To examine the historical evolution and expansion of syndromes that constitute hypogonadism, alopecia and neurological involvement as a core feature. 

Childhood onset alopecia associated with neurological and endocrine manifestations represents rare and expanding heterogenous group of neurodegenerative disorders. In the past 4 decades, different phenotype and genetic variants have been reported in the literature.  

A formal literature review was conducted in English using using PubMed and Google Scholar with the terms hypogonadism, alopecia and neurological signs (sensorineural hearing loss and extrapyramidal signs).

Bjornstad (1965) was the first to comment on this association. He reported 8 cases of pili torti, among of which, 5 had sensneural hearing loss, and non-were reported to have hypogonadism or other neurological manifestations. Crandall (1973) described 3 male siblings who similarly had neurosensory deafness, alopecia due to pili torti in addition to secondary hypogonadism. On the contrary, Salti and Salem (1979) reported 3 siblings who did not have hearing loss but did have hypogonadism and alopecia. In 1983, Woodhouse and Sakati (WSS) described similar syndrome but with distinctive facial features. Al-Awadi (1985), Oerter (1992) and Hannig (1995) have reported similar combination of signs. Devriendt (1996) reported similar association with the addition of extrapyramidal movement disorder. Further reporting of WSS have addressed the association of extrapyramidal signs as well. All reported cases have an autosomal recessive inheritance. Genetic variants, however, are rather broad. nine variant mutations in the DCAF17 gene in WSS have been reported. Mutations in the BCS1L gene were linked to Bjornstad syndrome (Hinson; 2007), with 2 variants being discovered so far.

The association of hypogonadism, alopecia and neurological involvement represent a wide heterogenous disorders on both genetic and phenotypic basis. While the discovery of mutational variants for all described syndromes have been expanding, the underlining pathogenesis for such association remains unclear.