Hemifacial Atrophy, Progressive

Clinical Features

This syndrome, originally described by Parry (1825) and Henoch and Romberg (1846), consists of slowly progressive atrophy of the soft tissues of essentially half the face, accompanied usually by contralateral Jacksonian epilepsy, trigeminal neuralgia, and changes in the eyes and hair (Walsh, 1939; Wartenberg, 1945).

Lewkonia and Lowry (1983) reported the case of a 16-year-old boy who developed facial changes at age 7 and had localized scleroderma on one leg and the trunk. The presence of antinuclear antibodies in his serum suggested that the Parry-Romberg syndrome may be a form of localized scleroderma. A review of the literature did not support autosomal dominant inheritance. Lakhani and David (1984) also reported the concurrence of HFA and localized scleroderma. Adebajo et al. (1992) described scleroderma and HFA in association with anti-double-stranded DNA antibodies.

Larner and Bennison (1993) reported discordance in a pair of monozygotic twins. The affected twin was a 23-year-old left-handed white male who complained of progressive wasting of the right side of his face, first noted at age 17. While the patient was left-handed, his twin was right-handed. There was no bony asymmetry in the skull and facial radiographs and no cerebral asymmetry on CT brain scan. Monozygosity was established by DNA fingerprints.

Dupont et al. (1997) reported 4 patients who developed progressive facial hemiatrophy in the first or second decade and later had partial or generalized seizures. Three patients had prominent auras. Brain MRI in all patients showed cortical dysgenesis, ipsilateral to the facial hemiatrophy, consisting of cortex thickening, gyral effacement, and blurring of the white-gray interface. Serum antinuclear autoantibodies were positive in 2 patients and negative in 2 patients. Dupont et al. (1997) concluded that these findings were consistent with a congenital defect of cerebral dysgenesis involving 1 side of the rostral neural tube. The immunologic abnormalities were thought to be secondary to tissue damage.

Shah et al. (2003) reported a 7-year-old child with Parry-Romberg syndrome with severe refractory epilepsy, known as epilepsia partialis continua, requiring hemispherectomy. He had generalized tonic-clonic seizures as well as left facial twitching, clonic activity of the left side of the body, and left facial atrophy and weakness. Brain MRI showed atrophy of the right frontal and parietal lobes. Neuropathologic analysis demonstrated encephalitis with cortical destructive lesions and lymphocytic infiltration of T cells. There were also microglial nodules and gliosis, all consistent with a diagnosis of Rasmussen encephalitis (see 305915 for a discussion of a possible association between Rasmussen encephalitis GRIA3 autoantibodies). Shah et al. (2003) postulated that Parry-Romberg syndrome may share a common autoimmune etiology and pathology with Rasmussen encephalitis.

Anderson et al. (2005) reported 2 first cousins with Parry-Romberg disease, whose fathers were dizygotic twins and whose mothers were sisters. At age 9, the male cousin developed a pale lesion on his left cheek, which was associated with muscle weakness of the adjacent left lip and anesthesia of the top lip; progression of atrophy of the left cheek led to the diagnosis of Parry-Romberg disease at age 14. Examination at age 16 revealed soft tissue wasting with disturbance of dentition producing an upward occlusal cant. His 14-year-old female cousin was noted to have developed a depression on her right forehead which extended into her neck; over the following 2 years, her face became increasingly asymmetric. Examination at age 16 revealed a 'coup de sabre' deformity with thinning of the skin and fat of the right cheek. Her hair at the right temple was thin, and she had right-sided hypoplasia of the maxilla and mandible producing malocclusion with an occlusal cant. Both patients suffered from migraine headaches, and both had eosinophilia. The female cousin was positive for antinuclear factor.

Carreno et al. (2007) reported a patient with HFA who developed recurrent, refractory generalized seizures at age 3 years. By age 5 years, she had progressive right hemiparesis, cognitive decline, and atrophy of the left face. Brain MRI showed marked progressive atrophy of the left hemisphere. At age 11 years, she underwent functional hemispherectomy. Neuropathologic studies showed extensive neuronal loss, astrogliosis, and moderate lymphocytic inflammation. A second unrelated 18-year-old patient presented with linear scleroderma coup de sabre involving the right frontoparietal area and left hemidystonia. Brain MRI showed right hemisphere atrophy. Clonic localized seizures of the left limbs developed at age 23 years. Seizures were progressive, and he ultimately had functional hemispherectomy. There was focal brain necrosis and active inflammation with microglial nodules. Serum studies revealed no autoantibodies and no infectious agents. Carreno et al. (2007) noted that the clinical features in these 2 patients resembled Rasmussen encephalitis, and suggested an immunologic etiology. However, Echenne and Sebire (2007) noted that there is no conclusive evidence to support an immunologic basis for Parry-Romberg syndrome and cautioned against the use of immunosuppressive therapy in such patients.