Expanding on the phenotypic spectrum ofWoodhouse‐Sakatisyndrome due to founder pathogenic variant inDCAF17: Report of 58 additional patients from Qatar and literature review

Abstract

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.

Woodhouse-Sakati Syndrome Presenting With Psychotic Features After Starting Trihexyphenidyl: A Case Report

“…The patient exhibited the classic symptoms of WSS, manifesting with neurological, endocrinological, and ectodermal symptoms as well as laboratory findings [2,3,10,12]. Although it was previously reported that most patients with WSS would present with diabetes mellitus by late teens or early adulthood, the patient only had laboratory findings suggestive of pre-diabetes [3,6,8,9].…”

“…Most of the cases were reported from Saudi Arabia [2,4,5,8]. However, other cases from Asia, the Middle East, and Europe were reported as well: Qatar [9,10], Portugal [11], Tunisia [12], Pakistan [13], India [14], Italy [15] and Turkey [16].…”

Radiological Findings of Woodhouse-Sakati Syndrome: Cases Reported From Saudi Arabia

“…The prevalence of WSS is unknown. However, to date, 180 cases from more than 85 families have been reported in the literature [2].…”

“…People who possess this syndrome have characteristic dysmorphic features such as hypertelorism, triangular face, and prominent nasal bridge. Rarely, cardiac and ophthalmological symptoms may be present [2,[4][5][6]. In a review article of 58 Qatari cases diagnosed with WSS, it was found that all had alopecia as well as hypogonadism, and only 46% had diabetes mellitus [2].…”

“…Most cases reported were from the Middle East, likely related to the consequences of consanguinity. Phenotypic variability of this syndrome, even among siblings, has been observed, adding to the challenges of acquiring a correct diagnosis promptly [2].…”