Carey-Fineman-Ziter syndrome (CFZS) is a rare congenital myopathy, a term for muscle disorders present from birth. The syndrome primarily impacts the development and function of muscles throughout the body, leading to a variety of physical characteristics.
Core Physical and Developmental Characteristics
The most recognizable signs of Carey-Fineman-Ziter syndrome involve the face and head. Many individuals are born with the Moebius sequence, characterized by weakness or paralysis of the facial muscles. This can result in limited facial expression, an inability to move the eyes from side to side, drooping eyelids, and downward-slanting eye openings.
These facial features are often accompanied by the Pierre Robin sequence, a combination of a small lower jaw (micrognathia), the tongue falling back in the throat (glossoptosis), and a cleft palate. The small jaw can contribute to breathing and swallowing difficulties, particularly in infancy. The skull shape may also appear abnormal, being either larger or smaller than is typical.
A defining characteristic is widespread low muscle tone (hypotonia), which makes an infant seem “floppy” at birth. This underlying muscle weakness affects the entire body, causing delays in motor milestones like sitting, crawling, and walking. Over time, the weakness can lead to skeletal complications, including a curved spine (scoliosis) or inward-turned feet (clubfoot).
The combination of facial muscle weakness and hypotonia creates challenges from birth. Developmental delays are primarily physical, though the degree of impact can vary among individuals. Difficulties with sucking and swallowing are common and can lead to feeding problems that require careful management.
Genetic Origins of the Syndrome
CFZS is caused by mutations in the MYMK gene, which provides instructions for making the myomaker protein. This protein is located on the surface of muscle stem cells (myoblasts) and enables them to fuse together to build long muscle fibers. When MYMK mutations prevent this protein from working correctly, myoblast fusion fails. This disruption in muscle fiber formation is the underlying cause of the congenital myopathy and widespread muscle weakness seen in the syndrome.
The condition is inherited in an autosomal recessive pattern, meaning an affected child must inherit two mutated copies of the MYMK gene—one from each parent. Parents who each have one mutated copy are carriers but do not show signs of the syndrome. When both parents are carriers, there is a 25% chance with each pregnancy that their child will have CFZS.
The Diagnostic Process
Diagnosis often begins with a clinical evaluation at birth. A pediatrician or neurologist will recognize the distinct combination of physical traits, including features of Moebius sequence and Pierre Robin sequence. The presence of widespread hypotonia (“floppy” muscle tone) is another indicator that points toward a congenital myopathy.
Because the symptoms of CFZS overlap with other rare conditions like isolated Moebius syndrome, a differential diagnosis is necessary to rule out other possibilities. Brain imaging, such as an MRI, may be used to look for structural brain anomalies that have been reported in some individuals with the syndrome.
The definitive method for confirmation is molecular genetic testing to sequence the MYMK gene. Identifying mutations in both copies of the gene provides a conclusive diagnosis, distinguishing CFZS from other disorders. This genetic confirmation also allows for accurate family counseling about the condition and its inheritance pattern.
Symptom Management and Care
There is no cure for Carey-Fineman-Ziter syndrome, so management focuses on addressing symptoms through supportive care. This approach requires a coordinated, multidisciplinary team of specialists, including pediatricians, neurologists, surgeons, and therapists. Together, they create a comprehensive care plan to manage the individual’s complex needs.
Physical and occupational therapies are primary treatments. Physical therapy aims to improve muscle strength, balance, and motor skills. Occupational therapy helps individuals adapt to daily life by focusing on skills for feeding and dressing, sometimes using assistive devices to promote independence.
Speech therapy begins in infancy to address feeding and swallowing difficulties caused by facial muscle weakness. Therapists may recommend specialized bottles or feeding tubes to ensure proper nutrition. As a child grows, this therapy also supports language development. Surgical interventions may be necessary to correct physical issues such as a cleft palate or clubfoot.
Long-Term Outlook
The long-term outlook for individuals with CFZS varies depending on the severity of symptoms. The condition is considered non-progressive, meaning the muscle weakness present at birth does not worsen over time. The challenges are developmental rather than degenerative.
The syndrome does not affect cognitive function, and intelligence is within the normal range. The primary health concerns relate to the initial symptoms, such as respiratory difficulties from muscle weakness or feeding problems.
Supportive care helps individuals achieve developmental milestones and lead fulfilling lives. Long-term management focuses on maximizing physical function, preventing complications like breathing problems from scoliosis, and supporting daily activities. Life expectancy can be impacted, particularly for those with severe respiratory issues.