Aarskog-Scott syndrome: clinical and molecular characterisation of a family with the coexistence of a novel FGD1 mutation and 16p13.11-p12.3 microduplication.

Aarskog-Scott syndrome (AAS), also known as facio-genital dysplasia or faciodigitogenital syndrome, is a rare genetic disorder clinically characterised by facial, limb and genitalanomalies. Although also autosomal dominance and recessive patterns have been reported, up to now, only an X linked form associated to mutations of the FGD1 gene has been recognised as causative for this syndrome.In this case report, we describe a large Italian family in which three members across three generations show classical features of the syndrome. The youngest patient, the proband, and his mother were both molecularly studied and characterised for the not previously reported variant c.1828C>T (p. Arg610*) in the FGD1 gene but with the classic phenotype of AAS. Additionally, both the proband and his mother present a 2.5 Mb 16p13.11-p12.3 microduplication, a genetic variant still unclear for the phenotypic consequences: the co-occurrence of the two rare conditions is discussed for the possible clinical significance.

[Living with achondroplasia- how do young persons with disproportional short stature rate their quality of life and which factors are associated with quality of life?]. / Leben mit Achondroplasie.

OBJECTIVE: Presently, little is known aqout the quality of life (QoL) as well as the strengths and difficulties of young people with achondroplasia. This study describes these patient-reported indicators and identifies possible correlates. METHOD: At the invitation of a patient organization, a total of 89 short-statured patients aged 8 to 28 years and their parents participated in this study. QoL was assessed cross-sectionally with both generic and disease-specific instruments and the Strengths and Difficulties Questionnaire (SDQ) as a brief behavioral screening. In addition to descriptive analyses, patient data were compared with a reference population. Hierarchical regression analyses reflecting sociodemographic, clinical, and psychological variables were conducted to identify correlates of QoL. RESULTS: QoL and the strengths and difficulties of young patients with achondroplasia did not differ substantially from a healthy norm sample. However, the participants reported more behavioral problems and limitations in their physical and social QoL compared to patients with another short stature diagnosis. Strengths and difficulties, height-related beliefs, and social support correlated significantly with QoL. Adding psychological variables to the regression model increased the proportion of variance explained in QoL. CONCLUSIONS: Young persons with achondroplasia did not differ in their QoL and strengths and difficulties from healthy controls. Characteristics such as height appear less important for the self-perceived QoL than are strengths and difficulties and protective psychosocia~factors.

Health-related quality of life and socioeconomic situation among diastrophic dysplasia patients in Finland.

OBJECTIVE: The purpose of the present study was to gain a comprehensive view of the quality of life and socio-economic conditions in a more representative sample of patients with diastrophic dysplasia than previously presented. METHODS: The study sample comprised 115 patients with diastrophic dysplasia, aged over 18 years. The patients were contacted, and 68 patients (59%) agreed to participate in the study. They answered a structured questionnaire, which included the items of RAND-36 and Finn-Health Assessment Questionnaire (Finn-HAQ) questionnaires. The Finn-HAQ items were linked to the categories of the International Classification of Functioning, Disability and Health (ICF). Population controls for matching the participating patients for age and sex were identified in the Finnish population registry. Demographic and social factors (educational status, employment status and household income) were collected in separated questions. RESULTS: RAND-36 showed significantly lower physical functioning in the group of diastrophic dysplasia patients than in the control group. Also, the differences in scores for energy and social functioning were significant. In the mental component scales, no significant difference was found between the groups. When compared with the controls, we found significantly lower levels in all 3 ICF components of functioning in the group of patients when Finn-MDHAQ items linked to ICF were used. Almost 75% of patients with diastrophic dysplasia belonged to the group of people with minor/low income. Some or clear worsening of economic situation due to diastrophic dysplasia was reported by 25 (58%) female and 17 (68%) male patients. CONCLUSION: In their daily living, patients with diastrophic dysplasia have marked physical difficulties, which affect their quality of life, participation in society and their financial situation. It seems that the mental situation is not greatly affected, but a more detailed study is needed to evaluate and illuminate the psychological consequences of this severe skeletal dysplasia. Overall, the pieces of information in the present study are of high importance when designing and reorganizing rehabilitation and in supportive therapy and treatment of patients with diastrophic dysplasia.

