Sporadic case of apparent aprosencephaly.

We report a sporadic case of apparent aprosencephaly, ie, apparent absence of forebrain with the facial anomalies of the (alobar) holoprosencephaly field complex. The infant lived-14 months, manifested temperature variations between 34.5 and 41.7 degrees C, and suffered at least one episode of severe hyponatremia suggesting hypoaldosteronism of brain or adrenal origin. Eye changes were suggestive of Rieger mesodermal dysgenesis.

Studies of malformation syndromes of humans XXXIIIC: the FG syndrome - further studies on three affected individuals from the FG family.

The brain findings at autopsy of an 18-year-old male with FG syndrome were megalencephaly, midline fusion of mammillary bodies, heterotopia of neuroglial tissue in the 7th and 8th nerves, and ependymal cell replacement by neuroglial tissue as well as a diffuse defect of neuronal cell migration evidenced from pachygyria of many gyri, dysgenesis of cerebral cortex, and heterotopia of neurons in the white matter of the centrum ovale. A cousin, studied at 20 weeks' gestational age, had gross turridolichocephaly with enlarged cranium and also multiple minor external and internal anomalies. An affected brother of this fetus died at 17 months of complications of a congenital heart defect and CNS dysfunction. X-linked inheritance of the FG syndrome is confirmed.

Isochromosome 12p mosaicism (Pallister mosaic aneuploidy or Pallister-Killian syndrome): report of 11 cases.

We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the isochromosome is usually absent in cultured lymphocytes but present in fibroblasts. The patients range in age from a 22-week-gestation fetus to a 45-year-old man. They have a distinct pattern of anomalies which enables one to make a diagnosis based on clinical manifestations alone. Craniofacial manifestations include "coarse" face with prominent forehead, sparsity of scalp hair, hypertelorism, epicanthal folds, flat bridge of nose, and highly arched palate. Affected newborn infants are profoundly hypotonic with sparsity of scalp hair especially bitemporally and a prominent forehead. Most have accessory nipples. Birthweight and growth parameters are usually normal; however, some newborn infants are unusually large. In infancy, the facial appearance becomes "coarse," hypotonia persists, and seizures may occur. As adults, growth may be normal, scalp hair is thicker and the mandible becomes prominent. Most have a generalized pigmentary dysplasia which may be evident with a Wood's lamp only. All cases have been sporadic and there is no consistent pattern of advanced parental age.

The dup(3q) syndrome: report of eight cases and review of the literature.

Clinical and cytogenetic examinations were performed on eight unrelated infants with duplication of part of the long arm of chromosome 3. A review of published cases shows a clinical syndrome characterized by statomotoric retardation, shortened life span, and a multiple congenital anomalies (MCA) syndrome of abnormal head configuration, hypertrichosis, hypertelorism, ocular anomalies, anteverted nostrils, long philtrum, maxillary prognathia, down-turned corners of the mouth, highly arched or cleft plate, micrognathia, malformed auricles, short, webbed neck, clinodactyly, simian crease, talipes, and congenital heart disease. The dup(3q) syndrome is a clinically easily recognizable entity.

Urinary levels of blood group A trisaccharide: observations in two siblings with neuronal ceroid lipofuscinosis.

A readily detectable carbohydrate in the urine of two siblings with neuronal ceroid lipofuscinosis was found to be the blood group A trisaccharide. One child expired before blood typing was done while the other sibling was AB. This latter child excreted greater amounts of the trisaccharide than a group of blood type A subjects with different diagnoses when all the subjects were receiving whole or skim milk by nasogastric feedings. While the relevance of this observation to neuronal ceroid lipofuscinosis is unknown, it has been shown that the trisaccharide may be a major urinary carbohydrate depending on diet and blood type.

Improved selenium, carnitine and taurine status in an enterally fed population.

Ten adult, male, nonambulant and gastrostomy-fed individuals had received commercially available enteral feedings containing negligible amounts of selenium, carnitine, and taurine for an average of 59 months. Blood levels of these three nutrients were below published normal ranges as were the urinary excretions of carnitine and taurine. After 9 weeks on a product that was fortified with 23 micrograms of selenium, 39 mg of carnitine, and 38 mg of taurine per 8 ounces, blood levels were significantly increased with the levels of selenium and carnitine being normalized.

Bone status in nonambulant, epileptic, institutionalized youth. Improvement with vitamin D therapy.

This study was conducted to determine if the adverse effects of anticonvulsant drug therapy and nonambulancy on bone status could be overcome with vitamin D therapy in severely handicapped individuals. Six male and five female gastrostomy fed, nonambulant, epileptic, profoundly mentally retarded individuals ranging in age from 7 to 17 years were given vitamin D therapy at a dosage of 4,000 IU/m2 body surface area/day for 6 months. Photon absorptiometry and biochemical indices of bone status were measured to follow the effects of therapy. Bone mineral content expressed as a percentage of normal improved by 11 percent (p less than 0.01), from 59.6 to 66.1 percent. Tartrate-resistant acid phosphatase, total alkaline phosphatase, and the bone isoenzyme activities declined 11 percent, 18 percent, and 11 percent respectively. These reductions were not statistically significant but they were consistent with the improvements observed by photon absorptiometry. The results of our study suggest that a conservative supplement of vitamin D will improve the bone status of severely disabled youths.

Rett syndrome at an institution for the developmentally disabled.

