Oculodentodigital dysplasia (ODDD) is odd, mainly due to the fact that it is such a rare-occurring disorder. Good thing too, as it is an uncommon genetic disorder that affects multiple tissues. It is however not such a good thing for the one person in the one million population that is affected by this genetic mutation.

The rare-occurring disorder, ODDD

ODDD is caused by a defective version of the GJA1 gene, responsible for the production of connexin43, a protein vital for communication between the body’s cells. It causes abnormalities in the eyes, nose, teeth and digits, with some features making a show at birth while others present themselves with age. It is discovered that 78% of those affected display the features in more than two of these categories.

Later complications may include higher risk for cataracts, iris atrophy and glaucoma. It may also create vulnerabilities for dental cavities and neurological abnormalities. As of now, there are no known cures for ODDD, as it centres around preventing the symptoms. Prognosis is typically poor for ODDD patients, as it is a genetic condition. Less than 1,000 cases of ODDD have been reported in current literature, including the following two.

As archived in National Foundation for Ectodermal Dysplasias (NFED), the 180+ ectodermal dysplasias are recognised and named based on the specific combination of symptoms shown in affected individuals. Source: NFED
As archived in National Foundation for Ectodermal Dysplasias (NFED), the 180+ ectodermal dysplasias are recognised and named based on the specific combination of symptoms shown in affected individuals. Source: NFED


The boy and his eight-year quest for answers

In 2009, a baby boy came into the world, four days overdue but weighing just above 2kg. He was otherwise healthy, but his mother had a nagging feeling that something was not quite right. For one, he seemed to be missing a patch of skin on his head, but was not bleeding in any way. At a few weeks old, he was making strange noises—like a grunt and a scream—in his sleep. He had a floppy windpipe, or laryngomalacia, which acid-blocking medicine thankfully took care of. His weight however, suffered until he was at the bottom of the growth chart at the age of one.

In 2012, wanting answers, the O family sequenced the boy’s genome with a geneticist and it yielded a less than promising diagnosis—problems with the EVC2 gene, which could cause short stature, nail and teeth problems and serious heart problems. There were more questions than answer, but it was the only thing they could go by. This diagnosis satisfied them, until the boy cracked his lip in the winter and it ran all the way up to his nostril, and worse, refused to heal.

After eight years since the boy’s birth, finally there was a plausible explanation when they sought out a different geneticist, who concluded that the boy’s symptoms—a narrow nose with thin nostrils, cone-shaped teeth that were covered in incomplete-formed enamels, bent fingers and hair that was sparse, coarse and dry—were because of ODDD, which the boy had gotten from a de novo mutation.

The O family remains optimistic despite the diagnosis. There is something peaceful about putting the right label to the picture. Apart from anticipating slow-healing injuries, the boy is happy and thriving.

Features of ODDD include small little fingers, scar from separation of 4th and 5th finger syndactyly, with absence of proximal phalanx of the little finger in the right hand. Photo credit: ACNR
Features of ODDD include small little fingers, scar from separation of 4th and 5th finger syndactyly, with absence of proximal phalanx of the little finger in the right hand. Photo credit: ACNR

The woman diagnosed with ODDD from her gait

Meanwhile in 2013, a 50-year-old woman presented complaints about her gait, which started with a limp on the left leg six years past, was also diagnosed with ODDD. Her history revealed that she was born with bilateral partial syndactyly (fusion) of the toes and fingers and complete syndactyly of the fourth and fifth fingers of the left hand, which was later surgically corrected for, but her digits remain small. In addition, her squint was also corrected for in her childhood, but remains mildly convergent in left eye.

Microdontia and enamel hypoplasia. Photo credit: ACNR
Microdontia and enamel hypoplasia. Photo credit: ACNR

Apart from that, her teeth were small and deficient in enamel, whereby she had lost 4 permanent teeth by the age of 24. Growing up, she was prone to frequent diarrhoea, urinary frequency, nocturia and urinary incontinence. She was also the first to present a malformation of the fallopian tubes for ODDD, resulting in primary infertility.

Like the boy from the O family, the woman’s parents or her older brother did not display any abnormalities. She has been said to suffer from a sporadic form of ODDD, affecting multiple tissues including the eyes, nose, teeth, fingers, fallopian tubes and nervous system. The skin on her palms and soles are also thickened. The management of her symptoms and of ODDD patients in general are therefore multidisciplinary, where early recognition of the syndrome could greatly benefit the prevention and treatment. MIMS

Read more:
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Escaping death: ‘New skin’ saves boy with rare condition
Unexplained medical conditions continue to baffle doctors

Sources:
https://www.statnews.com/2017/12/21/fragile-skin-stunted-growth-mystery/
https://ghr.nlm.nih.gov/condition/oculodentodigital-dysplasia
http://www.acnr.co.uk/2013/09/oculo-dento-digital-dysplasia-oddd/
https://www.dovemed.com/diseases-conditions/oculo-dento-digital-dysplasia/
https://www.nfed.org/learn/types/
https://rarediseases.org/rare-diseases/oculo-dento-digital-dysplasia/