Additional case of Neuh?user megalocornea and mental retardation syndrome with congenital hypotonia.

We report on a 3-1/2-year-old Spanish girl with the Neuh?user megalocornea and mental retardation syndrome. A review shows that megalocornea, mental retardation, and, presumably, hypotonia, are the major manifestations for diagnosis. The facial appearance of the typical cases is characterised by frontal bossing, broad nasal bridge, mild hypertelorism, long upper lip, and small mandible.     

Megalocornea, macrocephaly, mental and motor retardation (MMMM)

Two patients with macrocephaly, mild mental retardation and megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome.     

Megalocornea-mental retardation syndrome: An additional case

Oral-facial-digital syndromes (OFDS) constitute a heterogeneous group of entities whose clinical manifestations are often overlapping. We report on a 23-week-old aborted fetus who showed a transitional phenotype between OFD II and OFD VI syndromes. © 1994 Wiley-Liss, Inc.     

Distinct facial appearance with nasal hypoplasia, constipation, severe mental retardation and hypotonia in two unrelated young males

In this report we describe two unrelated young males with severe mental retardation, persisting hypotonia, and constipation. A maternal uncle of one of these two boys died at the age of 18 months and presented the same clinical symptoms. The triad mental retardation, hypotonia, constipation is a characteristic finding in the FG syndrome, an X-linked mental retardation syndrome. At the present time, there is increasing evidence that the FG syndrome-phenotype may be present in different XLMR conditions, e.g. the fragile X syndrome. In addition to the triad severe mental retardation, hypotonia, constipation, the present two male index patients had a characteristic facial appearance with nasal hypoplasia, relative microcephaly and pre-and postnatal overgrowth. The question is raised whether the present two males are examples of a specific entity within the FG-syndrome-like phenotype.     

X-linked mental retardation with neonatal hypotonia in a French family (MRX15): Gene assignment to Xp11.22-Xp21.1

Linkage analysis was performed in a family with non-specific X-linked mental retardation (MRX 15). Hypotonia in infancy was the most remarkable physical manifestation. The severity of mental deficiency was variable among the patients, but all of them had poor or absent speech. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS1126, DXS255, and DXS573 (Zmax = 2.01) and recombination was observed with the two flanking loci DXS164 (Xp21.1) and DXS988 (Xp11.22), identifying a 17 cM interval. This result suggests a new gene localization in the proximal Xp region. In numerous families with non-specific X-linked mental retardation (MRX), the corresponding gene has been localized to the paracentromeric region in which a low recombination rate impairs the precision of mapping. © 1996 Wiley-Liss, Inc.     

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.     

Unilateral radio-ulnar synostosis,generalized hypotonia,developmental retardation,and a characteristic facial appearance in sibs: A new syndrome

We report on 2 sibs with generalized hypotonia, developmental retardation, unilateral radio-ulnar synostosis, and a characteristic facial appearance. We propose that they have a new autosomal recessive syndrome. © 1992 Wiley-Liss, Inc.     

A microdeletion syndrome due to a 3-Mb deletion on 19q13.2 – Diamond–Blackfan anemia associated with macrocephaly, hypotonia, and psychomotor retardation

We report on a boy with congenital pure red blood cell aplasia [Diamond Blackfan anemia (DBA)] and severe congenital hypotonia, macrocephaly, hypertelorism, a broad and tall forehead, medial epicanthus, and facial hypotonia with mouth-breathing and drooling, an affable and out-going personality, and a general psychomotor retardation. These features show similarity to the phenotype of the X-linked FG syndrome. DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. He had a normal 46, XY karyotype, but fluorescence in situ hybridization (FISH) analysis to metaphase chromosomes revealed a 3-Mb deletion on 19q13.2. This chromosomal region has previously been linked to the DBA phenotype and one 19q13 microdeletion has been identified in a patient with DBA. This deletion coincides with the deletion reported here. We suggest that the complex phenotype of our patient, including both DBA and the associated features, represent a microdeletion syndrome.     

Alopecia/mental retardation syndrome

We report on an African-American patient with alopecia universalis, microcephaly, hypogonadism, and mental and growth retardation, and compare his phenotype to others with recessive alopecia/mental retardation syndromes in the literature. Our patient represents the first case reported from nonconsanguineous African-American parents. © 1995 Wiley-Liss, Inc.     

Two siblings with mental retardation and progressive spasticity

Nicolaides P, Baraitser M, Brett EM. Two siblings with mental retardation and progressive spasticity.
Clin Genet 1993: 43: 312–314. © Munksgaard, 1993
We describe two siblings with a progressive form of spastic paraplegia, seizures and non-progressive mental retardation.     