Longe da árvore: pais, filhos e a busca da identidade

Diagnosticado com dislexia na infância, Andrew Solomon conta que a superação dessa deficiência só foi possível porque ele pôde contar com a paciente dedicação dos pais, em especial de sua mãe, num lar estruturado. Criado num ambiente privilegiado - a culta classe média judaica de Nova York -, Solomon sempre teve acesso a todo afeto e atenção terapêutica necessários ao tratamento. Entretanto, quando sua homossexualidade latente transpareceu na adolescência, os mesmos pais que sempre o haviam cercado de carinho e compreensão reagiram com intolerância e vergonha. Ele teve de se afastar traumaticamente da família para conseguir vivenciar a plenitude de sua identidade sexual. Muitos anos depois, para tentar entender as relações entre essas duas identidades divergentes das expectativas dos pais, e como elas puderam provocar sentimentos tão antagônicos, o autor realizou uma abrangente pesquisa sobre o universo da diversidade em famílias com filhos marcados pela excepcionalidade. Surdos, anões, portadores de síndrome de Down, autistas, esquizofrênicos, portadores de deficiências múltiplas, crianças prodígios, filhos concebidos por estupro, transgêneros e menores infratores: dez “identidades horizontais” (isto é, divergentes dos padrões familiares, linguísticos e sociais predeterminados), sujeitas em graus distintos a influências genéticas e ambientais, compõem a constelação de temas deste magnífico tour de force sobre os sentidos de ser diferente e, principalmente, de aprender a amar e respeitar as diferenças.

Influence of the social context on use of surgical-lengthening and group-empowering coping strategies among people with dwarfism.

OBJECTIVE: To assess the role that social contextual factors exert on the way people with disproportionate short stature (dwarfism) cope with the negative consequences of discrimination. METHOD: Using multigroup structural equation modeling, we compare the coping process of people with dwarfism from Spain (N = 63) and the USA (N = 145), two countries that differ in the role played by organizations offering support to people with dwarfism. RESULTS: In Spain, where organizational support is recent, a coping approach aimed at achieving integration with the majority group through limb-lengthening surgery prevails; in the USA, where the long-standing organization of people with dwarfism encourages pride in being a "little person" and positive intragroup contact, a coping strategy based on empowering the minority group dominates. CONCLUSIONS: Both strategies, each in its own context, are effective at protecting psychological well-being from the negative consequences of stigmatization; however, they exert their positive effects through different processes.

Moyamoya-like vasculopathy and Seckel syndrome: just a coincidence?

INTRODUCTION: Seckel syndrome (SS) and other microcephalic primordial dwarfisms (MPDs) are a group of autosomal recessive disorders characterized by prenatal and postnatal growth retardation, microcephaly, and distinct facial dysmorphic features. There are an increasing number of reports in the literature linking MPDs with cerebrovascular anomalies, including intracranial aneurysms and moyamoya. CASE REPORT: An 18-year-old female patient with SS and mental retardation was referred for spontaneous subarachnoid hemorrhage. At the age of 3 years, she had suffered multifocal ischemic cerebrovascular accidents following an elective urological procedure. Cardiac, hematologic, and serologic workups were negative, and cerebral angiography was recommended but declined by the parents. Brain MRA and cerebral angiography showed bilateral narrowing of extracranial and intracranial internal carotid arteries (ICAs), obliteration of the right supraclinoid ICA without moya-moya collaterals, and multiple bilateral saccular aneurysms on the hypertrophied posterior cerebral arteries. Considering the patient's previous quality of life and the high risks of either endovascular or surgical treatment, all invasive treatments were withheld at the parents' request and only palliative care was offered. CONCLUSION: It appears that patients with MPD are prone to the development of cerebrovascular anomalies. Therefore, imaging of cerebral vessels should be performed when such patients present with cerebral ischemia or stroke.

Medical and social aspects of the life course for adults with a skeletal dysplasia: a review of current knowledge.

PURPOSE: The paper examines the general literature and available research evidence on medical, health and social aspects of life for adults with skeletal dysplasia conditions causing profound short stature. METHOD: The paper reports on a literature review using available medical, psychological and social sources. RESULTS: There is a dearth of methodologically sound research evidence in this field, and this is particularly marked in areas such as transition to adulthood, ageing and medical, surgical and health experiences. CONCLUSIONS: There are serious gaps in the available literature and research evidence is sparse and often based on biased samples of limited numbers. This means that it is difficult to get information beyond the anecdotal in assessing the health and social needs of this group of people, and in particular to define needs that are currently unmet. It also limits the scope of advice and information available to health professionals and others in the field who offer support to adults with the conditions and parents of newly-diagnosed babies and young children.

