment of choice while awaiting results?
Other Known Aliases – congenital aganglionic megacolon, congenital intestinal aganglionosis
Definition – motor disorder of the intestines due to failure of the neural crest cells, which are precursors of ganglion cells) to fully migrate during embryonic development of the colon.
Clinical Significance – As a result of this aganglionosis of the colon, the distal intestines are unable to relax and cause a functional obstruction. Children affected by this condition fail to pass their meconium stool in the first 48 hours of life and may have abdominal distention, bilous emesis, and/or enterocolitis. Diagnosis is made with contrast enema and suction rectal biopsy.
History – Named after Harald Hirschprung (1830-1916), who was a Danish physician and received his medical doctorate from the University of Copenhagen in 1855. In 1870, he became the first Danish pediatrician and was appointed chief physician of Queen Louisa Hospital for Children in 1879. He presented his eponymous findings at the Berlin Congress for Children’s Diseases in 1886 where he described two infants who had died from “constipation associated with dilation and hypertrophy of the colon”. He published his findings a year later in an article entitled “Stuhlträgheit Neugeborener in Folge von Dilatation und Hypertrophie des Colons”. Other notable contributions of Dr. Hirschprung include being one of the first physicians to successfully reduce intussuception by pneumatic means and being an advocate for free health care for all children.
References
Firkin BG and Whitwirth JA. Dictionary of Medical Eponyms. 2nd ed. New York, NY; Parthenon Publishing Group. 1996.
Bartolucci S, Forbis P. Stedman’s Medical Eponyms. 2nd ed. Baltimore, MD; LWW. 2005.
Yee AJ, Pfiffner P. (2012). Medical Eponyms (Version 1.4.2) [Mobile Application Software]. Retrieved http://itunes.apple.com.
Hirschsprung H. Stuhlträgheit Neugeborener in Folge von Dilatation und Hypertrophie des Colons. [Constipation of newborns as a result of dilatation and hypertrophy of the colon] Jahrbuch für Kinderheilkunde und physische Erziehung 1888;27:1–7
Hirschsprung H. Fälle von Angeborenen Pylorusstenose, Beobachtet bei Säuglingen. Jahrbuch für Kinderheilkunde und physische Erziehung 1888;27:61-8
Lister J. Hirschsprung: the man and the disease. Journal of the Royal College of Surgeons of Edinburgh. 1977; 22(6):378-84. [pubmed]
Skaba R. Historic milestones of Hirschsprung’s disease (commemorating the 90th anniversary of Professor Harald Hirschsprung’s death). Journal of pediatric surgery. 2007; 42(1):249-51. [pubmed]
Roed-Petersen K, Erichsen G. The Danish pediatrician Harald Hirschsprung. Surgery, gynecology & obstetrics. 1988; 166(2):181-5. [pubmed]
Motor gut disorder characterized by failure of the neural crest cells (which are precursors to the enteric ganglion cells) to fully migrate to the distal portions of the colon.
Most accepted theory is there is a defect in the craniocaudal migration of neuroblasts that occurs between 4-7 weeks gestation
12 genetic mutations currently identified predominantly affecting the RET proto-oncogene
Produces a tyrosine kinase protein that transduces growth and differentiation signals in developing tissues
The absence of these cells in the mucosal and muscular layer of the colon results in the failure of the colonic muscles to relax.
