The role of genetic counseling in visually impaired adolescents.

The presence of genetic disorders in a high percentage of adolescents with significant visual impairments emphasizes the important role that genetic counseling can play in this population. However, its intended goals have been controversial. Responses to structured interviews about genetic counseling services from three groups of former students from the Kentucky School for the Blind were compared. One group consisted of students who had received genetic counseling; another, of students who had declined it; and a third, of students who had graduated before the service was available. In all groups, genetic counseling was viewed as a valuable service which would have been pursued by the majority of those who did not have the opportunity to receive it, and by many of those who refused it initially. Although genetic counseling did little to enhance knowledge of the cause of the specific visual impairment, it appeared to be useful in providing information regarding the risk of visual impairment in future offspring. A relatively high rate of unplanned pregnancies was noted in the group who had refused genetic counseling. The significance of this observation is uncertain. One interpretation is that the group refusing genetic counseling may have consisted of individuals who had fewer concerns as adolescents about family planning issues. These observations suggest that it may be appropriate to recommend to adolescents with significant visual impairments to defer childbearing until independent life experiences are accumulated outside the school setting. Then, prior to considering childbearing, genetic counseling should be sought.

Ivemark's "asplenia" syndrome: a single gene disorder.

Congenital heart defects as a group represent a significant proportion of congenital malformations. Most are isolated and multifactorially determined; a relatively small proportion are due to a single gene defect, and result in an increased risk of recurrence among first-degree relatives. We have reported the cases of three male siblings with Ivemark's "asplenia" syndrome to support an autosomal recessive mode of inheritance. We have stressed the importance of early recognition of mendelian disorders with associated cardiac malformations to provide meaningful counseling regarding prognosis, medical management, and risk of recurrence.

The physician under Public Law 99-457.

Public Law 99-457, enacted in 1986, reauthorizes P.L. 94-142 (the Education of all Handicapped Children's Act of 1975) and extends the mandate of that earlier legislation to all handicapped children ages 3 to 5. In addition, P.L. 99-457 provides for early intervention services for handicapped children from birth to age 2. While the implementation of P.L. 94-142 has been conducted primarily within a traditional educational framework, the provision of services to younger children, especially to the birth to age 2 handicapped population, will require the active participation of the medical community. This paper reviews the major provisions of P.L. 99-457, discusses how the legislation will likely translate into the provision of services, and outlines some of the more immediate implications of the law for the management of children's developmental disorders by the medical community.

A terminal deletion (14)(q31.1) in a child with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and mild mental retardation.

A female child with a terminal deletion on the long arm of chromosome 14, 46,XX,del(14)(q31.1), presented with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and a small haemangioma on the back. She was mildly mentally retarded. Only a few patients with a partial deletion of 14q (14q-) have been reported without consistent clinical findings. Although a clinical syndrome associated with ring chromosome 14, r(14), has been established, no distinct pattern has been so far reported in 14q-.

Mild intellectual deficits in a child with 49,XXXXY.

Severe mental retardation usually is present in males with a 49,XXXXY karyotype, although occasionally, intellectual functioning has been reported to be in the mild range of mental retardation. One child was previously described to have normal development at 15 months, but had mental retardation at 41 months. We present a male with 49,XXXXY who had mild-cognitive and motor delays and age-appropriate adaptive skills at 59 months. Greatest deficits were in expressive verbalizations similar to other male sex chromosome abnormalities. Mosaicism could not be demonstrated in blood or skin specimens. Although most males with 49,XXXXY syndrome will have significant mental retardation, findings in our patient and other reports suggest that variability in intellectual functioning may occur, in some instances, and may justify guarded optimism in affected males demonstrating close to or age-appropriate developmental skills through early childhood.

Does a supernumerary nipple/renal field defect exist?

In 65 patients evaluated for suspected genetic and/or developmental problems, a roentgenographic study of the kidneys was performed because of the presence of a supernumerary nipple (SNN). Seven of 65 (11%) had a significant renal lesion that included conjoined kidneys in a female with Fanconi's anemia. Four of these patients did not have signs or symptoms suggestive of an underlying urinary tract pathologic condition. These results indicate that an SNN/renal field defect probably exists, although the significance of this association is significantly weaker than that originally proposed by Mehes. One variable influencing this association appears to be racial differences, as evidenced by the absence of renal defects in blacks with an SNN. Based on our findings, the identification of additional minor phenotypic abnormalities may represent an additional mediating variable in this association. However, the discovery of an SNN in an otherwise normal individual, or an individual with a recognizable pattern of human malformation not associated with renal anomalies or central nervous system dysfunction alone, does not appear to be an indication for additional diagnostic studies of the urinary tract.

Familial iridoplegia.

Fixed, dilated pupils in childhood are usually due to interruption of parasympathetic innervation as a result of neurologic impairments or occur following pharmacologic mydriasis. We present a familial form of iridoplegia without structural defects of the eye which is consistent with a probable autosomal dominant mode of inheritance. Examination of other family members should be part of an affected individual's evaluation particularly when this finding occurs as an isolated defect. Recognition of such an entity may avoid unnecessary neurodiagnostic studies in an affected individual.

Computed tomography of the head in the evaluation of microcephaly.

