Genetics,mental retardation,and the forging of new alliances

The lives of people with intellectual disabilities are tightly intermeshed with the philosophies and practices of special educators, therapists, psychologists, social workers, and others who make up the mental retardation field. These nonmedical workers represent a kind of extended family, which can strongly influence the decisions made and services received by the people they serve. By contrast, most individuals with mental retardation do not have extraordinary medical needs, and healthcare professionals play only a minor role in their human services family. There are deeply rooted historical differences between the medical model of mental retardation with which genetics professionals are familiar and the philosophies embraced by nonmedical workers who dominate the mental retardation field. These contrasts have an important impact on the genetic diagnostic process, as well as a more global effect on mental retardation research. Without the full participation of teachers, therapists, psychologists, and others outside the medical setting, many practical applications of genetic research can neither be implemented nor expanded upon, and an important opportunity for cross-fertilization is lost. It is in the interest of the genetics community to take advantage of recent overtures by the mental retardation field to forge new alliances and broaden its perspectives on intellectual disability.     

New X-linked syndrome with severe mental retardation,severely impaired vision,severe hearing defect,epileptic seizures,spasticity, restricted joint mobility,and early death

A family with an X-linked mental retardation syndrome involving seven children in two generations is reported. The syndrome includes microcephaly, severe mental retardation, optic atrophy with severely impaired vision or blindness, a severe hearing defect, spasticity, epileptic seizures, restricted movement of the large joints, and death in infancy or early childhood. We conclude that this is a distinct, previously unrecognized X-linked mental retardation syndrome. © 1993 Wiley-Liss, Inc.     

A new syndrome of dwarfism, brachydactyly, nail dysplasia, and mental retardation in sibs

We describe a new multiple congenital anomaly/mental retardation (MCA/MR) syndrome in chromosomally normal sibs. Both had microcephaly, a "coarse" face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a "coarse" face, digital anomalies, dwarfism, and severe mental retardation. The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X-linked semidominant gene.     

X-linked mental retardation, growth retardation, deafness and micro-genitalism. A second familial report

The association of X-linked mental retardation with growth retardation, deafness and microgenitalism in a second family confirms the existence of a new syndrome.     

Apparently new MCA/MR syndrome in sibs with cleft lip and palate and other facial,eye, heart,and intestinal anomalies

We report on a sister and brother with severe mental retardation, bulbous tip of the nose, long columella, cleft lip and palate, heart and intestinal anomalies, and growth retardation. This appears to be a previously unreported, autosomal recessive condition, given high resolution prometaphase chromosomes are normal.     

Three sibs with phalangeal anomalies, microcephaly, severe mental retardation, and neurological abnormalities.

This paper describes three children of a Pakistani first cousin marriage with a distinctive, non-progressive disorder characterised by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, a characteristic face, and severe mental retardation. This combination of features seems to be distinct and to represent a new autosomal recessive syndrome.     

Psychomotor retardation and agitation in depression. Relationship to age, sex, and response to treatment

Patients with primary affective disorder who had either psychomotor agitation alone or psychomotor retardation alone were studied. Compared to psychomotor retardation, psychomotor agitation appears to be seen more frequently in women, older patients, and individuals who have a late onset to their illness. In addition, those with agitation alone appeared to have a better and faster response to electroconvulsive therapy.     

Mental retardation,short stature,minor skeletal anomalies,craniofacial dysmorphism and macrodontia in two sisters and their mother

Mental retardation associated with short stature, craniofacial dysmorphism, macrodontia and minor skeletal anomalies is reported in two sisters and their mother.
The similarity with and the relationship to the KBG syndrome is discussed and the importance of clinical syndrome identification in familial mental retardation is emphasised.     

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.     

Immunity and depression: Insomnia,Retardation, and reduction of natural killer cell activity

Depressed patients show a reduction of natural killer (NK) cell activity which may be associated with specific depressive symptoms. The present study demonstrated that sleep disturbance and retardation, but not other depressive symptoms, were negatively correlated with NK activity in 38 depressed patients. Specific behavioral changes in depression such as sleep disturbance and retardation were found to predict 16% of the variance of cytotoxicity levels in depression.     

Blepharophimosis, eczema, and growth and developmental delay in a young adult: late features of Dubowitz syndrome?

