Radio-ulnar synostosis,short stature,microcephaly, scoliosis,and mental retardation

We report on a 9-year-old boy with radioulnar synostosis, short stature, microcephaly, soliosis, and mental retardation. We propose that he has a new syndrome. © 1995 Wiley-Liss, Inc.     

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.     

Acquired alopecia, mental retardation, short stature, microcephaly, and optic atrophy.

We report on a female patient who had acquired total alopecia, short stature, microcephaly, optic atrophy, severe myopia, and mental retardation. A survey of published reports failed to show an identical patient, despite various similar cases.     

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.     

A syndrome of microcephaly, eye anomalies, short stature, and mental deficiency

We have studied a mother and son with a previously apparently undescribed syndrome of microcephaly, eye defects, small ears, mild mental deficiency, and short stature. The syndrome appears to be an autosomal or X-linked dominant trait. The cat eye syndrome, blepharophimosis or Kohn-Romano syndrome, Rieger syndrome, and other disorders are discussed in relationship to this entity.     

X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family

X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism. Two-point linkage analysis with 24 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 6 cM interval in Xp22.1-p21.3, with a maximum LOD score of 2.61 for markers DXS989 and DXS1061 at theta = 0.00. No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1. These data indicate that the interval Xp22.1-p21.3 contains at least one additional MRXS gene.     

A new syndrome with mental retardation, short stature and an Xq duplication

We describe a new X-linked syndrome of marked short stature, severe intellectual handicap and an unusual facial appearance. High resolution prometaphase banding showed affected males to have an X chromosome tandem duplication; their karyotypes were designated 46,dup(X) (q13.1-q21.1)Y. In carrier females the abnormal X chromosome was late replicating. To verify the duplication, gene dosage studies were performed using an enzyme assay and DNA techniques. Prenatal diagnosis is available for carrier females using chromosome analysis of amniocytes or chorionic villi.     

New X-linked syndrome of mental retardation, short stature, and hypertelorism

We present a three-generation family with five retarded, abnormally appearing males and two abnormally appearing females (presumably manifesting carriers). The phenotype of the patients is different from that of all other previously described types of X-linked mental retardation (XLMR). The patients had prominent forehead, frontal bossing, hypertelorism, broad nasal tip, and anteverted nares. Chromosomes were normal including fragile X analysis. Skeletal roentgenograms were normal.     

Postnatal short stature,microcephaly, severe syndactyly of hands and feet,dysmorphic face,and mental retardation: a new syndrome?

We report on a 2 year old boy with an apparently previously undescribed multiple congenital anomaly/mental retardation syndrome characterised by postnatal short stature, postnatal microcephaly, dysmorphic face, syndactyly 2/5 of the hands and 1/4 of the feet, and brachymesophalangy of fingers 2 and 5.     

Syndrome of short stature, mental deficiency, microcephaly, ectodermal dysplasia, and multiple skeletal anomalies

We report on two brothers with mental deficiency, short stature of prenatal onset, microcephaly, alopecia/sparse hair, follicular ichthyosis, multiple skeletal anomalies, and recurrent respiratory infections. The younger brother has celiac disease, cryptorchidism, inguinal herniae, and hypohidrosis, while the older brother has hidrotic ectodermal dysplasia, juvenile autoimmune thyroiditis, hypolacrimation, photophobia, and optic atrophy. Striking resemblance exists between our patients and those previously reported by Schinzel ?1980: Helv Paediatr Acta 35:243-251 and van Gelderen ?1982: Am J Med Genet 13:383-387. The fact that boys are born to young and healthy nonconsanguineous parents and there are no other affected relatives suggests autosomal or X-linked recessive inheritance or parental germinal mosaicism for a dominant mutation.     

GMS syndrome: A new dominant condition with goniodysgenesis,mental retardation,and short stature

We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance.     

A syndrome of primary gonadal failure, short stature, mitral valve prolapse, and mental retardation

Two brothers referred for hypogonadism presented with short stature, mild mental retardation, and minor anomalies. In addition, both patients had hypogonadism due to primary gonadal failure and mitral valve prolapse, in the absence of other heart defects. A complete hormonal evaluation in one of the patients showed abnormal growth hormone (GH) and gonadotropin responses to different stimuli, findings suggestive of a disorder of hypothalamic-pituitary regulation. Both patients had normal chromosomes (46,XY) as did their mother (46,XX), who had some of the clinical manifestations found in her sons but in a milder form. We propose that this is a new syndrome.     

