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We describe 3 sibs (2 males and 1 female) with multiple congenital anomalies, poor growth, seizures, and progressive central nervous system (CNS) degeneration leading to death in infancy. Radiographic changes in all 3 were similar, and included moderate shortness of long bones, platyspondyly, and hypoplastic pelvis. Autopsies showed diffuse encephalomyelopathy and enlargement of the lateral and third ventricles. Lysosomal enzyme activities were normal. Collagen type II analysis on 2 of the sibs indicated normal collagen. Chromosomes appeared normal. Even though the radiographic and chondroosseous morphologic findings in these sibs have a certain similarity to Dyggve-Melchior-Clausen syndrome, their clinical course does not fit this condition. These infants appear to represent a new syndrome of bone dysplasia and CNS degeneration inherited as an autosomal recessive trait.

We present the findings of 13 additional cases of the urorectal septum malformation (URSM) sequence, and review the literature. The URSM sequence consists of ambiguous genitalia concurrent with absence of perineal and anal openings. The sex ratio of the 13 new cases was 7 males to 6 females and from the literature 21 males and 28 females. In addition, 11 of the 13 new cases had anorectal atresia with 5 of the cases also having partial agenesis of the colon. Bilateral renal agenesis was present in 3 of the 13 cases, unilateral renal agenesis occurred in 6, and dysplastic kidneys were found in 10. The URSM sequence is a lethal condition with long-term survival reported in only 3 of a total of 62 literature and new cases. Recurrence of this condition has not been reported.

We describe 13 unrelated children with abnormalities of somatic growth, face, brain, and connective tissue including vasculature. Although the condition in these children falls under the general group of disorders known as cutis marmorata telangiectatica congenita (CMTC), the constellation of abnormalities appears to constitute a distinct and easily recognizable phenotype within this general group. In contrast to most children reported with CMTC, children in this subgroup have a high risk for neurologic abnormalities, including developmental delay, mental retardation, megalencephaly, and hydrocephalus. Early recognition of this condition is important for appropriate surveillance for known complications and parental counseling.

Patients with the RSH or Smith-Lemli-Optiz syndrome (SLOS) have an inborn error of cholesterol biosynthesis which results in a deficiency of cholesterol and an elevation of the cholesterol precursor, 7-dehydrocholesterol. A treatment protocol consisting of administration of cholesterol +/- bile acids was initiated in an attempt to correct the biochemical abnormalities seen. Fourteen patients (8 female, 6 male: ages 2 months to 15 years) have now been treated for 6-15 months. Three patients received cholesterol alone, while 11 patients received cholesterol and one or more bile acids. Biochemical improvement in sterol levels and in the ratio of cholesterol to total sterols was noted in all patients. The most marked improvement was noted in patients presenting with initial cholesterol levels < 40 mg/dl. No toxicity was observed. Clinical improvement in growth and neurodevelopmental status was also observed.

We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX, -21/46, XX, -21, +r(21), who has limited manifestations of Down syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a hematologic disorder particularly common in Down syndrome patients. In situ hybridization studies, gene dosage, and DNA polymorphism analysis showed that the ring chromosome carries a duplicated region which extends from D21S406 on the centromeric side and includes marker D21S3 on the telomeric side. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) probably was formed postzygotically. Included in the duplicated segment are the candidate genes for leukemia AML-1, ETS, and ERG. The potential significance of disomic homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed.

Gastroesophageal abnormalities occur with increased frequency in patients with Brachmann-de Lange syndrome (BDLS) and contribute to problems with feeding, emesis and failure to thrive. Comprehensive evaluation including longitudinal assessment of growth and development of 8 patients with BDLS was performed. Clinically significant feeding problems occurred in 6 of the 8 patients and the affected children were subsequently evaluated for gastrointestinal abnormalities. Findings in these patients included tracheal aspiration, esophageal dysmotility, gastroesophageal reflux, hiatal hernia, and esophagitis. Medical treatment was instituted where appropriate, and surgical treatment was performed if the problems did not resolve with medical treatment. Improvement in weight centiles occurred in all patients fed by nasogastric or feeding gastrostomy tube but only one patient appeared to experience increase in rate of linear growth. Careful monitoring of symptoms and growth parameters, and prompt institution of appropriate medical and surgical measures can improve the health and physical outcome of many patients with BDLS.

Absence of the kidneys and of the Müllerian structures has been reported in many patients. We report on a brother and sister, born to nonconsanguineous parents, with renal hypoplasia, Müllerian duct hypoplasia, and strikingly similar facial abnormalities. Both sibs have severe growth and developmental retardation. We think that the unique clinical findings in these sibs represent a new syndrome. The embryological and genetic implications of this condition are discussed.

An infant was found to have the previously known manifestations of the Kaufman syndrome (hydrometrocolpos, postaxial polydactyly, and congenital heart disease) but also imperforate anus, malrotation of gut, congenital hip dislocation, and urogenital sinus. All of these anomalies have been separately reported in other cases of the syndrome. Three previously unreported problems present in this case were choanal atresia, pituitary dysplasia, and vertebral anomalies; these may well be component manifestations of the syndrome and not sporadic occurrences in our patient. Of particular clinical importance were the hypoglucocorticism and the hypoglucocorticism secondary to the pituitary dysplasia.

The Antley-Bixler syndrome (ABS) is characterized by craniosynostosis, radiohumeral synostosis, and femoral bowing. Other findings include a trapezoid-shaped head, deformed ears, severe midface hypoplasia, choanal atresia or stenosis, and long bone fractures. Most ABS cases have died in the first months of life from respiratory complications. The poor prognosis in this condition makes counseling difficult and early termination of pregnancy a consideration. The medical and surgical management information presented here can be used as a guide for counseling parents in the future. We report on a new patient with ABS who now at age 3 yr, has been followed by the medical staff of Riley Children's Hospital since birth. She has had successful medical and surgical management. Although the multisynostoses seen in this disorder is undoubtedly related to the soft tissue malformations such as choanal stenosis and midface hypoplasia, the cause remains unknown. The literature is also reviewed in this condition.

Three infants are reported with a recognizable pattern of defects consisting of severe microcephaly, overlapping sutures, prominence of the occipital bone, and scalp rugae. This condition, which we think represents microhydranencephaly, appears to be produced by partial brain destruction during the second or third trimester, diminution in intracranial hydrostatic pressure, and subsequent collapse of the fetal skull. Several different causes for this condition have been suggested including partial disruption of the blood supply to the brain and prenatal viral infection.