Epidemiology
Occurs in 1:5000 live births
Male:Female ratio of 3-4:1
80% of cases affect the rectosigmoid
junction (termed short-segment disease)
15-20% of cases extend to the proximal
sigmoid colon (termed long-segment disease)
<5% of cases affect the entire
colon
Associated Syndromes
Trisomy 21(up to 16% of cases)
Bardet-Biedi
Cartilage-hair hypoplasia
Congenital central hypoventilation
syndrome
Familial dysautonomia
Multiple endocrine neoplasia type 2
Mowat-Wilson
Smith-Lemli-Opitz
Waardenburg
Associated Congenital Anomalies
Up to 25% of Hirschsprung patients have other
congenital anomalies including:
Genitourinary (20-40%)
Hydronephrosis, renal agenesis
Visual/Hearing Impairment (5-40%)
Most are refractive errors
Congenital Heart Disease (50%)
Almost exclusively in syndromic
Hirschsprung
Anorectal Malformations
Signs and Symptoms
Failure to pass meconium in first 48 hours
100% of normal full-term infants pass meconium in first 48 hours in contrast to only 10-40% of infants with Hirschsprung
Abdominal distention
Squirt/Blast Sign
Explosive expulsion of gas and stool after digital rectal examination
Bilious emesis
Enterocolitis and volvulus are rare, life-threatening complications or presentations
Most are diagnosed in the neonatal period, but less-severe short-segment disease can present as late as 3 years old
Diagnostic Work-Up
Indications for testing include:
Symptoms of obstruction
Failure to pass meconium after 48 hours
Constipation and Trisomy 21 (or other associated syndrome)
Constipation and physical examination suggestive of Hirschsprung
If fever, lethargy, and/or obstipation are present, emergent evaluate for enterocolitis is needed
Studies
“Unprepped” contrast enema
Identification of transition zone
Change from normal caliber/narrowed rectum to dilated proximal colon
Anorectal manometry
Useful in ultrashort segment disease
Can approach 100% NPV is performed properly
Suction rectal biopsy
GOLD STANDARD for diagnosis
Location should be 2cm above the level of the dentate line
Histology findings
Presence of hypertrophic nerve fibers
Increased acetylcholinesterase
activity or staining in the muscularis mucosae
Decreased or absent
calretinin-immunoreactive fibers in the lamina propria
Abnormal acetylcholine esterase (AchE)-positive nerve fibers (brown) in the mucosa
Treatment
Surgery is the mainstay of treatment
Resect the affected segment
Bring the normal ganglionic bowel down to anus
Preserve internal sphincter function
Originally, this was an open, two-stage procedure with a diverting colostomy
To allow the dilated segement to decompress back to normal size
Now, it can be performed as a single-stage operation either laparoscopically or transanally
3 types of Pull-Through Procedures
Complications
Anastomotic stricture, constipation, incontinence, or enterocolitis
The Cottage Physician (1893)
Chapter – Children and Their Diseases
References
Hoffenberg EJ, Furuta GT, Kobak G, Walker T, Soden J, Kramer RE, Brumbaugh D. Gastrointestinal Tract. In: Hay, Jr. WW, Levin MJ, Deterding RR, Abzug MJ. eds. Current Diagnosis & Treatment: Pediatrics, 24e New York, NY: McGraw-Hill
Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. American journal of human genetics. 1990; 46(3):568-80. [pubmed]
Fu M, Tam PK, Sham MH, Lui VC. Embryonic development of the ganglion plexuses and the concentric layer structure of human gut: a topographical study. Anatomy and embryology. 2004; 208(1):33-41. [pubmed]
Goldstein AM, Hofstra RM, Burns AJ. Building a brain in the gut: development of the enteric nervous system. Clinical genetics. 2013; 83(4):307-16. [pubmed]
Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. Journal of medical genetics. 2008; 45(1):1-14. [pubmed]
Pini Prato A, Rossi V, Mosconi M, et al. A prospective observational study of associated anomalies in Hirschsprung’s disease. Orphanet journal of rare diseases. 2013; 8:184. [pubmed]
Sarioglu A, Tanyel FC, Büyükpamukçu N, Hiçsönmez A. Hirschsprung-associated congenital anomalies. European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery … [et al] = Zeitschrift fur Kinderchirurgie. 1997; 7(6):331-7. [pubmed]
Khan AR, Vujanic GM, Huddart S. The constipated child: how likely is Hirschsprung’s disease? Pediatric surgery international. 2003; 19(6):439-42. [pubmed]
Arshad A, Powell C, Tighe MP. Hirschsprung’s disease. BMJ (Clinical research ed.). 2012; 345:e5521. [pubmed]
Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of pediatric gastroenterology and nutrition. 2006; 43(3):e1-13. [pubmed]
Putnam LR, John SD, Greenfield SA, et al. The utility of the contrast enema in neonates with suspected Hirschsprung disease. Journal of pediatric surgery. 2015; 50(6):963-6. [pubmed]
Meinds RJ, Trzpis M, Broens PMA. Anorectal Manometry May Reduce the Number of Rectal Suction Biopsy Procedures Needed to Diagnose Hirschsprung Disease. Journal of pediatric gastroenterology and nutrition. 2018; 67(3):322-327. [pubmed]
Alizai NK, Batcup G, Dixon MF, Stringer MD. Rectal biopsy for Hirschsprung’s disease: what is the optimum method? Pediatric surgery international. 1998; 13(2-3):121-4. [pubmed]
Hackam DJ, Grikscheit T, Wang K, Upperman JS, Ford HR. Pediatric Surgery. In: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. eds. Schwartz’s Principles of Surgery, 10e New York, NY: McGraw-Hill; 2015
You are consulted to see a 2-day old baby boy for failure to pass the first meconium stool and an episode of bilious emesis. He was 37-weeks gestation at the time of a normal spontaneous vaginal delivery without any complications. Physical examination reveals a distended abdomen and digital rectal exam results in an explosive expulsion of stool and gas. A contrast enema was ordered and is attached. What is the specific cause (not the diagnosis) of this infant’s condition and what is the next diagnostic step?