Tall stature,microcephaly, hypotonia,advanced bone age,and unusual infra-auricular creases

The patient is a 16-month-old girl with tall stature, hypotonia, unusual facial appearance, acquired microcephaly, advanced bone age without apparent sexual precocity or acromegaly, and symmetric horizontal creases below the earlobes. Her combination of anomalies appears to constitute a previously unreported syndrome. Am. J. Med. Genet. 75:261–262, 1998. © 1998 Wiley-Liss, Inc.     

Mental retardation,distinct facial changes,short stature,obesity, and hypogonadism: A new X-linked mental retardation syndrome

We describe a 3-year-old boy and his 2 maternal uncles with moderate to severe mental retardation, short stature, mild obesity, hypogonadism, a low total finger ridge count, and a distinctive face characterized by bitemporal narrowness, almond-shaped palperbral fissures, depressed nasal bridge, anteverted nares, short and inverted-V-shaped upper lip, and macrostomia. Two other males in this family who had similar facial anomalies and developmental delay died in early infancy and midchildhood. This apparently new disorder is reminiscent of, but distinct from, the Prader-Willi syndrome, and is likely inherited as an X-linked recessive trait. Preliminary studies with DNA probes are consistent with an X-linked locus and permit exclusion of distal Xp and Xq regions as the site of this mutation.     

Multicore disease in sibs with severe mental retardation, short stature, facial anomalies, hypoplasia of the pituitary fossa, and hypogonadotrophic hypogonadism

We describe a family in which two adult sibs presented with a history of congenital nonprogressive myopathy, severe mental retardation and evidence of mild generalized weakness, short stature, musculoskeletal deformities, facial anomalies, sexual infantilism, and radiologic evidence of pituitary hypoplasia. The parents were first cousins. An excess of other, apparently unrelated, genetic conditions were present in other family members. Results of histochemical and electron microscopy studies of muscle biopsies from both affected individuals were compatible with multicore disease. This newly described syndrome likely is an autosomal recessive trait and appears to be the first reported association of multicore disease with mental retardation.     

A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25-q26

X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.     

Severe mental retardation, cataracts, short stature, and primary hypogonadism in two brothers

Two severely mentally retarded brothers are described who had a similar facial appearance, cataracts, short stature, minor digital abnormalities, and primary hypogonadism. Their parents were first cousins. Numerous laboratory investigations failed to elucidate a basic metabolic cause for their disorder.     

Mapping of a gene (MRXS9) for X-linked mental retardation, microcephaly, and variably short stature to Xq12-q21.31.

Three boys from two families were identified as having a syndrome of X-linked mental retardation (XLMR) with microcephaly and short stature, clinically resembling Renpenning syndrome but with normal size of testicles in affected men. When the effort to map the gene for the above condition was initiated, it was realized that the two families were actually related to each other. Over 50 polymorphic markers of known locations along the X chromosome were scored in this family in a study to map the disease gene. Nine affected and four unaffected males were genotyped to produce a maximum LOD score of 4.42 at zero recombination with markers in proximal Xq. The results indicate that the gene responsible for this disorder is located in the cytogenetic Xq12 to Xq21.31 interval of the X chromosome within a section of chromosome of about 17 cM between the AR and DXS1217 loci over some 25 mb. Since the gene for the X-linked mental retardation from the original Saskatchewan family described by Renpenning [Renpenning et al., 1962: Can Med Assoc J 87:954-956; Fox and Gerrard, 1980: Am J Med Genet 7:491-495] was recently mapped to a different nonoverlapping region [Stevenson et al., 1998: Am J Hum Genet 62:1092-1101] this would appear to be a separate disorder.     

A de novo complex chromosomal rearrangement with nine breakpoints characterised by FISH in a boy with mild mental retardation, developmental delay, short stature and microcephaly

A de novo complex chromosome rearrangement (CCR) involving chromosomes 1, 6, 7, 15 and Y was detected in a boy with mental retardation, short stature, and microcephaly. Fluorescence in situ hybridisation (FISH) with whole chromosome painting libraries, band-specific cosmids and telomeric probes was essential for the characterisation of the rearrangement. The CCR was shown to be the result of at least nine chromosomal breaks and involved the alternating insertion of two segments of the short arm of chromosome 1 and two segments of the long arm of chromosome 6 into a novel derived chromosome 7. A non-reciprocal translocation between the distal short arm of the same chromosome 7 and the distal long arm of the Y chromosome was also found, together with a paracentric inversion of the long arm of chromosome 15. The only detectable imbalance was a deletion of the heterochromatic Yq telomeric region. FISH investigations in this case have revealed an additional complexity in this CCR, which has implications for reproductive risk assessment and genetic counselling.