NIH: Researchers at the National Eye Institute (NEI), part of the National Institutes of Health, have identified the genetic underpinnings of a rare disorder that causes children to be born with deafness, blindness, albinism and fragile bones. The newly recognized syndrome, COMMAD, affects children who inherit two mutations of a gene – one from each parent – each of whom is deaf due to another rare, genetic disorder called Waardenburg syndrome 2A. A paper documenting the first recognized cases of COMMAD appears in the American Journal of Human Genetics.
The identification of COMMAD and its genetic cause is important
because intermarriage within the deaf community is relatively common,
and people who are deaf may not know that their deafness is associated
with Waardenburg 2A. Prospective parents who are both deaf may want to
consider genetic counseling prior to conceiving a child. Should both
individuals have Waardenburg 2A, they risk passing mutated versions of a
critical gene to their child, resulting in COMMAD, said the paper’s
lead author, Brian P. Brooks, M.D., Ph.D., NEI clinical director and
chief of the Pediatric, Developmental, and
Genetic Ophthalmology Section.
The vast majority of Americans born deaf do not have Waardenburg
syndrome 2A, which, in addition to hearing loss, is associated with
premature graying of the hair, blue eyes, fair skin, and sometimes
vision problems. A comprehensive dilated eye exam may detect eye
abnormalities that suggest the need for genetic testing to rule
out Waardenburg 2A.
Brian P. Brooks, M.D., Ph.D.
In the paper, Brooks describes two unrelated cases of children born
with COMMAD, which stands for coloboma (a condition where normal tissue
in or around the eye is missing), osteopetrosis (abnormally dense bones
that are prone to fracture), microphthalmia (small or abnormally formed
eyes), macrocephaly (abnormal enlargement of the head), albinism (lack
of melanin in the skin, hair, and eyes) and deafness. Both children
described in the paper are blind due to eye malformations. Children with
COMMAD require close supervision, and communicating with them involves
tactile methods such as a hand-touch alphabet.
First author, Aman George, Ph.D.,
of the NEI Intramural Research
The two children in the study had inherited from each parent mutated
versions of a gene called MITF, which stands for
microphthalmia-associated transcription factor. Future research is
needed to understand the role of MITF during early development and how
mutations in this gene result in the development of Waardenburg syndrome
2A, or COMMAD.
The work was supported by the intramural research program of the National Eye Institute.
Reference: George A, Zand DJ, Hufnagel RB, et al. Biallelic Mutations
in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly,
Albinism, and Deafness. Am J Hum Genet. Dec 01 2016;99(6):1388-1394(link
Rare Disease Day®(link is external) takes place worldwide, typically
on or near the last day of February each year, to raise awareness among
policymakers and the public about rare diseases and their impact on
patients’ lives. For more information about events at NIH observing the
day, go to https://ncats.nih.gov/rdd (link is external)(link is external)
NEI leads the federal government's research on the visual system and
eye diseases. NEI supports basic and clinical science programs that
result in the development of sight-saving treatments and address special
needs of people with vision loss. For more information, visit www.nei.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's
medical research agency, includes 27 Institutes and Centers and is a
component of the U.S. Department of Health and Human Services. NIH is
the primary federal agency conducting and supporting basic, clinical,
and translational medical research, and is investigating the causes,
treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit www.nih.gov (link is external).
NIH…Turning Discovery Into Health®