Diagnostic yield of the comprehensive assessment of developmental delay/mental retardation in an institute of child neuropsychiatry

Abstract

The Consensus Conference of the American College of Medical Genetics has established guidelines regarding the evaluation of patients with mental retardation (MR) [Curry et al., Am. J. Med. Genet. 72:468-477, 1997]. They emphasized the high diagnostic utility of cytogenetic studies and of neuroimaging in certain clinical settings. However, data on the diagnostic yield of these studies in well-characterized populations of individuals with MR are scant. Majnemer and Shevell [J. Pediatr. 127:193-199, 1995] attained a diagnostic yield of 63%. However, this study included only 60 patients and the classification included pathogenetic and causal groups. The Stella Maris Institute has evaluated systematically patients with developmental delay (DD)/MR and performed various laboratory studies and neuroimaging in almost all patients. We report a retrospective analysis of the diagnostic yield of 120 consecutive patients observed at our Institute during the first 6 months of 1996. There were 77 males and 43 females; 47 were mildly delayed (IQ 70-50), 31 were moderately delayed (IQ 50-35), and 42 were severely delayed (IQ 35-20). Diagnostic studies (history, physical examination, standard cytogenetics, fragile X testing, molecular studies, electroencephalography, electromyography, nerve conduction studies, neuroimaging, and metabolic screening tests) yielded a causal diagnosis in 50 (41.6%) and a pathogenetic diagnosis in 47 (39.2%) of the 120 patients. Causal categories included chromosomal abnormalities (14), Fra(X) syndromes (4), known MCA/MR syndromes (19), fetal environmental syndromes (1), neurometabolic (3) disorders, neurocutaneous (3) disorders, hypoxic-ischemic encephalopathy (3), other encephalopathies (1), and congenital bilateral perisylvian syndrome (2). Pathogenetic categories included idiopathic MCA/MR syndromes (35), epileptic syndromes (10), and isolated lissencephaly sequence (2). Diagnostic yield did not differ across categories and degree of DD. Our results, while confirming the diagnostic utility of cytogenetic/molecular genetic, and neuroimaging studies, suggest the usefulness of accurate electroencephalogram recordings, and stress the importance of a thorough physical examination. Referral to a university child neurology and psychiatry service, where a comprehensive assessment with a selected battery of investigations is possible, yields etiologic findings in a high percentage of DD/MR patients, with important implications for management, prognosis and recurrence risk estimate.

Aetiology of intellectual disability in paediatric outpatients in Northern India

“…This proportion of diagnostic success compares well with studies conducted in wellequipped Western centres, where it has varied from 27 to 61%. 7,[27][28][29] Some of these studies have focused only on 'idiopathic' intellectual disability or GDD, which would explain the lower yield. Others have included all children presenting with intellectual disability or GDD, but settings such as theirs are likely to have a higher proportion of genetic cases.…”

“…Studies from industrialized countries have consistently shown that prenatal and genetic causes predominate. [6][7][8][9] Systematic Indian studies of this depth are lacking but literature from Turkey, 10 Pakistan, 11 Taiwan, 12 and China, 13 have also shown predominance of prenatal aetiology.…”

American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation

“…Mental retardation (MR), defined by the World Health Organization (WHO) as an intelligence quotient (IQ) < 70, is characterized by significantly limited cognitive functioning, coupled with limitations in adaptive skills in two or more of the following areas: social skills, community living, communication, home living, health, self-direction, work, and leisure 1,2. MR is generally divided into mild (IQ of 50–70), moderate (IQ of 35–50), and severe (IQ of 20–35); those cases in which the IQ is below 20 are occasionally defined as profound 2,3.…”

“…MR is generally divided into mild (IQ of 50–70), moderate (IQ of 35–50), and severe (IQ of 20–35); those cases in which the IQ is below 20 are occasionally defined as profound 2,3. The prevalence rate of MR in the general population is estimated to be approximately 1% to 3%, with mild MR occurring 7–10 times more frequently than moderate or severe MR 2,4,5…”

Caracterización citogenético molecular de enfermedades genéticas en el Hospital Base de Puerto Montt

“…Considerando que las aberraciones cromosómicas son la principal causa etiológica de DI, especialmente en los grados moderado a severo, es que el DI es otra de las principales indicaciones para análisis cromosómico y búsqueda de mutaciones relativamente frecuentes, como las responsables de los síndromes X frágil, Prader Willi y Angelman, entre otros. Identifi car la etiología de estas alteraciones permite el inicio precoz del manejo clínico adecuado, la estimulación sensorial y motora dirigida; además conocer el pronóstico y riesgo de recurrencia de la afección, así como también poder entregar asesoría genética reproductiva oportuna a los padres y otros familiares a riesgo [16][17][18] .…”