A NOVEL WAY TO DIAGNOSE CYSTIC FIBROSIS IN THE NEONATE WITH A BOWEL OBSTRUCTION AND POSSIBLE MECONIUM ILEUS

Authors


28 July 2003

Dear Editor,

Paediatric surgeons and neonatologists are often confronted with a newborn baby with small bowel obstruction and suspected meconium ileus. Cystic fibrosis is an important and likely cause, but molecular diagnosis is rarely available in babies before intervention is required. If there were a simple clinical test for cystic fibrosis, it would confirm a diagnosis of meconium ileus even before a barium enema, and would alert the anaesthetist and surgeon.

There is a simple and reliable physical sign of cystic fibrosis in the male, that is, regression of the vas deferens. It has been well-documented that the majority of men with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD). However, CBAVD has been considered in recent years as an attenuated form of cystic fibrosis1. This theory is based on the discovery of the cystic fibrosis transmembrane regulator (CFTR) gene mutation in CBAVD.

Cystic fibrosis and CBAVD share a common genetic and embryological origin. Cystic fibrosis is an autosomal recessive disease resulting from mutation in the CFTR, a gene located on chromosome 7. The CFTR protein functions as a cyclic AMP-regulated chloride channel. CFTR mutations lead to degradation or malfunctioning of the protein, resulting in absent or defective chloride ion transport2. Recently, these mutations have also been recognized in CBAVD, with 75−80% of CBAVD patients having a CFTR gene defect2−4. The remaining group, without any recognizable CFTR mutation, is believed to have renal tract anomalies not associated with cystic fibrosis, known as Mayer-Kuster−Hauser−Rokitansky syndrome3,4.

There are two main theories to the pathogenesis of CBAVD in cystic fibrosis, based on the concept of defective chloride excretion. There is either growth disturbance of the Wolffian duct derivatives, which are more susceptible to defective chloride transport, or there is a process of atrophy due to obstruction of the ductal structures by viscous secretions. In the normal fetus, the Wolffian duct forms the epididymis, vas deferens and seminal vesicle under the control of gonadal androgens. By contrast, in fetuses with cystic fibrosis, the caudal epididymis and vas deferens undergo involution in mid-trimester3. The caput epididymis is spared from the pathophysiologic insult that affects the development of the distal two-thirds of the epididymis, the vas deferens, and the seminal vesicles, due to its derivation from a different embryologic precursor5.

At birth, the head of the epididymis is palpable, but the caudal epididymis and vas deferens are absent. The latter is readily determined by careful palpation of the neck of the scrotum, where the vas and gonadal vessels normally can be felt as two separate structures. The vas feels like a thin cord which can be rolled between the finger and thumb (Fig. 1).

Figure 1.

Illustration of the scrotal examination of a neonate. (a) Normal scrotal neck examination, with the vas and the gonadal vessels palpable as two separate structures. (b) Scrotal examination of a neonate with cystic fibrosis, with the vas and the tail of the epididymis missing, and the epididymal caput enlarged.

Bilateral absence of the vas deferens at the scrotal neck, combined with absence of the caudal epididymis, is a simple, quick and reliable physical sign of cystic fibrosis. This is true especially when a neonate presents with bowel obstruction − one only has to feel the external male genitalia, and the diagnosis of meconium ileus can be made. However, there is one drawback − it can be applied to only half the population!

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