Mar 17, 2023

Early in life, the participant began to show signs of motor and developmental delay. At 3 years old, she started having absence seizures and has also had generalized tonic-clonic seizures. Her motor development has been quite slow. She has significant muscle weakness, low muscle tone in her face and trunk (facial and axial hypotonia), high muscle tone and involuntary muscle contractions in her arms and legs (appendicular hypertonia and dystonia of extremities), and intermittent twisted neck (cervical torticollis). She walks with a gait trainer and does not roll or sit independently.

At age 10 she remains non-verbal but is able to speak in complete sentences using an eye gaze communication device. She reads at approximately a second-grade level.  She has had recurrent episodes of increased activated immune cells (hemophagocytic lymphohistiocytosis). In addition, she had a ruptured brain aneurysm at age 10.

• Absence seizures
• Generalized tonic-clonic seizures
• Abnormal brain activity (EEG abnormality)
• Brain damage (abnormality of the cerebral white matter, cerebral and cerebellar volume loss)
• Absent speech
• Muscle weakness (severe generalized muscle weakness, tetraparesis)
• Decreased muscle tone of face and trunk (facial and truncal hypotonia)
• Increased muscle tone of arms and legs (lower and upper limb hypertonia)
• Urinary retention
• Motor delay (gross and fine motor delay)
• Limb dystonia (involuntary muscle contractions)
• Slow movements (bradykinesia)
• Abnormal inner ear formation (abnormality of the internal auditory canal, hypoplasia of the inner ear)
• Hearing loss (congenital right-sided severe sensorineural hearing loss)
• Abnormal facial features (frontal bossing, prominent forehead, slight facial asymmetry, full cheeks, thick upper lip vermilion, anteverted nares, telecanthus, microdontia, widely spaced teeth, short nose, depressed nasal bridge, high anterior hairline, hyperplasia of midface, deeply set eyes, ptosis, intermittent exotropia)
• Flattened base of the skull (platybasia)
• Indentation of the skin on the lower back (sacral dimple)
• Vascular abnormalities (bilateral cutis marmorata of the lower extremities, prominent veins on trunk, developmental venous anomaly)
• Ruptured brain aneurysm
• Heart structure abnormality (abnormal aortic morphology)
• Twisted neck (intermittent cervical torticollis)
• Skeletal abnormalities of the hip (flared iliac wings, flat acetabular roof, bilateral coxa valga)
• Increased activated immune cells diagnosed and treated at age 3 and 6 (hemophagocytic lymphohistiocytosis)

• Depakote – seizures
• Sinemet – movement and tone disorder

• Etoposide and dexamethasone – hemophagocytic lymphohistiocytosis at age 3