J Korean Med Sci.  2011 Feb;26(2):312-315. 10.3346/jkms.2011.26.2.312.

Haddad Syndrome with PHOX2B Gene Mutation in a Korean Infant

• Lee CW
• Lee JH
• Jung EY
• Choi SO
• Kim CS
• Lee SL
• Kim DK

• KMID: 1782126
• DOI: http://doi.org/10.3346/jkms.2011.26.2.312

Abstract

Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is an extremely rare disorder with variable symptoms. Recent studies described that congenital central hypoventilation syndrome had deep relation to the mutation of the PHOX2B gene in its diagnosis and phenotype. We report a newborn male infant with clinical manifestations of recurrent hypoventilation with hypercapnea and bowel obstruction. These clinical manifestations were compatible with congenital central hypoventilation syndrome and Hirschsprung's disease, and polyalanine 26 repeats in the PHOX2B gene supported the diagnosis of congenital central hypoventilation. We described a first case of Haddad syndrome in Korean and its clinical and genetic characteristics were discussed.

Keyword

Congenital Central Hypoventilation Syndrome; Hirschsprung Disease; Haddad Syndrome; PHOX2B gene

MeSH Terms

Asian Continental Ancestry Group
Base Sequence
DNA Mutational Analysis
Hirschsprung Disease/diagnosis/genetics/pathology
Homeodomain Proteins/*genetics
Humans
Hypoventilation/congenital/diagnosis/genetics
Infant, Newborn
Male
Molecular Sequence Data
*Mutation
Sleep Apnea, Central/diagnosis/genetics
Transcription Factors/*genetics

Figure

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  Fig. 1 Diagnosis of Hirschsprung's disease. (A) Barium enema showing transitional zone (arrow) in the middle of the sigmoid colon. (B) Frozen section of the biopsy showing the absence of ganglion cells. (C) Enzyme histochemistry showing aberrant acetylcholine esterase.

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  Fig. 2 The polyacrylamide gel electrophoresis of the PHOX2B gene SSCP profiles in Haddad syndrome and his family. A heterozygous mutation (232 bp and 250 bp) was found in the patient compared to the single strands in his family and normal samples (232 bp). SM, size marker; HS, Haddad syndrome; F, father; M, mother; N1, N2, and N3, normal controls.

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  Fig. 3 DNA sequencing of heterozygous mutation of the PHOX2B gene showing expanded polyalanine 26 repeats. In the patient with Haddad syndrome, normal allele (A) had 20 repeats (red line) and the mutation allele (B) had +6 repeats (blue line) of the polyalanine sequence.

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