New genetic disorder named for Children's Hospital of Philadelphia team

An authoritative reference site for genetic diseases, Online Mendelian Inheritance in Man (OMIM), now designates this condition as Mulchandani-Bhoj-Conlin syndrome (MBCS), characterized by failure to thrive, severe short stature and profound feeding difficulties, caused by an abnormality of chromosome 20.

MBCS is an imprinting disorder. Normally, people inherit one copy of each chromosome from each parent. However, children with MBCS have both copies of chromosome 20 from their mother, and none from their father. While the exact cause of MBCS is unknown, the researchers predict that the disorder is caused by the lack of paternally inherited genes on chromosome 20.

Surabhi Mulchandani, MS; Elizabeth Bhoj, MD, PhD, and Laura Conlin, PhD, co-led a multi-center effort that resulted in a scientific article on the syndrome, published in 2015. The research involved patients and clinicians from CHOP, A.I. duPont Hospital for Children, Stanford University, and centers in Germany and the UK. Conlin and Mulchandani are a Director and Manager, respectively, of the Genomics Diagnostics Laboratory in CHOP's Division of Genomic Diagnostics, while Bhoj is a clinician-researcher in CHOP's Division of Human Genetics.

In their research article, the co-authors reported on eight children diagnosed with the syndrome. All were very small at or before birth, and six had severe feeding problems that required tube feeding in first few years of life. Some of the patients received human growth hormone treatments, which were safe and effective. Except for one infant, the patients ranged from 4 to 12 years of age when the study occurred. They did not have major developmental delays and all were in mainstream schools working at grade level.

Before the cause of their symptoms was identified, the children and families experienced long "diagnostic odysseys." The authors suggest that infants with unexplained severe growth failure should receive specialized diagnostic testing that can identify this syndrome and allow for early intervention and treatment. The study team also expects that more children will be identified with MBCS as knowledge of the syndrome spreads to healthcare providers.

"The staggering improvements in diagnosis of genetic disorders over the past two decades have led to greatly improved diagnostic rates, and to many discoveries, such as the identification of the newly described Mulchandani-Bhoj-Conlin syndrome," said Nancy B. Spinner, PhD, chief of the Division of Genomic Diagnostics at CHOP. "We are so proud to be a part of helping families of children find answers, which we hope will lead to improved care, a better understanding of disease mechanisms, and eventual treatments."