ß 2006 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 143A:114–118 (2007) New Syndrome Obesity, Hypothyroidism, Craniosynostosis, Cardiac Hypertrophy, Colitis, and Developmental Delay: A Novel Syndrome Tiong Yang Tan 1,2 * and David J. Amor 1,2 1 Genetic Health Services Victoria, Royal Children’s Hospital, Melbourne, Australia 2 Murdoch Children’s Research Institute, Melbourne, Australia Received 17 June 2006; Accepted 29 September 2006 We describe in two brothers an apparently novel syndrome comprising obesity, congenital hypothyroidism, neonatal colitis, cardiac biventricular hypertrophy, craniosynostosis, and developmental delay. The first brother presented with neonatal colitis and congenital hypothyroidism and died at age 5 weeks of fulminant colitis. The second brother presented neonatally with the same condition, but survived and subsequently developed severe obesity, sagittal and coronal synostosis, and developmental delay. Both preg- nancies had been complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Exhaustive genetic and metabolic investigations have failed to provide a unifying pathogenesis. This unique combination of manifes- tations appears to represent a new syndrome with probable autosomal recessive or X-linked recessive inheritance. ß 2006 Wiley-Liss, Inc. Key words: obesity; hypothyroidism; craniosynostosis; cardiac hypertrophy; colitis; developmental delay How to cite this article: Tan TY, Amor DJ. 2007. Obesity, hypothyroidism, craniosynostosis, cardiac hypertrophy, colitis, and developmental delay: A novel syndrome. Am J Med Genet Part A 143A:114 –118. INTRODUCTION The identification of an apparently novel syn- drome involves careful delineation of the phenotype and thorough literature search. The combination of certain phenotypic manifestations, such as massive early obesity, craniosynostosis, colitis, hypothyroid- ism, and cardiac hypertrophy are useful search terms to use, as they are either objective or reported in only a small number of syndromes. Taken together, they represent an apparently unique combination that we report here. PATIENT 1 The first child born to healthy non-consangui- neous Caucasian parents was delivered at 34 weeks of gestation by emergency Caesarean for severe pre- eclampsia, maternal HELLP (hemolysis, elevated liver function tests, low platelets) syndrome and breech presentation. Birth weight was 2,060 g (25- 50th centile); length and head circumference were not recorded. Ventilatory support was required for 6 days because of respiratory distress. A Guthrie card blood sample taken on Day 4 of life for newborn screening showed a borderline elevated TSH level of 15.8 mU/L (normal less than 13 mU/L). At age 4 weeks thyroid function studies showed a TSH level of 42.8 mU/L and a free T4 level of 7.2 pmol/L (lower limit of range 10 pmol/L), consistent with primary hypothyroidism. Thyroxine treatment was com- menced. A thyroid scan showed a normally placed thyroid gland with radio-isotope uptake in the lower normal range. At age 12 days, he was lethargic, had temperature instability, and non-bilious vomiting. Investigations showed no evidence of infection. This episode resolved after treatment with intravenous fluids, antibiotics, and reduced oral intake. At age 4 weeks, he had non-bilious vomiting, temperature instability, oxygen desaturations, and mottled skin, which settled over 3 days with intravenous antibiotics. He *Correspondence to: Dr. Tiong Yang Tan, Fellow in Clinical Genetics, Genetic Health Services Victoria, 10th Floor Royal Children’s Hospital, Flemington Rd, Parkville VIC 3052, Australia. E-mail: tiong.tan@ghsv.org.au DOI 10.1002/ajmg.a.31548