Eighty-five infants and children found to have microcephaly had computed tomographic (CT) brain scans performed. A greater degree of microcephaly correlated with the finding of atrophy or ventricular dilation on CT scan. Patients who had known preceding destructive brain insults had the highest incidence of abnormal findings on scans (20/22). Patients who had CNS dysfunction of unknown etiology had the lowest frequency of abnormal findings (12/33); however, in three of these patients, a previously unsuspected brain malformation was found on CT scan. Patients who had other congenital anomalies had an intermediate proportion of abnormal findings on CT scans (20/30), and in 11 of these scans, a previously unsuspected or only partly suspected brain malformation was diagnosed. Discovering previously unsuspected information or finding supportive data regarding the basis for the underlying disease process, being able to provide a more specific developmental prognosis and accurate genetic counseling, justifies the inclusion of a CT scan of the head in the evaluation of the microcephalic child.

Clinical correlations in partial hypoxanthine guanine phosphoribosyltransferase deficiency.

Erythrocyte assays for hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity performed on two male half-siblings with hyperuricemia, produced results consistent with classic Lesch-Nyhan syndrome. Due to the absence of neurologic abnormalities, cognitive deficits, or self-mutilation, HGPRT activity was measured by intact fibroblast assay which revealed partial enzyme deficiency. The presence of an unstable mutant enzyme may have led to the discrepancy between the erythrocyte and fibroblast studies. This discrepancy emphasizes the difficulty in assaying this enzyme solely utilizing red blood cell studies to determine a patient's course. In order to provide an accurate prognosis and relevant genetic counseling, measurement of this enzyme utilizing intact fibroblasts is critical after establishing a diagnosis of HGPRT deficiency in a hyperuricemic male lacking typical clinical manifestations of Lesch-Nyhan syndrome, but having enzyme activity of erythrocytes consistent with the diagnosis.

Townes syndrome. A distinct multiple malformation syndrome resembling VACTERL association.

An 8-year-old male is presented with clinical findings of Townes syndrome in an otherwise unaffected family. Additional abnormalities possibly representing low frequency associations of this autosomal dominant multiple malformation syndrome included a cardiac defect and hypospadias. Similarities exist between Townes syndrome and VACTERL association, which is generally regarded to be sporadic in nature. Recognition of Townes syndrome as a distinct entity is critical for implementing appropriate management in early childhood, including amplification of hearing impairments. Variable expressivity may occur in this disorder. Careful evaluation must be made, therefore, of the parents of an affected infant with an apparent sporadic case, in order to provide the couple with an accurate recurrence risk at genetic counseling.

Toluene embryopathy.

Three children with microcephaly, central nervous system dysfunction, minor craniofacial and limb anomalies, and variable growth deficiency were born to women who inhaled large quantities of pure toluene throughout pregnancy. The features in our patients were reminiscent of the patterns of malformation previously described following in utero exposure to alcohol, certain anticonvulsants, and hyperphenylalaninemia. It is possible that there is a variable and nonspecific teratogenic phenotype characterized by alterations in growth, development, and morphogenesis. Careful evaluation and monitoring of infants exposed to toluene in utero are needed to determine the significance of our findings.

Sternal malformation/vascular dysplasia association.

Sternal defects associated with superficial craniofacial vascular lesions are rare. We report on two additional patients with a sternal cleft and cutaneous, craniofacial hemangiomata to emphasize that this unusual combination of findings represents a recognizable sternal malformation/vascular dysplasia association. In addition, internal vascular lesions were also identified in these individuals, in one instance involving the upper respiratory tract and in the other the viscera. Although the pathogenesis of these findings is unclear, an early disturbance affecting midline mesodermal structures leading to lack of complete fusion of lateral sternal bands and overlying cutaneous tissue, or deficient formation of a proposed medioventral unpaired structure which may be involved in the formation of the sternum, and persistence and proliferation of midline angioblastic tissue may be possible mechanisms during the sixth to ninth gestational weeks. To date, all but one of the 15 known cases have been sporadic and no teratogen has been identified as a cause for these clinical manifestations. The presence of this association should signal the need to search for potentially life-threatening internal hemangiomata.

Dup(4p)del(9p) in a familial mental retardation syndrome. Resemblance to de Lange syndrome detected by high-resolution banding.

A young woman with features resembling de Lange syndrome had a normal banded karyotype. Similar phenotypes were present in a maternal aunt and uncle. Utilizing high-resolution banding, the propositus was found to have a chromosomal abnormality characterized by dup(4p)del(9p). Using the same banding technique, her mother and two of her siblings were identified as having balanced reciprocal translocations. Chromosome studies with high-resolution banding should be performed in these instances even in the presence of a normal banded karyotype. Determining a chromosomal basis for the phenotype may lead to a significant reproductive risk in individuals with balanced chromosomal rearrangements and may afford them with the opportunity to pursue prenatal diagnosis.

Forearm fullness in Coffin-Lowry syndrome: a misleading yet possible early diagnostic clue.

Two unrelated infants with delayed development and suspected abnormalities of the upper limbs were found to have the Coffin-Lowry syndrome. Both had marked fullness of the forearms in the presence of normal skeletal structures which resulted from increased subcutaneous fat. Although initially misleading, the forearm changes may serve as an early diagnostic clue in this disorder.

Cognition in cerebral gigantism: are the estimates of mental retardation too high?

The psychological findings on 10 children with cerebral gigantism are reviewed. Infants with cerebral gigantism showed a consistent pattern of psychomotor delay. Preschool age children demonstrated signs of a primary language disorder, and school-age patients had learning disabilities. The incidence of mental retardation was significantly lower than previously reported in the literature. The possibility that some children with cerebral gigantism can be easily misdiagnosed as mentally retarded is discussed.