What is Miller Syndrome?

Miller syndrome is a very rare genetic disorder that can cause a number of different physical deformities of the face and extremities. Infants who are born with the condition may have very small lower jaws, eye and ear abnormalities, missing fingers or toes, and other irregular features. In severe cases, major health complications such as hearing loss and breathing difficulties can develop. Patients who suffer from Miller syndrome typically need to take medications, undergo multiple surgeries, and participate in ongoing physical therapy to improve their appearances and quality of life.

Genetic researchers have identified a particular gene on chromosome 16 that, when mutated or inactivated, appears to be responsible for Miller syndrome. The DHODH gene normally produces important enzymes that contribute to the development of facial bones, muscles, nerve fibers, and skin cells in the head and neck of an embryo. The enzymes also promote the proper growth of the arms and legs. When the DHODH gene is mutated, it cannot create functional enzymes. Miller syndrome follows an autosomal recessive inheritance pattern, indicating that both parents need to carry mutated copies of the DHODH gene in order for a child to get the condition.

The severity and type of symptoms can vary among infants with Miller syndrome. Most patients have smaller-than-average jaws and poorly developed cheekbones, which may interfere with breathing and swallowing. Cleft palates, or holes in the roof of the mouth, are common as well. The ears may be small and folded over, and the eyes can be slanted toward the nose. Other facial abnormalities can include broad noses, cleft lips, and drooping eyelids.

The most common limb abnormality is the absence of the fifth digits on the hands or feet. Some patients have webbed digits, short forearms, and bowed legs. Other possible defects include extra nipples on the chest and genital abnormalities, such as undescended testicles in male infants. Miller syndrome rarely presents with any neurological symptoms, and most people with the condition are of normal intelligence.

Miller syndrome is usually diagnosed shortly after birth based on an infant's appearance and symptoms. Genetic blood tests can confirm the presence of DHODH abnormalities in the patient and his or her parents. Imaging scans and other diagnostic tests are useful in determining the extent of bone irregularities and whether or not internal organs are affected.

Treatment decisions are made based on the severity of symptoms. Infants with breathing troubles may need to be placed on ventilation machines or fitted with breathing and feeding tubes. Patients who are stable typically do not require major treatment until they are older. Surgeries to correct facial and limb deformities are often performed in late childhood once bones have more fully developed. Patients may need several rounds of surgery and lifelong physical therapy to overcome their physical issues.