Answer
This infant has congenital aganglionic megacolon, or Hirschprung Disease. It is caused by the failure of the neural crest cells (precursors to enteric ganglion cells) to migrate completely during intestinal development in utero. This results in the failure of the colon to be able to relax and causes a functional obstruction.
Diagnosis is made with bedside suction rectal biopsy 2cm above the level of the dentate line. Confirmatory findings on histology are abnormal acetylcholine esterase-positive nerve fibers in the mucosa.
Definition – This syndrome is part of the Autism Spectrum Disorder (ASD) classification in DSM-V, but still is a distinct entity in the WHO International Classification of Disease. It is characterized by persistent impairment in reciprocal social communication and social interaction with restricted, repetitive patterns of behavior, interests, or activities.
DSM-IV Diagnostic Criteria
Clinical Significance – Children diagnosed with Asperger syndrome, or high-functioning ASD, have varying degree of social and/or behavioral impairments. It is on the lower end of the ASD spectrum and these children often have normal to higher level of measured intelligence at school, but struggle with social interactions, following specific directions, and meeting deadlines, which then negatively impact their progression through school. Early identification by school and medical staff can mitigate these deficiencies and help these children flourish in their formative years.
History – Named after Johann Friedrich Karl Asperger (1906-1980), who was an Austrian pediatrician and received his medical doctorate from the University of Vienna in 1931. He published extensively on behavioral disorders in children and termed the phrase “autistic psychopathy” in 1944 based on earlier work by Russian neurologist Grunya Sukhareva. His work garnered little contemporary acclaim and it wasn’t until Lorna Wing, an English researched, proposed the condition as Asperger’s syndrome in 1981. This caused a resurgence in translating Asperger’s work in the early 1990’s and inclusion in the DSM-IV in 1994. As a result of this increased fervor into his work, it was also discovered that Asperger was a eugenicist during the Nazi campaign, believed that “in the majority of the cases the positive aspects of autism do not outweigh the negative ones”, and even sent children from his center to the Spiegelgrund clinic, which participated in euthanasia program of the Nazi regime.
Personal Side Note – I have been struggling recently on whether to include eponyms that were named after individuals that achieved historical and medical notoriety through abhorrent means. I had originally planned NOT to give any of these individuals further recognition on the podcast, but I feel I would be doing a disservice to the patients that were affected by these individuals. As a result, I will publish this disclaimer on these episodes and a statement that this eponym will no longer be used on the blog or podcast after the ep-pain-nym segment and ask that you do the same.
References
Firkin BG and Whitwirth JA. Dictionary of Medical Eponyms. 2nd ed. New York, NY; Parthenon Publishing Group. 1996.
Bartolucci S, Forbis P. Stedman’s Medical Eponyms. 2nd ed. Baltimore, MD; LWW. 2005.
Yee AJ, Pfiffner P. (2012). Medical Eponyms (Version 1.4.2) [Mobile Application Software]. Retrieved http://itunes.apple.com.
You are consulted to see a 2-day old baby boy for failure to pass the first meconium stool and an episode of bilious emesis. He was 37-weeks gestation at the time of a normal spontaneous vaginal delivery without any complications. Physical examination reveals a distended abdomen and digital rectal exam results in an explosive expulsion of stool and gas. A contrast enema was ordered and is attached. What is the specific cause (not the diagnosis) of this infant’s condition and what is the next diagnostic step?
Other Known Aliases – Fallot’s tetrad, Fallot’s syndrome, Steno-Fallot tetralogy
Definition – Congenital cyanotic heart disease due to ventriculo-septal defect, pulmonary stenosis, right ventricular hypertrophy, and overiding aorta.
History – Named after Etienne-Louis Arthur Fallot (1850-1911), who was a French physician and received his medical doctorate from the University of Marseille in 1867. He described this tetrad in 1888 in an article entitled “Contribution à l’anatomie pathologique de la maladie bleue (cyanose cardiaque)” using previous observations from the work of Dutch anatomist Neils Stenson (1638-1686). Unfortunately, Fallot’s work garnered little contemporary acclaim and it wasn’t until Dr. Paul Dudley White (of WPW fame) translated and republished Fallot’s work in his landmark textbook “Heart Disease” in 1931.
References
Firkin BG and Whitwirth JA. Dictionary of Medical Eponyms. 2nd ed. New York, NY; Parthenon Publishing Group. 1996.
Bartolucci S, Forbis P. Stedman’s Medical Eponyms. 2nd ed. Baltimore, MD; LWW. 2005.
Yee AJ, Pfiffner P. (2012). Medical Eponyms (Version 1.4.2) [Mobile Application Software]. Retrieved http://itunes.apple.com.
