Boucher-Neuhauser syndrome is an extremely rare disorder, characterized by the triad of ocular abnormalities, spinocerebellar ataxia, and hypogonadotropic hypogonadism. The ocular abnormalities include loss of vision and/or color discrimination, scotoma, retinal degeneration, photophobia, night blindness, and astigmatism. Disturbances in balance, gait and speech, nystagmus, and cerebellar atrophy are the common neurological findings observed in patients with Boucher-Neuhauser syndrome. Patients may also present with dysmetria, frontal headaches, and pes cavus. The endocrinological findings include primary amenorrhea and low LH/FSH levels in females, hypoplastic sexual organs, and sparse secondary sexual hair. The different symptoms have varied ages of onset. The ocular features may occur any time between the first and fourth decades of life, while the endocrine features become evident around puberty. The ataxic features usually manifest themselves in adolescence or early adulthood, but progress slowly.
Mutations in PNPLA6 gene, which encodes a protein named neuropathy target esterase, are identified in patients with Boucher-Neuhauser syndrome. The encoded protein is considered to be involved in differentiation of neurons and neurite outgrowth.
Jbour et al. (2003) described an Arab consanguineous family with three siblings affected with a variant of Boucher-Neuhauser syndrome. The proband was a 21-year old male (karyotypically 46XY), with height and weight below the 5th centile. He developed a slowly progressive ataxic gait at the age of 6-years. Upon examination, he had a mild non-progressive ptosis, a wide based gait, infantile penis, small testes, and sparse pubic hair, along with a mild impairment of cognitive function. Neurologically, he was seen to have normal muscle bulk, but generalized hypotonia, with dyspetria, past pointing, dysdiodochokinesia, and bilateral intentional tremors. Color vision and papillary reactions were normal. There was no involvement of the choroids. The patient had astigmatism, and a posterior pole pigmentary retinopathy was detected. A cone rod dysfunction was also evident in the electroretinogram. Brain MRI showed cerebellar atrophy, normal vermis, and dilatation of the sulci and subarachnoid spaces. The radiological bone age was found to be delayed. Blood test revealed a normal neutrophil count, but with 24% of the neutrophils containing five or more nuclear segments. His two affected younger sisters were of ages 17 and 14 years. Both had onset of ataxia similar to their brother. Height and weight were below the 5th centile. Breast buds and pubic hair were pre-pubertal without menarche. Ophthalmologic examination and brain MRI revealed similar results as the elder brother. They also showed hypersegmentation of the neutrophils. LHRH stimulation test revealed a low baseline LH and FSH without response. All patients had partial anterior pituitary dysfunction, which led to a growth hormone deficiency and resulted in a short stature. Jbour et al. (2003) listed a number of features that differentiated the features of these patients from those of a classic case of Boucher-Neuhauser syndrome. These included the purely cerebellar nature of the ataxia, earlier age of onset of ataxia, lack of involvement of the choroids, and hypersegmentation of the neutrophils. Jbour et al. (2003) suggested that the patients were probably exhibiting a new variant of the syndrome, or could in fact even be exhibiting a new syndrome. The parents of the patients were normal, as were three other children born to them. There was also mention of other relatives having similar disorders. However, they were not available for examination.