Adaptive skills, cognitive, and behavioral characteristics of Costello syndrome.

Costello syndrome is a rare congenital disorder whose diagnosis is based on clinical findings. The underlying genetic cause has not been identified. Common characteristics include failure to thrive, feeding problems, short stature, coarsening of facial features, developmental delay, mental retardation, skeletal problems, cardiac complications, and increased risk for solid tumors. Given its rarity, existing literature is limited regarding its natural course. Developmental milestones and intellectual functioning have never been systematically studied in this population, therefore this study focused on defining developmental and intellectual attributes. Data was obtained through solicited participation at the 3rd International Costello Syndrome Meeting. A total of 18 children (age 3-20 years) were administered the Leiter-R brief-IQ and the Peabody picture vocabulary test (PPVT)-III to assess nonverbal cognitive functioning and receptive vocabulary. Parents/guardians completed the child behavior checklist (CBCL) and participated in an interview process to complete the survey form of the Vineland adaptive behavior scales to assess emotional/behavioral issues and adaptive behavior. Results indicated that nonverbal cognitive functioning ranged from 1.5 to 4.3 SD below the age mean. Receptive vocabulary skills ranged from average functioning to 4 SD below the age mean. Adaptive behavior composites were all in the low range (2.0 to >5.0 SD below age mean), however there was significant variability in the range of domain scores. CBCL results ranged from normal to clinically significant across various clinical parameters. These data support a generalized descriptive pattern of developmental delay and mental retardation, with noted variability in receptive language, level of adaptive behavior functioning, and emotional/behavioral aspects. Skills and behavior are compared to existing literature of children with various syndromes.

Some psychosocial aspects of nonlethal chondrodysplasias: I. Assessment using a Life-Styles Questionnaire.

Studies concerning the psychosocial aspects of skeletal dysplasias that cause disproportionate short stature have been few and have usually involved small numbers of patients. As part of a study involving patients with chondrodysplasias and their families, an assessment battery of standardised instruments designed to measure depression, anxiety, self-esteem, personal support networks, marital adjustment, and family structure were completed by patients and, in many cases, their sibs, spouses, and/or parents. This first in a series of six papers reports the results of a Life-Styles Questionnaire which provides some insights into the levels of satisfaction with various aspects of life, including friendships, employment, the use of some substances and services, and the impact of the skeletal dysplasia on career, marriage, and childbearing. Results are presented for patients and the unaffected parents of patients. Overall, the study has shown a high level of satisfaction with many aspects of life. However, there are important differences in attitudes between the married and unmarried patients, and in some cases the unaffected parents, in a number of areas including health, overall satisfaction with life, and concerns surrounding child bearing and employment.

Some psychosocial aspects of nonlethal chondrodysplasias: IV. Dyadic scale of marital adjustment.

This article examines marital adjustment of couples who have had a child with dwarfism due to a skeletal dysplasia, and of couples where one or both members are dwarfs. The instrument used was the Dyadic Adjustment Scale developed by Spanier [1976: Marriage Family 38:15-38]. The reasons for examining this psychosocial aspect of dwarfism were that the birth of a dwarfed child to average-size parents might be expected to cause stress in the relationship, and because several authors had raised concerns about the nature and/or quality of marriages involving dwarfs. This study provides evidence of a decrease in the level of marital adjustment for the average-size parents of affected children, gives tentative reassurance about marriages where both individuals are dwarfs, but raises some concerns about couples where only one member is a dwarf.

Short stature at school entry--an index of social deprivation? (The Wessex Growth Study).

