An apparently new autosomal recessive syndrome with facial dysmorphism, macrocephaly, myopia and Dandy-Walker malformation

In this report we describe an apparently new MCA-MR syndrome with Dandy-Walker malformation in three severely mentally retarded siblings born to normal, non-consanguineous parents. In addition, they presented macrocephaly, facial dysmorphism, extreme myopia and brachytelephalangy with short and broad finger-nails.     

Cleft palate-lateral synechiae syndrome: Report on three new patients with additional findings and evidence for variability and heterogeneity

We report on 3 Brazilian children with short stature, microcephaly, cleft palate, lateral synechiae, and mild mental retardation. One patient was an isolated case and the other had an equally affected brother. Genetic aspects and phenotypic manifestations are compared with those of previous reports with oral synechiae. Recurrence in sibs suggests autosomal recessive inheritance. © 1993 Wiley-Liss, Inc.     

Deafness,onycho-osteodystrophy,mental retardation (DOOR) syndrome

We report two patients with sensorineural deafness, onycho- and osteodystrophy of fingers and toes, and mental retardation (DOOR syndrome). In addition, one patient, the only son of consanguineous parents, had seizures and hypoplasia of the optic nerves. The second patient, a male, was the only one affected in a sibship of three.     

New autosomal recessive syndrome of mental retardation,epilepsy, short stature,and skeletal dysplasia

We describe 4 sibs, 2 males and 2 females, affected with a new autosomal recessive MCA/MR syndrome of short stature, cerebral atrophy, epilepsy, skeletal abnormalities, and moderate to severe mental retardation. © Wiley-Liss, Inc.     

Onychotrichodysplasia and chronic neutropenia without mental retardation (ONS): a second case report

Onychotrichodysplasia, chronic neutropenia and mental retardation syndrome (ONMRS) is a rare autosomal recessive mutation, mostly reported in patients of Mexican ancestry. We describe a second patient with onychotrichodysplasia and chronic neutropenia without mental retardation (ONS). It is unclear if ONS found in the two European patients with normal mental development is due to genetic heterogeneity or variable expressivity of the same syndrome.     

Congenital ichthyosis with alopecia, eclabion, ectropion and mental retardation - a new genetic syndrome

A syndrome with severe generalized congenital ichthyosis, alopecia, eclabion, ectropion and mental retardation without neurological symptoms or macular changes in the eyes was seen in two sibs and in two aunts and uncles in an inbred North-Swedish family. The clinical picture of the patients in the present family strongly deviated from that seen in the Sjögren-Larsson syndrome found in the same area. This could be a new syndrome with autosomal recessive inheritance.     

Bilateral ulna hypoplasia,club feet,and mental retardation: A new mesomelic syndrome

We report on 2 sibs with a previously unreported type of mesomelia of the upper limbs due to ulnar hypoplasia. Prenatal diagnosis was made by ultrasound during one pregnancy and an affected fetus was confirmed. This family documents a previously unreported autosomal recessive syndrome. © 1995 Wiley-Liss, Inc.     

A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3

Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.     

A form of X-linked mental retardation with marfanoid habitus

A kindred has been studied in which mental retardation and marfanoid clinical features are present in several individuals. The pedigree is consistent with X-linked recessive inheritance. Four affected males aged 12-18 years and four obligate carriers have been identified. Clinical findings in the 4 affected males included a tall slender habitus (3) (the fourth was tall but muscular), a long-narrow face (3), large head (4), highly arched palate (4), small mandible (4), abnormal speech (4), hypernasal voice (3), joint hyperextensibility (3), borderline to large testes (3), pectus excavatum (2), atrial septal defect (1), and a double row of teeth (1). Mental retardation (4) ranged from mild to severe; abnormal behavior included hyperactive and aggressive behavior (2), autistic-like (1) and jovial behavior (1). One and possibly two, males had absence of the corpus callosum. Chromosome studies on all were normal; no marker X was observed. We believe this family probably represents a new form of X-linked mental retardation.     

Syndrome of short stature,microcephaly, mental retardation,and multiple epiphyseal dysplasia—Lowry-Wood syndrome

We describe a brother and a sister with a syndrome of short stature, microcephaly, mental retardation, and multiple epiphyseal dysplasia. The parents were normal. This appears to be the second example of the syndrome first described by Lowry and Wood [1975] in two boys who had epiphyseal dysplasia, short stature, microcephaly, and nystagmus; one of these patients was mildly mentally retarded. The Lowry-Wood syndrome probably is an autosomal recessive trait.     

