BridgeMar Syndrome

BridgeMar Syndrome

A novel infantile spinal muscular atrophy phenotype with additional features

BridgeMar Syndrome
BridgeMar Syndrome is a unique and severe neurodegenerative disorder first observed in affected sisters by Dr. John Optiz. The genetic etiology of BridgeMar Syndrome remains unknown, but autosomal recessive inheritance is suspected. Parents are nonconsanguinous (unrelated) and have one unaffected child, a son. Although we suspect the disorder is inherited, the exact cause of the disorder remains unknown.

By posting this information about BridgeMar Syndrome we hope to increase awareness of this disorder to determine whether there are other families who may have similarly affected children. We hope that identifying additional cases will help clarify the cause of this devastating disorder.


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Key Clinical Characteristics

  • Congenital microcephaly (small head size at birth) with evidence of subsequent poor brain growth and progressive atrophy
  • Leukodystrophy (paucity of central brain myelin with progressive myelin loss)
  • Progressive neuromuscular weakness evolving in early infancy, resulting in lower extremity paralysis (severe weakness progressing to complete leg paralysis)
  • Intercostal weakness (weakness of the respiratory muscles)
  • Bulbar dysfunction (loss of ability to protect the airway with feeding) and tongue fasiculations (indicating involving of nerve cells innervating the tongue)
  • Autonomic dysregulation:
    • Ptosis (droopy eyelids)
    • Bowel dysmotility (abnormal movement of food through the stomach, small and large intestines, with bowel distention, poor gastric emptying and constipation)
    • Gastroesophageal reflux (reflux of stomach contents into the esophagus, increasing risk for aspiration into the lungs)
    • Vascular instability (poor blood flow manifest by cool extremities, color change involving the extremities and trunk, skin mottling)
    • Abnormal sweating
    • Temperature dysregulation (difficulty controlling body temperature)
    • Apneic episodes (sudden spells in which the baby stops breathing)
  • Cataracts: posterior subcapsular cataracts, in one case congenital and in the other developing within the first few months of life

Additional features

  • Sensorineural deafness
  • Abnormal visual behavior consistent with cortical visual impairment
  • Global neurodevelopmental impairment
  • Partial agenesis of the corpus callosum
  • Scoliosis, in one case associated with thoracic hemivertebrae
  • Neurogenic bladder
  • 11 pairs of ribs
  • Recurrent rigors, high fevers of uncertain etiology up to 106 degrees Fahrenheit
  • Early in the clinical course, spasticity may be present in the setting of absence of deep tendon reflexes


Bridget - 4 months old

Of the sisters diagnosed by Optiz (mentioned above), the first sister died at one year of age of respiratory failure, after suffering progressive weakness and respiratory insufficiency over many months. The second sister developed seizures around four months of age. She was given treatment with L-dopa/carbidopa and BH4 (tetrahydrobiopterin) for low cerebrospinal fluid levels of BH4 and HVA (a dopamine metabolite) and had some clinical response characterized by improved ptosis, level of alertness and circulatory instability. However, she continued to decline over time, and ultimately died at 19 months of age with acute respiratory distress syndrome in association with an influenza infection.

Identification of similarly affected infants could help to further clarify the genetic and pathophysiologic basis of this disorder.


Brain MRI

The following are some diagnostic studies we conduct and the characteristics they reveal. Brain MRI indicates a diffuse decrease in myelin (white matter) but also widespread brain atrophy (loss of nerve cell bodies or grey matter). Decreased myelin formation and evidence of progressive myelin loss occurs over time (myelin, or white matter, is the substance that surrounds nerve cells and helps them conduct electrical signals faster and more efficiently; one general term for brain disorders that involve these kind of changes is leukodystrophy).

  • EMG (electromyography: a special test used to help determine the cause of the weakness) shows that the weakness is most consistent with anterior horn cell disease or a motor predominant neuronopathy. Anterior horn cells are the cells in the spinal cord that send out the nerve fibers to the muscles to make them work properly.
  • Muscle and nerve biopsy studies reveal findings indistinguishable from those seen in 5q SMA: neurogenic atrophy.
  • Metabolic evaluation excluded hexosaminidase deficiency, serine deficiency, peroxisomal and mitochondrial dysfunction.
  • Cerebrospinal fluid analysis (CSF) for neurotransmitter metabolites in one sibling revealed evidence of tetrahydrobiopterin (BH4) deficiency and decreased homovanillic acid (HVA) consistent with a central nervous system dopamine deficiency state. It is unclear whether these abnormalities are primary or secondary.

Please contact our clinical coordinators at (801) 585-9717 if your child is similarly affected, to inquire about participating in research studies to help us better understand this complex disorder.