Haddad Syndrome: A Case Report in a Filipino Infant

Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS) occurs with Hirschsprung’s disease. It is extremely rare with only more than 60 cases reported in the worldwide literature. We report on a Filipino newborn male infant who presented with signs and symptoms of progressive abdominal enlargement, bowel obstruction, and recurrent hypoventilation. The diagnosis of Haddad syndrome was made clinically and confirmed by sequence analysis of the PHOX2B gene which showed a 27repeat heterozygous expansion of the polyalanine-coding region. All CCHS patients require assisted ventilation especially during sleep to prevent lung atelectasis and other complications. An early diagnosis and confirmation by genetic testing is vital for proper management of affected patients.

Download Full-text

CONGENITAL CENTRAL HYPOVENTILATION SYNDROME, CAUSED BY DE NOVO DELETION IN THE PHOX2B GENE

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2019-98-2-235-238 ◽

2019 ◽

Vol 98 (2) ◽

pp. 235-238

Author(s):

S.V. Dumova ◽

◽

N.A. Semenova ◽

O.L. Chugunova ◽

O.A. Babak ◽

...

Keyword(s):

De Novo ◽

Congenital Central Hypoventilation Syndrome ◽

Phox2b Gene ◽

Central Hypoventilation ◽

Hypoventilation Syndrome

Download Full-text

Congenital Central Hypoventilation Syndrome: A Comprehensive Review and Future Challenges

Journal of Respiratory Medicine ◽

10.1155/2014/856149 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8

Author(s):

Karin Ljubič ◽

Iztok Fister ◽

Iztok Fister

Keyword(s):

Ventilatory Support ◽

Congenital Central Hypoventilation Syndrome ◽

Phox2b Gene ◽

Central Controller ◽

Future Challenges ◽

The Central Nervous System ◽

Central Hypoventilation ◽

Hypoventilation Syndrome ◽

Cardiovascular Functions

Congenital central hypoventilation syndrome is a disorder predisposed by a paired-like homebox PHOX2B gene. A mutation in the PHOX2B gene is a requisite when diagnosing congenital central hypoventilation syndrome. This mutation is identified in 93–100% of diagnosed patients. The mutation regarding this disorder affects the sensors, the central controller, and the integration of the signals within the central nervous system. This, inter alia, leads to insufficient ventilation and a decrease in PaO2, as well as an increase in PaCO2. Affected children are at risk during and after the neonatal period. They suffer from hypoventilation periods which may be present whilst sleeping only or in more severe cases when both asleep and awake. It is important for clinicians to perform an early diagnosis of congenital central hypoventilation in order to prevent the deleterious effects of hypoxaemia, hypercapnia, and acidosis on the neurocognitive and cardiovascular functions. Patients need long-term management and appropriate ventilatory support for improving the qualities of their lives. This paper provides a detailed review of congenital central hypoventilation syndrome, a congenital disorder that is genetic in origin. We describe the genetic basis, the wider clinical picture, and those challenges during the diagnosis and management of patients with this condition.

Download Full-text

A Case of Congenital Central Hypoventilation Syndrome with PHOX2B Gene Mutation in a Korean Neonate

Journal of Korean Medical Science ◽

10.3346/jkms.2010.25.8.1237 ◽

2010 ◽

Vol 25 (8) ◽

pp. 1237 ◽

Cited By ~ 4

Author(s):

Kyoung-Ah Kwon ◽

Su-Eun Park ◽

Shin-Yun Byun ◽

Shine-Young Kim ◽

Sang-Hyoun Hwang

Keyword(s):

Gene Mutation ◽

Congenital Central Hypoventilation Syndrome ◽

Phox2b Gene ◽

Central Hypoventilation ◽

Hypoventilation Syndrome

Download Full-text

A Case of Congenital Central Hypoventilation Syndrome with a Novel Mutation of the PHOX2B Gene Presenting as Central Sleep Apnea

Journal of Clinical Sleep Medicine ◽

10.5664/jcsm.3542 ◽

2014 ◽

Vol 10 (03) ◽

pp. 327-329 ◽

Cited By ~ 5

Author(s):

Yuko Amimoto ◽

Kenji Okada ◽

Hiroshi Nakano ◽

Ayako Sasaki ◽

Kiyoshi Hayasaka ◽

...