X-linked dysmorphic syndrome with mental retardation

We present a dysmorphic syndrome in eight males of the same family (four brothers, three cousins and one uncle) that is characterised by: mental retardation, facial dysmorphia, abnormal growth of teeth, skin dimple at the lower back, clinodactyly, patella luxation, malformation of lower limbs, abnormalities of the fundus of the eye and subcortical cerebral atrophy. These physical defects do not correspond to any previously described syndrome, which suggests that it is a new syndrome. According to the model of heredity this syndrome could be due to a mutant gene situated in the X-chromosome.     

Homozygosity mapping in outbred families with mental retardation

Autosomal recessive mental retardation (AR-MR) may account for up to 25% of genetic mental retardation (MR). So far, mapping of AR-MR genes in consanguineous families has resulted in six nonsyndromic genes, whereas more than 2000 genes might contribute to AR-MR. We propose to use outbred families with multiple affected siblings for AR-MR gene identification. Homozygosity mapping in ten outbred families with affected brother-sister pairs using a 250 K single nucleotide polymorphism array revealed on average 57 homozygous regions over 1 Mb in size per affected individual (range 20-74). Of these, 21 homozygous regions were shared between siblings on average (range 8-36). None of the shared regions of homozygosity (SROHs) overlapped with the nonsyndromic genes. A total of 13 SROHs had an overlap with previously reported loci for AR-MR, namely with MRT8, MRT9, MRT10 and MRT11. Among these was the longest observed SROH of 11.0 Mb in family ARMR1 on chromosome 19q13, which had 2.9 Mb (98 genes) in common with the 5.4 Mb MRT11 locus (195 genes). These data support that homozygosity mapping in outbred families may contribute to identification of novel AR-MR genes.     

一个遗传性智力迟缓家系的分析

目的 寻找由DNA损伤引起的人类表型缺陷，为人类遗传资源的收集与保藏以及人类基因结构与功能的研究打下基础。方法 通过实地调查得到表型缺陷家系，然后进行系谱分析。结果 得到一个遗传性智力迟缓家系，3代11位成员中有2例患者。结论 遗传性智力迟缓是由DNA损伤引起的人类表型缺陷；该病症符合X-连锁隐性遗传。     

An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4

We report on three siblings with a novel mental retardation (MR) syndrome who were born to distantly related Iranian parents. The clinical problems comprised severe MR, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bilateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4 flanked by SNPs rs728293 (4p12) and rs1105434 (4q12). This interval contains more than 40 genes, none of which has been implicated in MR so far. The identification of the causative gene defect for this syndrome will provide new insights into the development of the brain and the eye.     

Short stature,brachydactyly, nail dysplasia,and mental retardation: Further observation of the Tonoki syndrome

We studied a patient with microcephaly, short stature, type B brachydactyly, nail dysplasia, skeletal anomalies, and mental retardation. The mother of the propositus has brachydactyly of thumbs and a similar physiognomy without mental retardation. This appears to be another observation of the Tonoki syndrome, a distinct autosomal dominant or X-linked clinical entity. Am. J. Med. Genet. 80:403–405, 1998. © 1998 Wiley-Liss, Inc.     

A novel nonsense mutation in TUSC3 is responsible for non-syndromic autosomal recessive mental retardation in a consanguineous Iranian family

The genetic basis of autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to suspect that the number of underlying gene defects may well go beyond 1,000. To date, however, only less than 10 genes have been implicated in non‐specific/non‐syndromic ARMR (NS‐ARMR). As part of an ongoing systematic study aiming to identify further ARMR genes, we investigated a consanguineous family with three patients with NS‐ARMR. By linkage analysis and subsequent mutation screening we identified a novel nonsense mutation (c.163C > T [p.Q55X]) in the second exon of the TUSC3 gene. This is the third MR causing defect in TUSC3 to be described and the second independent mutation in this gene in a cohort of more than 200 ARMR families from the Iranian population. This argues for a more prominent role of TUSC3 in the etiology of this genetically heterogeneous disorder as compared to most of the other so far identified ARMR genes. © 2011 Wiley‐Liss, Inc.     

Coffin-Lowry syndrome in sibs

The authors report the Coffin-Lowry syndrome in two sibs and suggest autosomal recessive inheritance of the condition in this family.     

Microcephaly,microphthalmia, congenital cataract,optic atrophy,short stature,hypotonia, severe psychomotor retardation,and cerebral malformations: a second family with micro syndrome or a new syndrome?

We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed.     

Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of a new case

A syndrome of ocular and cutaneous hypopigmentation, severe mental retardation with spastic tetraplegia and athetosis was first observed by Cross in three siblings of an inbred Amish family. Since then, seven other patients, three sporadic and four with familial recurrence, have been reported in the literature, confirming the autosomal recessive inheritance. The clinical spectrum of the syndrome has been expanded to include true developmental defects of the CNS such as cystic malformation of the posterior fossa of the Dandy-Walker type. We report a new case of Cross syndrome.