Hunter-Macdonald Syndrome

Clinical Features

Hunter and MacDonald (1989) described a 21-year-old man with a mild form of epiphyseal dysplasia characterized by disproportionate short stature, congenital camptodactyly, and pulmonic valve stenosis. He was born to nonconsanguineous French Canadian parents at 8.5 months after an uncomplicated pregnancy. His father died shortly after his birth of a brain tumor. Physical examination at age 9 because of speech problems and short stature revealed a height of 114 cm (less than 3rd percentile), pectus carinatum, 2/6 ejection murmur, abnormal hands, and 2-3 toe syndactyly. Radiographs revealed delayed bone age, hypoplastic fifth finger middle phalanges, and pseudoepiphyses of the middle phalanges. Radial epiphyses were small and flattened. On reexamination at age 15, he had high myopia, bilateral conductive hearing loss, scoliosis, and decreased extension at the elbows, hips, and knees. At age 21, he was 157.5 cm tall with an upper-lower segment ratio of 1.02 (+2 SD), confirming short limbs. He had a prominent forehead with bitemporal grooves, midface hypoplasia, and short philtrum. There was fifth finger clinodactyly and lack of distal flexion creases. Hunter and MacDonald (1989) concluded that their patient had a subtle form of multiple epiphyseal dysplasia that spared the hips, with unusual facies, myopia, camptodactyly, and lack of distal flexion finger creases.

Ardinger et al. (1999) described a 3-generation family with Hunter-MacDonald syndrome. The proband was a 7-year-old girl with proportionate short stature. She had a tall forehead, bitemporal narrowing, ptosis, thin upper lip, and short philtrum. Skeletal abnormalities included pectus carinatum, mild PIP camptodactyly, skewed fingers, and severe metatarsus adductus. She had sensorineural hearing loss and congenital heart defects including mitral valve prolapse, bicuspid aortic valve, and mild mitral and aortic regurgitation. The same condition was present in her mother, maternal uncle, maternal grandmother, and possibly the maternal great-grandmother, suggesting autosomal dominant inheritance. The adults had increasing spinal curvature, early degenerative hip disease requiring replacement in the late twenties to early forties, and worsening camptodactyly. Final adult height ranged from 149.9 to 157.5 cm.

Armstrong et al. (2008) provided follow-up on the man first reported by Hunter and MacDonald (1989). Then 36 years old, he had had a series of unexplained, intermittent, transient cranial nerve palsies since the age of 21. MRI performed at age 35 revealed a mass in the subfrontal region which was pathologically confirmed to be a meningothelial meningioma. Review of his father's medical records showed that his death at age 35 was attributed to a meningioma of the pituitary region identified at autopsy. The father had short stature (adult height 160 cm), leading Armstrong et al. (2008) to conclude that the father also had Hunter-MacDonald syndrome. Armstrong et al. (2008) also reevaluated the then 42-year-old mother of the girl described by Ardinger et al. (1999). She had similar craniofacial features and hearing loss as her daughter. In addition, she had significant myopia and esotropia. Because her mother had died at age 55 years of a brain tumor, an MRI was performed and a meningioma was detected. Armstrong et al. (2008) concluded that predisposition to meningioma is a cardinal feature of Hunter-MacDonald syndrome.

Inheritance

The transmission pattern of Hunter-MacDonald syndrome in the family reported by Ardinger et al. (1999) was consistent with autosomal dominant inheritance.