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Autosomal-recessive syndrome with alopecia, hypogonadism, progressive extra-pyramidal disorder, white matter disease, sensory neural deafness, diabetes mellitus, and low IGF1. Am J Med Genet 143A:149-160

Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 01/2007; 143(2):149-60. DOI: 10.1002/ajmg.a.31497
Source: PubMed

ABSTRACT

We explored the manifestations of an autosomal-recessive multisystemic disorder in several Saudi families. Recognized causes of progressive extra-pyramidal disorder and white matter disease were excluded and the neurological, imaging, endocrine, and skin manifestations of this syndrome described. The onset of these symptoms in these patients began in early adolescence and progressed more rapidly in males. All affected patients had total or partial alopecia, clinical and chemical evidence of hypogonadism (low levels of estradiol and testosterone); females had clear evidence of hypogonadism (streak or absent ovaries), and some patients had diabetes mellitus and/or sensorineural deafness. The constant biochemical abnormality was the low IGF-1. The neurological manifestations included moderate to severe intellectual decline and abnormality of muscle tone and posture with choreo-athetoid and dystonic movements resulting in gait difficulty, dysarthria, difficulty swallowing, and scoliosis. The MRI of brain demonstrated white matter involving cerebellum, brain stem, and cerebral structures, as well as abnormal decreased signal intensity in the basal ganglia with involvement of the substantia nigra. We conclude that the association of hypogonadism, alopecia, and persistent low IGF-1 is a significant autosomal recessive syndrome; it is prevalent in Saudi Arabia. We also demonstrate that the progressive extra-pyramidal disorder, white matter disease, and abnormal signals of the basal ganglia are common features of this syndrome. Sensorineural deafness and diabetes mellitus were recognized features.

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    • "The mutation identified in our patients, a base pair deletion in exon 4 of C2orf37, has been reported in a total of seven families from Saudi Arabia [Alazami et al., 2008], thus likely representing a founder mutation in this region. Al-Semari and Bohlega presented 26 patients with WSS from 12 families in Saudi Arabia [Al-Semari and Bohlega, 2007]. Although these families seem to share the same founder mutation and comprise a fairly genetically homogeneous population, our patients show that variability in clinical presentation exists. "
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    ABSTRACT: Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome [also known as Woodhouse-Sakati syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought.
    Full-text · Article · Nov 2011 · American Journal of Medical Genetics Part A
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    • "We have found novel regulatory genes for cochlear development whose normal expression and activation depends on IGF-I. Severe syndromic deafness in man is associated with null mutations in IGF1 [9], [10], [11] and also with low levels of IGF-I [47]. Accordingly, the Igf1−/− mouse shows poor growth rates, high mortality, profound sensorineural deafness and late postnatal morphological alterations in the cochlea [16] We have shown previously that the absence of IGF-I causes poor myelination and delayed maturation of auditory neurones that suffer apoptosis during the early postnatal mouse development P5-P20 [17], [18]. "
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    ABSTRACT: Insulin-like growth factor-I (IGF-I) provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons. Nevertheless, little is known about the molecular basis of IGF-I activity in hearing and deafness.
    Full-text · Article · Jan 2010 · PLoS ONE
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    ABSTRACT: Woodhouse Sakati syndrome is a rare autosomal recessive neuroendocrine disorder characterized by the combination of alopecia, hypogonadism, diabetes mellitus, mental retardation, sensory neural deafness and extrapyramidal features. Movement disorders mainly consist of dystonia and chorea of the limbs with onset in adolescence. Facial muscles are usually spared, but dysarthria is common. Pyramidal features and peripheral abnormalities are inconsistent features. Most of the reported families are from the Middle Eastern countries although rarely Caucasian cases have been described. Here we present clinical details of two affected siblings from a new Middle East family and draw attention of movement disorder specialists to this entity. We summarize findings from pervious cases with particular focus on neurological and movement disorder features.
    No preview · Article · Mar 2008 · Movement Disorders
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