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Defining the clinical phenotype of Saul-Wilson syndrome.

ABSTRACT: PURPOSE:Four patients with Saul-Wilson syndrome were reported between 1982 and 1994, but no additional individuals were described until 2018, when the molecular etiology of the disease was elucidated. Hence, the clinical phenotype of the disease remains poorly defined. We address this shortcoming by providing a detailed characterization of its phenotype. METHODS:Retrospective chart reviews were performed and primary radiographs assessed for all 14 individuals. Four individuals underwent detailed ophthalmologic examination by the same physician. Two individuals underwent gynecologic evaluation. Z-scores for height, weight, head circumference and body mass index were calculated at different ages. RESULTS:All patients exhibited short stature, with sharp decline from the mean within the first months of life, and a final height Z-score between -4 and -8.5 standard deviations. The facial and radiographic features evolved over time. Intermittent neutropenia was frequently observed. Novel findings included elevation of liver transaminases, skeletal fragility, rod-cone dystrophy, and cystic macular changes. CONCLUSIONS:Saul-Wilson syndrome presents a remarkably uniform phenotype, and the comprehensive description of our cohort allows for improved understanding of the long-term morbidity of the condition, establishment of follow-up recommendations for affected individuals, and documentation of the natural history into adulthood for comparison with treated patients, when therapeutics become available.

SUBMITTER: Ferreira CR

PROVIDER: S-EPMC7205587 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Defining the clinical phenotype of Saul-Wilson syndrome.

Ferreira Carlos R CR Zein Wadih M WM Huryn Laryssa A LA Merker Andrea A Berger Seth I SI Wilson William G WG Tiller George E GE Wolfe Lynne A LA Merideth Melissa M Carvalho Daniel R DR Duker Angela L AL Bratke Heiko H Haug Marte Gjøl MG Rohena Luis L Hove Hanne B HB Xia Zhi-Jie ZJ Ng Bobby G BG Freeze Hudson H HH Gabriel Melissa M Russi Alvaro H Serrano AHS Brick Lauren L Kozenko Mariya M Earl Dawn L DL Tham Emma E Nishimura Gen G Phillips John A JA Gahl William A WA Hamid Rizwan R Jackson Andrew P AP Grigelioniene Giedre G Bober Michael B MB

Genetics in medicine : official journal of the American College of Medical Genetics 20200117 5

<h4>Purpose</h4>Four patients with Saul-Wilson syndrome were reported between 1982 and 1994, but no additional individuals were described until 2018, when the molecular etiology of the disease was elucidated. Hence, the clinical phenotype of the disease remains poorly defined. We address this shortcoming by providing a detailed characterization of its phenotype.<h4>Methods</h4>Retrospective chart reviews were performed and primary radiographs assessed for all 14 individuals. Four individuals und ...[more]

PMID: 31949312

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Project description:Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible.

Dataset Information

Defining the clinical phenotype of Saul-Wilson syndrome.

Publications

Defining the clinical phenotype of Saul-Wilson syndrome.

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