Rett syndrome (RS) is a condition apparently limited to females characterized by normal early development followed by the abrupt loss of acquired function and beginning autistic behavior in late infancy. Manifestations in RS include decelerating head growth, unusual "hand-writing" movements, gait apraxia, neuromuscular tone disturbance, and seizures. No biochemical, hematologic, cytologic, or cytogenetic procedures have been shown to confirm the diagnosis of RS. With the exception of one family with 2 affected half-sisters, all cases have been sporadic. Six profoundly retarded residents of Central Wisconsin Center have manifestations of RS. Three are microcephalic and 3 have head circumferences at or below the 10th centile. All have seizures or abnormal EEG findings and all were ascertained on the basis of characteristic hand movements. No case of precocious puberty was observed. Two patients had severe scoliosis which was surgically treated. Detailed neuropathologic examination should be sought for every case of RS. The development of clearly defined minimal diagnostic criteria and the establishment of an international registry are desirable.

The influence of nutrition on IGF-1 in tube-fed profoundly retarded adults.

OBJECTIVE: This study was conducted to determine whether IGF-I concentrations are low in nonambulant profoundly retarded adults and to identify associated nutritional factors. METHODS: Serum IGF-I, albumin, pre-albumin, creatinine, zinc (Zn) and plasma amino acids were measured before and after a four-week 25% increase in formula in 25 individuals, divided into those fed by day (Group A) or by night (Group B). RESULTS: Circulating IGF-I was low in nine of the 22 subjects (40.9%) included in the analysis. Mean IGF-I increased 10.4% (p=0.004). Despite high intakes of essential amino acids and Zn, initial mean plasma tryptophan and phenylalanine were low, and serum Zn was low in 40.9% of subjects. Plasma tryptophan was low at both samplings and correlated with circulating IGF-I concentrations (p=0.02) at the beginning of the study. Serum IGF-I and Zn also correlated (p=0.02) initially. CONCLUSIONS: IGF-I is commonly low in this population and is associated with low plasma amino acid and Zn concentrations, despite high intakes of these nutrients. The causes and clinical implications of these abnormalities need further study.

A prospective randomized double-blind study of gastroesophageal reflux surgery in pediatric-sized developmentally disabled patients: Nissen fundoplication versus Angelchik prosthesis.

In order to compare the standard Nissen fundoplication with the more recent Angelchik antireflux prosthesis, 47 pediatric-sized, developmentally disabled patients were prospectively randomized to receive either of these gastroesophageal antireflux procedures. The two groups were comparable at the time of surgery with regard to age, weight, surface area, emesis, number of chest radiographs, medications, lower esophageal sphincter pressure, and number and duration of reflux episodes during standard acid reflux testing. The Angelchik group required significantly less anesthesia time than the Nissen group: 107.4 +/- 22.6 min (mean +/- SD) versus 156.5 +/- 42.4 min (p less than 0.001). There was no difference in length of postsurgical hospital stay. Six months after surgery, both groups showed improvement. There was no significant difference between the Angelchik and Nissen groups in mean subjective assessment score, increased weight gain, decreases in emesis, numbers of chest radiographs, hospital days, or medications, increased lower esophageal sphincter pressure, or decreased numbers and duration of reflux during acid reflux testing. Long-term follow-up of eight Angelchik and 10 Nissen patients 12-30 months postsurgery (Angelchik 21.6 +/- 6.0 months, Nissen 21.9 +/- 5.0 months) demonstrated no significant difference in the percent of time the distal esophageal pH was below 4.0. Significant complications potentially related to the type of procedure developed in 1/21 patients in the Angelchik group and 1/17 patients in the Nissen group. We conclude that both procedures are usually effective for the surgical treatment of gastroesophageal reflux. Further study is indicated in order to establish the long-term superiority of one procedure.

A comparison of laboratory and clinical methods for diagnosing pertussis in an outbreak in a facility for the developmentally disabled.

During a pertussis outbreak in a facility for the developmentally disabled, culture- or direct fluorescent-antibody-confirmed cases were identified in 24 residents and 17 staff members; 38 (93%) were culture positive for Bordetella pertussis. An enzyme-linked immunosorbent assay (ELISA) was used to detect serum IgG and IgA to the filamentous hemagglutinin and lymphocytosis-promoting factor of B. pertussis. Using criteria from ELISA values, we identified an additional 83 residents and 28 staff members as seropositive. Among seropositive persons, antibody levels were elevated by the time of onset of respiratory symptoms and, in three of the four assays, remained elevated for 14 mo. In 44 seropositive persons tested within two weeks of onset of symptoms, 80% were culture positive, compared with 33% of 15 tested two to four weeks after onset (P = .003) and none of 15 tested more than four weeks after onset. The most specific (94%) clinical case definition identified only 41% of seropositive persons. Thus, ELISAs are important tools for individual diagnosis and epidemiological studies of pertussis.

Evidence for a high attack rate and efficacy of erythromycin prophylaxis in a pertussis outbreak in a facility for the developmentally disabled.

During an outbreak of pertussis in residents and staff of a facility for the developmentally disabled, 149 persons had laboratory evidence of Bordetella pertussis infection; 130 (87%) reported respiratory illness. Infection rates (IR) in affected wards ranged from 6% to 91%. Most residents were adolescents and adults and had received a full course of diphtheria-tetanus toxoids-pertussis (DTP) vaccine; IRs increased with increasing time after the last DTP dose in fully vaccinated residents. The IR was lower in residents on wards where erythromycin treatment/prophylaxis was started two or fewer weeks after the onset of illness in the first case on the ward (IR, 16%), compared with four or more weeks after onset (IR, 75%; P less than 10(-6)). Respiratory symptoms were milder in ill residents treated within seven days of onset of illness. Although B. pertussis transmission was substantial, erythromycin treatment of patients and prophylaxis of exposed persons was effective in decreasing transmission and disease severity. Carbamazepine toxicity occurred in seven (19%) of 37 residents when carbamazepine was administered with erythromycin.

LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.

In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.