Familial mental retardation

Familial patterns of mental retardation were examined among white and black children in the NINCDS Collaborative Perinatal Project population. Among whites, the mildly retarded children had more affected relatives than did the severely retarded, consistent with the traditional two-group theory of mental retardation. In blacks, where differences in family patterns between the mildly and the severely retarded were less clear, most retardation appeared to be of the cultural-familial type.     

A novel nonsense mutation in CUL4B gene in three brothers with X‐linked mental retardation syndrome

Badura‐Stronka M, Jamsheer A, Materna‐Kiryluk A, Sowińska A, Kiryluk K, Budny B, Latos‐Bieleńska A. A novel nonsense mutation in CUL4B gene in three brothers with X‐linked mental retardation syndrome. Cabezas syndrome (MIM 300354) is a recently identified syndromic form of X‐linked mental retardation (XLMR) caused by mutations in the CUL4B gene. In total, nine XLMR families carrying mutations in the CUL4B gene have been described to date. Here, we present a detailed clinical phenotype of three affected brothers of Polish descent. Based on the symptoms, we made a clinical diagnosis of Cabezas syndrome, which was subsequently confirmed by identification of a novel nonsense mutation (c.2107A→T, p.703K→X) in exon 18 of the CUL4B gene. The mutation was inherited from an asymptomatic mother and was present in all three affected brothers. The patients presented with typical features of Cabezas syndrome, such as severe mental retardation, speech impairment, hyperactivity, seizures, intention tremor, inguinal hernia, small feet, and craniofacial dysmorphism. In addition to previously described symptoms, syndactyly of the second and third toes and skin manifestations (hyperhydrosis and keratosis pilaris) were present in our cases. Our report provides further support that Cabezas syndrome is a recognizable syndromic form of XLMR. We conclude that the CUL4B gene should be screened in males with severe speech impairment and primary intention tremor, especially if characteristic facial dysmorphism is also present.     

A new X-linked multiple congenital anomalies/ mental retardation syndrome

We report on 2 boys, the sons of sisters, and their mother's brother who have a new, X-linked multiple congenital anomalies/mental retardation (MCA/MR) syndrome. The propositus was a 16-month-old caucasian male with 1)mental retardation, 2) congenital microcephaly, 3)postnatal growth deficiency, 4)ridged metopic suture with narrow bifrontal diameter, 5)upslanted palpebral fissures with persistent epicanthal folds, strabismus, and lacrimal duct obstruction, 6)narrow palate, 7)macrodontia, 8)anteverted ears, 9)atrial septal defect, 10)dry brittle scalp hair and 11)cutis marmorata. His chromosomes were normal. His cousin and uncle were similarly affected. This distinctive MCA/MR syndrome is added to the list of X-linked malformation syndromes known at the present time.     

New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement—the CFC syndrome

Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio-Facio-Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.     

Cardio-facio-cutaneous (CFC) syndrome: Report of an adult without mental retardation

We report on a 25-year-old woman with typical manifestations of the cardio-facio-cutaneous (CFC) syndrome, but without mental retardation. She had valvular and infundibular pulmonic stenosis, brittle and woolly hair with patchy alopecia, scant body hair, dry and hypohydrotic skin, and characteristic facial traits. To our knowledge, this is the first case of CFC syndrome without mental retardation but typical cutaneous findings. © 1996 Wiley-Liss, Inc.     

Male pseudohermaphroditism in sibs with the α-thalassemia/mental retardation (ATR-X) syndrome

Genital abnormalities have been noted in several patients with the X-linked form of α-thalassemia and mental retardation syndrome (ATR-X). The initial clinical report of the condition documented a phenotypic female with 46,XY karyotype. To this we now add 2 further siblings with abnormalities of the external genitalia, manifesting as male pseudohermaphroditism. © 1995 Wiley-Liss, Inc.     

Chorio-retinal dysplasia, microcephaly and mental retardation. An autosomal dominant syndrome

A condition is described which is characterized by chorio-retinal dysplasia, microcephaly and mental retardation, transmitted in an autosomal dominant fashion with variable expressivity. It is suggested that this condition is a distinct autosomal dominant syndrome.     

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.     

PAX6 mutation in a family with aniridia, congenital ptosis, and mental retardation

Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded by polymorphism studies and fluorescence in situ hybridization analysis. Mutation screening of the PAX6 gene revealed the presence of a transversion C719A, resulting in the substitution of arginine for serine at residue 119. We suggest that this missense mutation is responsible both for aniridia and ptosis, and possibly also for the observed cognitive dysfunction in this family.