Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Golabi and Rosen (1984) have reported on a new X-linked mental retardation/multiple congenital anomalies (XLMR/MCA) syndrome of pre- and postnatal overgrowth, characteristic "coarse" facial appearance with macrostomia, midline groove of tongue, lower alveolar ridge and lip, submucous cleft of palate, supernumerary nipples, intestinal anomalies, supernumerary pair of ribs, anomalies of sacrum and tailbone, hypoplastic index fingernails, postaxial polydactyly and other digital anomalies. This was an incompletely recessive trait with some manifestations evident in an obligatory carrier. Here we report on a second family (studied at the University of Wisconsin for over 9 years) in which 3 males born to half-sisters and their mother were affected with the Golabi-Rosen syndrome (GRS). Overgrowth was not a prominent manifestation in these affected males. Presence of cystic kidneys, peculiar skin changes and hepatomegaly make it likely that the Golabi-Rosen syndrome is an X-linked MCA/dysplasia/MR syndrome. Its metabolic basis remains unknown. It seems to be an incompletely recessive trait.
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PMID:The Golabi-Rosen syndrome--report of a second family. 653 56

Young-Simpson syndrome is a rare congenital disorder, characterized by congenital hypothyroidism, congenital heart defects, facial dysmorphism, cryptorchidism in males, hypotonia, mental retardation, and postnatal growth retardation. We describe the cases of a 5-year-old boy and a 7-year-old girl with a similar constellation of symptoms and compared them with previously reported patients.
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PMID:Young-Simpson syndrome: further delineation of a distinct syndrome with congenital hypothyroidism, congenital heart defects, facial dysmorphism, and mental retardation. 1021 38

Here, we report the clinical and molecular analysis of 75 patients with overgrowth and mental retardation, including 45 previously reported cases [Rio et al., 2003; Baujat et al., 2004]. Two groups are distinguished: group I corresponding to patients with recognizable overgrowth syndromes (Sotos syndrome (SS), Weaver syndrome (WS), Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome (SGBS), and del(22)(qter) syndrome) (60 cases) and group II corresponding to unclassified cases (15 patients). We investigated NSD1 and GPC3 deletions or mutations, 11p15 abnormalities, and 22qter deletions. Surprisingly, in Group I, two SS patients had 11p15 abnormalities and two patients with Beckwith-Wiedemann syndrome had NSD1 aberrations. In group II, two cases of del(22)(qter) were identified but neither NSD1, 11p15, nor GPC3 abnormalities were detected. These results emphasize the clinical and molecular overlap in overgrowth conditions.
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PMID:Clinical and molecular overlap in overgrowth syndromes. 1601 Jun 74

The Simpson-Golabi-Behmel syndrome (SGBS) (OMIM 312870) is an overgrowth/multiple congenital anomalies syndrome caused by a semi-dominant X-linked gene encoding glypican 3 (GPC3). It shows great clinical variability, ranging from mild forms in carrier females to lethal forms with failure to thrive in males. The most consistent findings in SGBS are pre- and postnatal macrosomia, characteristic facial anomalies and abnormalities affecting the internal organs, skeleton, and on some occasions, mental retardation of variable degree. SGBS is also associated with an increased risk of developing embryonal tumors, mostly Wilms and liver tumors. We describe two molecularly-confirmed families with SGBS. All patients had typical manifestations of SGBS including some female relatives who had minor manifestations of the disorder. Some patients had novel findings such as a deep V-shaped sella turcica and six lumbar vertebrae. Molecular studies in affected patients showed a deletion of exon 6 in family 1 and an intronic mutation in family 2.
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PMID:Clinical and molecular studies on two further families with Simpson-Golabi-Behmel syndrome. 1615 29

This report describes a 14-year-old male with Simpson-Golabi-Behmel overgrowth syndrome. He was born via cesarean section because of macrocephaly and subsequently exhibited significant developmental delay in motor, language, and cognitive skills with mental retardation and epilepsy. He manifests the characteristic dysmorphic ("bulldog") facial features of Simpson-Golabi-Behmel syndrome. His molecular genetic testing has substantiated the clinical diagnosis of Simpson-Golabi-Behmel syndrome; however, he is unique in that he has mental retardation, hydrocephalus, and epilepsy, which have not been previously documented in Simpson-Golabi-Behmel syndrome in the literature.
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PMID:Expanding the clinical picture of Simpson-Golabi-Behmel syndrome. 1645 28

We report on 11 patients from 8 families with a blepharophimosis and mental retardation syndrome (BMRS) phenotype. Using current nosology, five sporadic patients have Ohdo syndrome, associated with congenital hypothyroidism in two of them (thus also compatible with a diagnosis of Young-Simpson syndrome). In two affected sibs with milder phenotype, compensated hypothyroidism was demonstrated. In another family, an affected boy was born to the unaffected sister of a previously reported patient. Finally, in the last sibship, two affected boys in addition had severe microcephaly and neurological anomalies. A definitive clinical and etiologic classification of BMRS is lacking, but closer phenotypic analysis should lead to a more useful appraisal of the BMRS phenotype. We suggest discontinuing the systematic use of the term "Ohdo syndrome" when referring to patients with BMRS. We propose a classification of BMRS into five groups: (1) del(3p) syndrome, (possibly overlooked in older reports); (2) BMRS, Ohdo type, limited to the original patients of Ohdo; (3) BMRS SBBYS (Say-Barber/Biesecker/Young-Simpson) type, with distinctive dysmorphic features and inconstant anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism. BMRS type SBBYS is probably an etiologically heterogeneous phenotype, as AD and apparently AR forms exist; (4) BMRS, MKB (Maat-Kievit-Brunner) type, with coarse, triangular face, which is probably sex-linked; (5) BMRS V (Verloes) type, a probable new type with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia, which is likely autosomal recessive. Types MKB and V are newly described here.
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PMID:Blepharophimosis-mental retardation (BMR) syndromes: A proposed clinical classification of the so-called Ohdo syndrome, and delineation of two new BMR syndromes, one X-linked and one autosomal recessive. 1670 52

