Woodhouse–Sakati Syndrome: First report of a Portuguese case

Abstract

Woodhouse-Sakati Syndrome is a very rare autosomal recessive disorder caused by pathogenic variants in the DCAF17 gene, which encodes DDB1-and CUL4-associated factor 17. It is a multisystemic disorder characterized by hypogonadism, adolescent-to young adult-onset diabetes mellitus, hypothyroidism, and alopecia. Neurologic involvement includes childhood-onset moderate bilateral sensorineural hearing loss, mild intellectual disability adolescent-to young adult-onset of extrapyramidal findings, dysarthria, and dysphagia. Brain imaging typically reveals iron deposition in the globus pallidus and periventricular leukodystrophy. We report the case of a 31-year-old Portuguese female, the only child of a consanguineous couple. She presented with cognitive impairment, spastic paraparesis, lower limb dystonia, dysarthria, and dysphagia. She also had hypergonadotrophic hypogonadism associated with primary amenorrhea, insulin-dependent diabetes mellitus with retinopathy, primary hypothyroidism, moderate bilateral sensorineural hearing loss, and alopecia. Serial brain magnetic resonance imaging showed a progressive periventricular leukodystrophy with pontine involvement and significant bilateral iron deposition in the globus pallidus, substantia nigra, and red nucleus.

Case Report: A Deletion Variant in the DCAF17 Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family

“…Some cases have also been recognized in other areas, such as in Europe, Turkey, India, Pakistan, Portugal, France, and Japan. In 2008, DCAF17, which is located on chromosome 2q31.1, was discovered as the causal gene for WSS by Woodhouse and Sakati (Sheridan et al, 2015;Hdiji et al, 2016;Louro et al, 2019;Sendur et al, 2019;Shah et al, 2020). According to the HGMD database, so far 24 mutations in DCAF17 have been reported in the literature, and 18 are responsible for WSS, as listed in Supplementary Table S1.…”

Endocrine Abnormalities in a Case of Neurodegeneration with Brain Iron Accumulation

“…Other features are nonenhancing frontoparietal and periventricular white matter changes that can help distinguish WSS from other NBIAs. 1,2 WSS is not the only NBIA associated with endocrinopathy. Aceruloplasminemia is a form of NBIA characterized by DM and a wide range of neurological symptoms.…”

“…1,2 WSS belongs to the NBIA family, comprising a diverse and heterogenous category of diseases identified with excessive brain (mainly basal ganglia) iron accumulation. 1 The endocrine system is affected in virtually all patients with WSS. 3 The most common findings are hypogonadotropic hypogonadism, alopecia, DM, and primary hypothyroidism.…”

“…3 The most common findings are hypogonadotropic hypogonadism, alopecia, DM, and primary hypothyroidism. 1 Involvement of the neurological system happens in more than half of the patients, with extrapyramidal symptoms, intellectual disability, and sensory neural hearing loss being most commonly reported. 3,4 Parkinsonism and dystonia are the main extrapyramidal manifestations.…”

“…3,4 Parkinsonism and dystonia are the main extrapyramidal manifestations. 1 Seizure is an uncommon manifestation of WSS. 4 Brain MRI demonstrates a small pituitary gland and bilateral hypointensity in globus pallidus on T2 and fluid attenuated inversion recovery sequences indicating iron deposition.…”