Keyword(s):

Sleep Apnea ◽

Novel Mutation ◽

Central Sleep Apnea ◽

Congenital Central Hypoventilation Syndrome ◽

Phox2b Gene ◽

Central Hypoventilation ◽

Hypoventilation Syndrome

Download Full-text

Hirschsprung’s Disease: Two Cases of Total Intestinal Aganglionosis

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.159 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S73-S73

Author(s):

V Ramachandran ◽

J Nguyen ◽

C Caruso ◽

D Rao

Keyword(s):

Small Bowel ◽

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Ganglion Cells ◽

Ileocecal Valve ◽

Male Infant ◽

Congenital Central Hypoventilation Syndrome ◽

Renal Anomalies ◽

Central Hypoventilation ◽

Hypoventilation Syndrome

Abstract Introduction/Objective Hirschsprung’s disease is a disorder associated with an absence of ganglion cells in a segment of the bowel. Total colonic and small bowel aganglionosis occurs in less than 1% of all Hirschsprung’s disease patients. Even rarer is the finding of Haddad syndrome, the coexistence of congenital central hypoventilation syndrome and Hirschsprung’s disease. Congenital central hypoventilation syndrome has approximately 1,000 reported cases, with colonic aganglionosis being associated with 15-20% of those cases. The prevalence of Hirschsprung’s disease with congenital renal anomalies may be another underreported finding. Methods Here, we report two rare cases of Hirschsprung’s disease with significant extension in the small bowel. One case involves a 38-week gestational age male infant admitted for apnea and another case involves 39-week gestational age female infant admitted for vomiting. Results Both infants had rectal suction biopsies confirming the absence of ganglion cells. The male infant had mapping biopsies which histologically showed hypertrophic nerve fibers and an absence of ganglion cells in the colon extending up to 70 cm proximal to the ileocecal valve. Calretinin immunostaining confirmed aganglionsis. Genetic testing showed a PHOX2B gene mutation carrying 32 polyalanine repeat mutations, confirming a diagnosis of congenital central hypoventilation syndrome coexisting with Hirschsprung’s disease. The female infant had intraoperative frozen sections that identified ganglion cells throughout the colon. On permanent sections, there was an absence of ganglion cells in the upper rectum extending up to 65 cm proximal to the ileocecal valve. She also was noted to have agenesis of the left kidney and a urachal remnant. Genetic testing was negative for RET mutations. Conclusion Overall, these cases provide further information on a rare variant of Hirschsprung’s disease that includes significant portions of the small bowel. Additionally, this study adds to the documented reports of Haddad syndrome and the connections between renal anomalies with Hirschsprung’s disease. Last, this series alludes to the difficulties of frozen section diagnosis of this disease.

Download Full-text

Congenital central hypoventilation syndrome and the PHOX2B gene: A model of respiratory and autonomic dysregulation

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2010.06.013 ◽

2010 ◽

Vol 173 (3) ◽

pp. 322-335 ◽

Cited By ~ 49

Author(s):

Pallavi P. Patwari ◽

Michael S. Carroll ◽

Casey M. Rand ◽

Rajesh Kumar ◽

Ronald Harper ◽

...

Keyword(s):

Congenital Central Hypoventilation Syndrome ◽

Autonomic Dysregulation ◽

Phox2b Gene ◽

Central Hypoventilation ◽

Hypoventilation Syndrome

Download Full-text

Haddad Syndrome: A Case Study

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.24.4.41 ◽

2005 ◽

Vol 24 (4) ◽

pp. 41-44 ◽

Cited By ~ 1

Author(s):

Lisa Shuman ◽

Diane Youmans

Keyword(s):

Rare Condition ◽

Alveolar Ventilation ◽

Congenital Central Hypoventilation Syndrome ◽

Newborn Period ◽

Neural Crest Development ◽

Common Etiology ◽

Central Hypoventilation ◽

Hypoventilation Syndrome ◽

Haddad Syndrome

Hirschsprung’s disease (HD), also known as congenital aganglionic megacolon, is a relatively common cause of congenital obstruction of the colon. Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare condition involving failed autonomic respiration in the absence of cardiorespiratory disease resulting in inadequate alveolar ventilation. Both conditions typically present in the newborn period and belong to a group of disorders referred to as neurocristopathies.HD and CCHS most commonly exist as discrete entities, but the coexistence of them is now called Haddad syndrome. Although few documented cases of Haddad syndrome exist in the literature, the association of CCHS and HD suggests a common etiology involving neural crest development.

Download Full-text