The Dubowitz syndrome is a rare autosomal recessive multiple congenital anomaly/mental retardation syndrome. We report here a case of a young adult presenting with several features consistent with this diagnosis. The differential diagnosis is discussed with respect to the absence of microcephaly and intrauterine growth retardation.     

Young-Simpson syndrome: further delineation of a distinct syndrome with congenital hypothyroidism, congenital heart defects, facial dysmorphism, and mental retardation

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.     

A de novo 12q13.11 microdeletion in a patient with severe mental retardation, cleft palate, and high myopia

We report a de novo 12q13.11 deletion of 1.3?Mb in an 10-year-old dysmorphic girl with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome consisting mainly of severe mental retardation, cleft palate, and high myopia. The deleted region encompasses 16 RefSeq genes. Among these, it is hypothesized that haploinsufficiency of AMIGO2 is potentially responsible for the mental retardation of this patient, and of COL2A1 for the cleft palate and high myopia.     

Cataract, hypertrichosis, and mental retardation (CAHMR): a new autosomal recessive syndrome.

We have studied 2 Egyptian sibs (the offspring of normal first cousins) with congenital cataract, hypertrichosis, mental retardation, and normal chromosomes. Review showed that the condition of our patients was not similar to any previously reported entity. POSSUM lists 84 syndromes with any of the above 3 main traits. Two disorders with cataract and mental retardation, Martsolf syndrome and Mollica-Pavone-Anterer syndrome, have overlapping manifestations and therefore are particularly differentiated from our cases. We suggest that the association of congenital cataract, hypertrichosis, and mental retardation observed in this report represents a new autosomal recessive syndrome.     

Callosal defect, microcephaly, severe mental retardation, and other anomalies in three sibs

This study concerns an apparently lethal and previously undescribed syndrome of hypoplastic corpus callosum, microcephaly, severe mental retardation, preauricular skin tag, camptodactyly, growth retardation, and recurrent bronchopneumonia. This combination of anomalies is probably inherited as an autosomal recessive trait. A brief literature review of the anomalies or syndromes associated with callosal defects is discussed.     

Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.     

A syndrome with multiple malformations, mental retardation, and ACTH deficiency

We report on a patient with severe pre- and post-natal growth retardation, moderate mental retardation, microcephaly, unusual face with marked micrognathia and cleft palate, minor skeletal abnormalities, atrioseptal defect, hypospadias, hearing loss, and secondary adrenal insufficiency due to isolated ACTH deficiency diagnosed at 7 years of age. Family history was negative. Adrenal insufficiency is an uncommon feature in multiple malformation syndromes and may thus serve as a diagnostic handle for recognizing other possible patients with a similar syndrome.     

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.     

Growth retardation, alopecia, pseudo-anodontia, and optic atrophy--the GAPO syndrome: report of a patient and review of the literature

The GAPO syndrome is a rare but distinct autosomal-recessive disorder. The term GAPO is an acronym for the manifestations of Growth retardation. Alopecia, Pseudo- anodontia (failure of tooth eruption), and progressive Optic atrophy. We are aware of five other published patients. All have a strikingly similar appearance. This, along with other distinct manifestations, should allow clear differentiation from other causes of growth retardation. The hypothesis of autosomal-recessive inheritance is based on parental consanguinity and affected sibs in several cases.     

New X-linked mental retardation disorder with Dandy-Walker malformation, basal ganglia disease, and seizures

We report on a 4 generation family of individuals with an X-linked form of mental retardation involving 9 affected males and 5 obligate carrier females. Key manifestations include severe mental retardation, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, presence of a long, narrow face with coarse features, cystic enlargement of the fourth ventricle with cerebellar hypoplasia (Dandy-Walker malformation), and iron accumulation in the basal ganglia with neuroaxonal dystrophy similar to Hallervorden-Spatz disease. Of the 5 known heterozygotes, 3 are dull intellectually, and one of the 3 developed a "presenile dementia." At autopsy she had iron deposition and neuroaxonal dystrophy in the basal ganglia and atrophy of the cerebral cortex. Although the clinical findings among relatives are variable, we conclude that this is a distinct, previously unrecognized X-linked mental retardation syndrome.