Congenital malformations - Edocr

CHAPTER 36 HIRSCHSPRUNG DISEASE 237
TABLE 36–2 Associated Anomalies in
Infants with Nonsyndromic Hirschsprung
Disease
Cardiovascular System 2.3–4.8%
• Atrial septal defect
• Ventricular septal defect
• Patent ductus arteriosus
• Tetralogy of Fallot
Genitourinary System 5.6–7.3%
• Renal agenesis
• Renal dysplasia
• Hypospadias
• Uretheral fistulas
Gastrointestinal System 3.3–3.9%
• Pyloric stenosis
• Meckel diverticulum
• Small bowel atresia
• Inguinal hernia
• Malrotation
• Imperforate anus
Central Nervous System 3.6–3.9%
• Microcephaly
• Dandy-Walker malformation
• Mental retardation
• Sensorineural hearing loss
mutation involve the cysteine residues on exon
10 which is known to predispose to the development
of MEN2A or FMTC. 8 In view of these findings,
a recent consensus statement from an international
group of endocrinologists recommended
RET exon10 mutation analysis in all children with
Hirschsprung disease, 9 but this recommendation
is not well accepted and is not the standard of
care yet. However, a strong consideration should
be given to genetic workup if there is a family history
of thyroid, parathyroid, or adrenal cancer.
MANAGEMENT AND PROGNOSIS
The mainstay of treatment is surgical which can
be done as an either single stage procedure or
in two stages depending on the length of the
aganglionic segment and the clinical condition
of the patient. The overall prognosis of an infant
with isolated Hirschsprung disease is very good.
Most infants achieve fecal continence. Long-term
problems include incontinence, stricture, recurrent
enterocolitis, rectal prolapse, perineal abscesses,
and require close follow-up. The prognosis of an
infant with the syndromic form of Hirschsprung
disease depends on the underlying syndrome.
Infants found to be positive for a genetic mutation
of the RET gene should be followed closely
for development of MEN2A.
GENETIC COUNSELING
The overall recurrence risk in siblings of an infant
with Hirschsprung disease is about 3–4%
which is about 200 times higher than the risk in
the general population. However, the recurrence
risk in a given family depends on the gender
of the proband and the sibling, the length
of aganglionic segment, the presence of associated
syndromes, and the underlying genetic mutation.
The recurrence risks for the sibling of a
patient with Hirschsprung disease are summarized
in Table 36-4. The risk to sibs is high when
the proband is female (Carter effect). Siblings of
female probands have a 360 times increased
risk and siblings of male patients have a 130-fold
risk of developing Hirschsprung disease. Prenatal
diagnosis is possible if the genetic mutation
within the family is known. However, because
the penetrance of single gene mutations is variable,
the clinical usefulness of genetic testing is
limited 3 and its role in counseling Hirschsprung
disease patients is not yet well-defined but
could be used in some situations to give more
accurate estimation of recurrence risks. For
example, the finding of a RET mutation in a
male proband with L-HSCR and the exclusion
of this mutation in the parents may allow lowering
of the recurrence risk from 13% to 17% to
less than 1%. 10