Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Single-stage Modified Duhamel procedure for Hirschsprung’s disease: Our experience

Introduction: Primary single-stage pull-through for Hirschsprung's disease (HD) has been reported to give comparable surgical outcomes to staged operations with less morbidity. Herein, we present our experience with single-stage Modified Duhamel procedure for management of HD. Patients and Methods: This was a review of 48 cases of HD who underwent singlestage Modified Duhamel procedure without a protective colostomy. Results: The age at surgery ranged from 6 months to 10 years (median - 9 months, mean - 2.3 years). The average weight of the child was 7.2 kg (range, 4.9-22 kg). 38 (79.2%) patients had classical rectosigmoid HD, the rest being long segment HD (the proximal most level being the splenic flexure). The average duration of surgery was 175 minutes (range, 130-245 minutes). The average blood loss was 45 ml. The average hospital stay was 7.2 days (range: 6-10 days). The major postoperative complications (n=3) included postoperative adhesive intestinal obstruction, anastomotic leak and persistent constipation due to residual aganglionosis. Each required a re-exploration. Minor complications included surgical site infection (n=3) and post-operative enterocolitis (n=3), which were managed conservatively. Six patients had constipation for a limited period post-operatively. All patients have a satisfactory functional outcome and normal development and growth. Conclusions: For HD, we recommend that single-stage Modifi ed Duhamel procedure should be the preferred approach in view of its low morbidity, satisfactory functional outcome and avoidance of stoma, multiple surgeries and economic benefit in view of decreased hospital stay