We describe a patient with the clinical spectrum of Young-Simpson syndrome. This rare genetic disorder is characterized by congenital hypothyroidism, mental retardation and blepharophimosis. Young-Simpson syndrome is, at present, poorly known to endocrinologists and pediatricians, and should be included in the differential diagnosis of congenital hypothyroidism. It is important to underline that the association of congenital hypothyroidism, blepharophimosis and ptosis allows an exact clinical diagnosis, since the majority of other clinical aspects are common to other disorders.
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PMID:Congenital hypothyroidism in Young-Simpson syndrome. 1918 5

We ascertained a multi-generation Malaysian family with Joubert syndrome (JS). The presence of asymptomatic obligate carrier females suggested an X-linked recessive inheritance pattern. Affected males presented with mental retardation accompanied by postaxial polydactyly and retinitis pigmentosa. Brain MRIs showed the presence of a "molar tooth sign," which classifies this syndrome as classic JS with retinal involvement. Linkage analysis showed linkage to Xpter-Xp22.2 and a maximum LOD score of 2.06 for marker DXS8022. Mutation analysis revealed a frameshift mutation, p.K948NfsX8, in exon 21 of OFD1. In an isolated male with JS, a second frameshift mutation, p.E923KfsX3, in the same exon was identified. OFD1 has previously been associated with oral-facial-digital type 1 (OFD1) syndrome, a male-lethal X-linked dominant condition, and with X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2). In a yeast two-hybrid screen of a retinal cDNA library, we identified OFD1 as an interacting partner of the LCA5-encoded ciliary protein lebercilin. We show that X-linked recessive mutations in OFD1 reduce, but do not eliminate, the interaction with lebercilin, whereas X-linked dominant OFD1 mutations completely abolish binding to lebercilin. In addition, recessive mutations in OFD1 did not affect the pericentriolar localization of the recombinant protein in hTERT-RPE1 cells, whereas this localization was lost for dominant mutations. These findings offer a molecular explanation for the phenotypic spectrum observed for OFD1 mutations; this spectrum now includes OFD1 syndrome, SGBS2, and JS.
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PMID:OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin. 1980 48

Blepharophimosis-mental retardation syndromes (BMRS) include a group of clinically and etiologically heterogeneous conditions, which can occur as isolated features or as part of distinct disorders displaying multiple congenital anomalies. We report on two siblings, a 6-year-old girl and an 18-month-old male, presenting with overlapping clinical findings. Major characteristics included facial dysmorphisms with upward slanted palpebral fissures, blepharophimosis, telecanthus, hypertelorism, posteriorly rotated and abnormal ears, and micrognathia. Ectodermal abnormalities consisted of fine hair, sparse eyebrows, and thin skin. Both patients had feeding difficulties with gastro-esophageal reflux and growth retardation. Psychomotor skills were severely delayed with no verbal capacity. The male sib also displayed low growth hormone (GH) levels, while the older sister had low cholesterol and mildly elevated TSH levels. Numerous metabolic/genetic investigations, including cholesterol precursors, dosage, and high-resolution array-CGH, were negative. BMR syndromes, including Dubowitz syndrome, Marden-Walker syndrome, Ohdo/Ohdo-like syndromes, and the cholesterol storage disorders were considered. We concluded that these two patients are affected by a possible autosomal recessive condition within the heterogeneous clinical spectrum of BMRS, fitting with the Young-Simpson syndrome subtype.
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PMID:The difficult nosology of blepharophimosis-mental retardation syndromes: report on two siblings. 2156 2

Tall stature is usually defined as a height beyond 97th percentile or more than 2 SD above the mean height for age and sex in a defined population. Familiar tall stature, also known as constitutional tall stature, is the most common cause of tall stature. Overnutrition, obesity, also usually causes overgrowth. Tall stature by itself is not a pathological condition, however, there are a number of disorders associated with tall stature. Some genetic disorders and syndromes may be associated with mental retardation and various complications. Therefore, recognition of tall stature and revealing the underlying pathogenic causes and making the diagnosis are important not to miss the serious conditions and to provide adequate medical care and genetic counseling. Pathological causes for tall statute include endocrine disorders, such as excessive growth hormone secretion, hyperthyroidism, precocious puberty and lipodystrophy, chromosome disorders, such as Trisomy X (47, XXX female), Klinefelter syndrome (47, XXY), XYY syndrome (47, XYY male) and Fragile X syndrome, and syndromes and metabolic disorders, such as Marfan syndrome, Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome, Sotos syndrome and Homocystinuria. Children may require growth reductive treatment if the predicted adult height would be excessive and unacceptable. Some hormonal, high doses of sex steroids, or surgical, bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula, treatment is currently available to reduce adult height.
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PMID:Tall stature in children and adolescents. 3274 12


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