Patterns of neurological manifestations in Woodhouse-Sakati Syndrome

Bohlega, Saeed; Abusrair, Ali; Al-Ajlan, Fahad S.; Alharbi, Nawal; Alsemari, Abdulaziz; Bohlega, Balsam; Abualsaud, Dalya; Alkuraya, Fowzan S.

doi:10.1016/j.parkreldis.2019.10.007

Cited by 21 publications

(37 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Almost half of the cases had NIS of 3–4 (Type 1 WSS) along with severe disability and rapid disease progression, while the other half had NIS of 0–1(Type 2 WSS) and showed either absent or mild neurological involvement with preserved activities of daily living. In addition, neurological symptoms had an earlier mean age of onset in Type 1 WSS (12.6 ± 4.5 years) compared to Type 2 WSS (18.1 ± 4.3 years) and the rate of ID was significantly higher in Type 1 WSS (S. Bohlega et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In a more recent study, S. Bohlega et al (2019) assessed the neurological manifestations of 38 WSS patients with the same founder pathogenic variant c.436delC using the Neurological Impairment Scale (NIS) and delineated two distinct phenotypes. Almost half of the cases had NIS of 3–4 (Type 1 WSS) along with severe disability and rapid disease progression, while the other half had NIS of 0–1(Type 2 WSS) and showed either absent or mild neurological involvement with preserved activities of daily living.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expanding on the phenotypic spectrum of Woodhouse‐Sakati syndrome due to founder pathogenic variant in DCAF17: Report of 58 additional patients from Qatar and literature review

Ali

Al‐Dewik

Mohammed

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Woodhouse‐Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine and ectodermal disorder caused by variants in the DCAF17 gene. In Qatar, the c.436delC variant has been reported as a possible founder pathogenic variant with striking phenotypic heterogeneity. In this retrospective study, we report on the clinical and molecular characteristics of additional 58 additional Qatari patients with WSS and compare them to international counterparts' findings. A total of 58 patients with WSS from 32 consanguineous families were identified. Ectodermal and endocrine (primary hypogonadism) manifestations were the most common presentations (100%), followed by diabetes mellitus (46%) and hypothyroidism (36%). Neurological manifestations were overlapping among patients with intellectual disability (ID) being the most common (75%), followed by sensorineural hearing loss (43%) and both ID and aggressive behavior (10%). Distinctive facial features were noted in all patients and extrapyramidal manifestations were uncommon (8.6%). This study is the largest to date on Qatari patients with WSS and highlights the high incidence and clinical heterogeneity of WSS in Qatar due to a founder variant c.436delC in the DCAF17 gene. Early suspicion of WSS among Qatari patients with hypogonadism and ID, even in the absence of other manifestations, would shorten the diagnostic odyssey, guide early and appropriate management, and avoid potential complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expanding on the phenotypic spectrum of Woodhouse‐Sakati syndrome due to founder pathogenic variant in DCAF17: Report of 58 additional patients from Qatar and literature review

Ali

Al‐Dewik

Mohammed

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Nevertheless, patients can display a marked phenotypic variability. Current treatment is symptomatic/palliative (Bohlega & Alkuraya, ).…”

Section: Our Patient's Clinical Features Compared To Clinically Diagnmentioning

confidence: 99%

Woodhouse–Sakati Syndrome: First report of a Portuguese case

Louro

Durães

Oliveira

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

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.

show abstract

“…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. 1 Seizure is an uncommon manifestation of WSS.…”

mentioning

confidence: 99%

“…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. Other features are nonenhancing frontoparietal and periventricular white matter changes that can help distinguish WSS from other NBIAs.…”

mentioning

confidence: 99%