Arnold-Chiari Type I malformation (CMI) is a congenital malformation of unknown incidence. It occurs in a small posterior fossa and constitutes 3–5 mm herniation of the cerebellar tonsils into the spinal canal.1 In all, 25% of patients have cerebrospinal fluid displacement into the spinal cord canal, causing syringomyelia.1, 2
Familial clustering of CMI with and without syringomyelia has been documented in American scientific literature but this case of siblings appears to be the first instance reported in the UK.
Case 1: A 49-year-old gentleman presented to ophthalmic outpatients in 1996 with an 8-month history of horizontal diplopia, vertigo, left arm and thigh pain, a change in gait, and occipital headaches. The patient smoked 20 cigarettes/day, but there was no past medical and, at that stage, no known family history.
Snellen acuity was 6/9 right (amblyopia), 6/6 left. Examination demonstrated a small right esotropia with limited abduction of the right eye. Horizontal nystagmus with a vertical component on right gaze, and reduced convergence were present. There was no sign of optic nerve dysfunction. Humphrey visual fields were full. Intraocular pressures were 15 bilaterally and fundoscopy was normal.
Neurological examination demonstrated broad-based gait and a positive Rhomberg's test. Tone and reflexes were normal.
Routine blood tests and vitamin B12 and folate levels were normal, and VDRL/TPHA screen was negative. Initial MRI scan was normal and differential diagnoses were scan-negative demyelinating disease, Arnold–Chiari malformation, basilar invagination, and paraneoplastic syndrome.
In late 1997, the patient developed oscillopsia and had increasing difficulty walking. Ophthalmic examination further revealed downbeat and rotatory nystagmus in all gaze positions.
Repeat MRI in 1997 demonstrated Chiari Type I malformation, the cerebellar tonsils having herniated to the posterior arch of C2 (Figure 1a and b).
The patient underwent foramen magnum decompression in early 1998 with marked symptom resolution. He presented to ophthalmology again in mid-1998 with recurrence of diplopia and had a small right VI nerve palsy on examination. Further MRI showed no recurrence of hindbrain disease. Following extraocular muscle surgery 1 year later, the patient has remained asymptomatic.
Case 2: Aged 52 years, the elder sister of the aforementioned patient presented to neurologists in 1995 with intermittent shaking and weakness of the left hand. She was an asthmatic on bronchodilators; nothing else was significant medically. Neurological examination and CT brain scan were normal, the history was felt to be suggestive of focal motor seizures and the patient was commenced on Phenytoin 100 mg tds.
In 1996, the patient developed left thenar eminence fasciculation and in 1998 described upper limb paraethesiae. Examination revealed hypertonic lower limbs, hyper-reflexia, right extensor plantar response, and decreased pin prick sensation in the C2–C8 distribution. Power remained full throughout.
MRI scan showed extensive syringomyelia, from C1 to the mid-dorsal region with associated Chiari Type I malformation, the cerebellar tonsils having herniated to the arch of C1 (Figure 2a and b).
In early 1999, the patient underwent foramen magnum decompression with good symptom resolution. She later became ataxic and developed an upper limb tremor.
Repeat MRI scan in 2003 demonstrated that despite satisfactory decompression, the caudal end of the syrinx remained. The patient awaits further neurosurgical intervention.
The first reported case of familial CMI was in the United States in 1990, involving siblings aged 18 months and 2 years.3 Speer et al2 demonstrated familial aggregation in a large patient cohort including 28 sibling pairs. Additionally one-fifth of asymptomatic relatives were diagnosed with CMI±syringomyelia following neuroimaging. No cases of isolated syringomyelia were noted, adding weight to the growing belief that the two conditions are part of a continuum. Milhorat et al demonstrated 12% of 364 patients having one close relative with either CMI or syringomyelia.1 Inheritance patterns suggest autosomal dominant transmission,2, 4, 5 although autosomal recessive patterns with reduced penetrance are also reported.1 Concordance has been reported in monozygotic twins and triplets.1, 2 The potential genetic basis is reinforced by the recognised association of several genetic syndromes with CMI, including many of skeletal abnormality, such as achondroplasia.1, 2
CMI is thought to be a skeletal mesodermal disorder resulting from faulty division embryonic somites forming the skull base and cranoicervical junction.2 Governing this process is the gene Pax-1, whose malfunction causes vertebral fusion and a small posterior cranial fossa.2 Altered cerebrospinal fluid flow in this constricted environment produces the varied symptoms, the commonest being suboccipital headache. Ophthalmic symptoms occur in the majority of patients and include retro orbital pain, floaters, photopsia, photophobia, diplopia, and visual field loss. Hearing loss and vestibular impairment causing vertigo, oscillopsia, and nystagmus, as well as symptoms of spinal cord dysfunction, are prevalent.4
Extensive literature search has failed to identify another reported case of familial CMI in the United Kingdom. Learning points illustrated herein include the diagnostic challenges posed by CMI, and the importance of assessing family history to increase surveillance of potentially affected relatives.
Milhorat TH, Chou MW, Trinidad EM, Kula RW, Mandell M, Wolpert CM et al. Chiari I malformation redefined: clinical, radiographic and genetic features in 364 symptomatic patients. Neurosurgery 1999; 44: 1005–1017.
Speer MC, George TM, Enterline DS, Franklin A, Wolpert CM, Milhorat TH . A genetic hypothesis for Chiari I malformation with or without syringomyelia. Neurosurg Focus 2000; 8(3) Article 12: 1–4.
Herman MD, Cheek WR, Storrs BB . Two siblings with the Chiari I malformation. Pediatr Neurosurg 1990–91; 16: 183–184.
Gimenez-Roldan S, Benito C, Mateo D . Familial communicating syringomyelia. J Neurolog Sci 1978; 36: 135–146.
Gripp KW, Scott Jr CI, Nicholson L, Magram G, Grissom L . Chiari malformation and tonsillar ectopia in twin brothers and father with autosomal dominant spondylo-epiphyseal dysplasia tarda. Skeletal Radiol 1997; 26: 131–133.
We thank the Radiology Department at The Royal Victoria Hospital, Belfast and Dr CS McKinstry for his assistance in interpreting the MRI scans. No funding or proprietary interests. This report has not been published before.
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George, S., Page, A. Familial Arnold-Chiari Type I malformation. Eye 20, 400–402 (2006). https://doi.org/10.1038/sj.eye.6701887
Journal of Neurosurgery (2018)