This study was carried out to examine the biological and environmental variables associated with non-organic short stature. We observed an unselected population of very short normal children (SN) and their age- and sex-matched controls (C) within the community. All 14,346 children in two health districts entering school during 2 consecutive years were screened for short stature, and those whose height lay below the 3rd centile, according to Tanner and Whitehouse standards (n = 180) were identified. Excluding 32 with pathology, five from ethnic minorities and three who refused to take part, the remaining SN children (mean height SDS-2.26) were matched with 140 age- and sex-matched controls (C) of average height (mean height SDs 0.14). Birth weight, target height and predicted adult height (based on parental height and bone age respectively), medical and social background (obtained from parental interviews), and school performance (assessed by class teachers) were the main outcome measures. Mean birth weight of the SN children was significantly lower than C (SN = 2845 g, C = 3337 g, P < 0.001). Mean mid-parental target height was also very different (SN = 162.0 cm, C = 170.9 cm, P < 0.001). Thirty-five per cent of SN children (C = 6%) had height SD scores below parental target range, though only 10% had predicted heights below target range (mean delay in bone age 0.68 years). There was a significant difference between SN children and C in the number of children in the household (SN = 2.8, C = 2.4 (P = 0.007) and in socio-economic status (P < 0.002). Many more SN children were in social classes IV and V (SN = 31%, C = 13%, P < 0.002), and had an unemployed father (SN = 22%, C = 10%, P < 0.010), highlighting the importance of environmental influences on growth. One in four SN children was judged to have serious psychosocial problems. However, the lower the socio-economic class, the less likely the SN children were to be inappropriately short for parents. Significantly more SN children were reported to have asthma (SN = 18%, C = 7%, P < 0.007) and eczema (SN = 19%, C = 5%, P < 0.001), though only the latter was significantly associated with stature below target height for both SN and C groups. Biological variables are often insufficient to explain short stature. No child, whatever the parental height, should be dismissed as normal without careful evaluation, as poor growth in the early years may be an important pointer to an adverse but potentially remediable environment.

Activity and behavioral development in stunted and nonstunted children and response to nutritional supplementation.

It is frequently assumed that undernutrition in young children leads to poor development through reduced activity. 3 groups of 26 1-year-old stunted children were studied: nutritional supplementation, supplementation with psychosocial stimulation, and controls. 26 nonstunted comparison children were also studied. Activity levels were measured by extensive observation in the homes, and development using 4 subscales of the Griffith's Mental Development Scales. Initially, stunted children were less active than nonstunted ones (p < .01), but after 6 months they caught up regardless of treatment. The mental ages of the stunted children were lower than those of the nonstunted children initially, and improved with either treatment. Initially, activity levels made a significant contribution to the variance in the locomotor subscale only, but not 6 months later. Activity did not predict change in development over 6 or 12 months, nor did change in activity over 6 months predict change in development over 12 months.

Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study.

Limited information is available on the educational and behavioral functioning of short children. Through 27 participating medical centers, we administered a battery of psychologic tests to 166 children referred for growth hormone (GH) treatment (5 to 16 years) who were below the third percentile for height (mean height = -2.7 SD). The sample consisted of 86 children with isolated growth-hormone deficiency (GHD) and 80 children with idiopathic short stature (ISS). Despite average intelligence, absence of significant family dysfunction, and advantaged social background, a large number of children had academic underachievement. Both groups showed significant discrepancy (p < .01) between IQ and achievement scores in reading (6%), spelling (10%), and arithmetic (13%) and a higher-than-expected rate of behavior problems (GHD, 12%, p < .0001; ISS, 10%, p < .0001). Behavior problems included elevated rates of internalizing behavior (e.g., anxiety, somatic complaints) and externalizing behavior (e.g., impulsive, distractable, attention-seeking). Social competence was reduced in school-related activities for GHD patients (6%, p < .03). The high frequency of underachievement, behavior problems, and reduced social competency in these children suggests that short stature itself may predispose them to some of their difficulties. Alternately, parents of short, underachieving children may be more likely to seek help. In addition, some problems may be caused by factors related to specific diagnoses.

Incidence of growth lines in psychosocial dwarfs and idiopathic hypopituitarism.

The presence of growth lines in the distal radius was evaluated prior to treatment in 23 psychosocial dwarfs and 25 patients with idiopathic hypopituitarism. The lines were very common in the psychosocial dwarfs and rare in the pituitary dwarfs (P = .0005). This finding can be explained by the fluctuating adverse environment to which the psychosocial dwarf is exposed and the constant lack of growth in hypopituitary patients. Therefore, in the absence of systemic disease, when growth lines are present in a patient with short stature or failure to thrive, a thorough review of the patient's psychosocial environment should be made.