Jaime L. Frias

Non-genetic risk factors for gastroschisis†‡§

Gastroschisis is an abdominal wall defect typically located to the right of the umbilical cord in which intestines and occasionally other abdominal contents herniate through the abdominal wall opening. The etiology of this defect is unknown. The increased recurrence risks observed in families with a child with gastroschisis suggest that genetic factors play a role in its causation. However, non‐genetic factors are also important, as evidenced by the increased occurrence of gastroschisis among younger mothers, the increasing prevalence of gastroschisis in recent years observed by several birth defects surveillance systems, and the frequent occurrence of gastroschisis in a cluster pattern. Despite recognition of the importance of non‐genetic factors in gastroschisis causation, no factors, other than young maternal age, have been definitively identified, limiting the development of prevention strategies. This article summarizes the currently available literature on non‐genetic risk factors for gastroschisis, including investigations of sociodemographic factors, maternal therapeutic medication and non‐therapeutic drug exposures, chemical exposures, and other factors. The article also discusses some of the challenges faced by investigators working to better understand gastroschisis etiology. Published 2008 Wiley‐Liss, Inc.

Menkes kinky hair syndrome: Is it a treatable disorder?

A male infant with Menkes Kinky Hair Syndrome was treated with a 3‐week course of cupric acetate infusions, which was terminated when he developed aminoaciduria. The lack of improvement seen in this infant is representative of the reported experience with parenteral copper therapy in this condition, and may be attributable to the presence of a clinically significant abnormality in copper metabolism in utero.

DIABETES MELLITUS, SHORT STATURE AND JOINT STIFFNESS — A NEW SYNDROME

Three unrelated patients, 2 boys 18 1/2 and 19 years old and a girl aged 17, have stable insulin-dependent diabetes mellitus, short stature and joint stiffness beginning 8 to 13 years after the onset of diabetes. The older boy, after 16 years of diabetes, has small retinal hemorrhages, hypertension, azotemia and proteinuria. The younger boy developed diabetes at 14 months, has punctate retinal hemorrhages with no proteinuria, and the girl has proteinuria but no retinal changes; neither of these 2 has azotemia or hypertension. Stature of the 2 boys, who have attained final height following a normal adolescent spurt, is 17 and 25 cm. less than that of their fathers. The girl has familial delayed maturation and is near the end of an adolescent growth spurt with predicted final height 14 cm. less than maternal stature. Joint stiffness involves limited extension and flexion of interphalangeal, meta-carpophalangeal, wrist and ankle in all 3, neck and trunk in 2, toes and elbows in 2 and knee and hip in one. The girl has pes cavus. There is no pain or disability and no progression of joint stiffness after the 6 months to 1 year period of its development. Slight but definite improvement in mobility has been noted in 2 during 2-3 years of follow-up study. Roentgenograms show no intrinsic or periarticular abnormalities. Skin is thickened and was unusually difficult to cut; biopsies were studied by light and electron microscopy and for collagen turnover in tissue culture.

Hypoimmunoglobulinemia with normal T cell function in female siblings

Abstract A distinct syndrome reported here provides evidence for an autosomal recessive counterpart to X-linked (Brutons) hypoimmunoglobulinemia. Two sisters had humoral (B cell) immunodeficiency. One suffered from recurrent infection, the second presented with non septic arthritis. Both had markedly lowered immunoglobulin levels in serum and secretions, deficient antibody production, and absent B-dependent regions in their lymph nodes. They also lacked surface immunoglobulin-bearing peripheral blood lymphocytes. T cell number and cell-mediated immunity were normal; lymphocytes with complement or Fc receptors were present.

Neuroradiology and clinical aspects of Usher syndrome

We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US 1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.

Sclerocornea Associated with the Smith-Lemli-Opitz Syndrome

A 2,000-g infant boy had many features of the Smith-Lemli-Opitz syndrome (prenatal growth deficiency and developmental retardation, microcephaly with unusual facies, hypospadias, and feeding difficulties) as well as sclerocornea. The association of this rare eye finding with this rare congenital syndrome is unique. Successful penetrating keratoplasty was performed in one eye at 8 months of age.

A cephalometric study of fetal alcohol syndrome

Analysis of cephalometric radiographs of 12 children with fetal alcohol syndrome corroborated the clinical observation of midfacial deficiency described in patients with this disorder. Contrary to previous reports, however, our data show that this abnormality is not caused by true maxillary hypoplasia but by retrusion of the maxilla. We postulate that this abnormal position is secondary to restricted forward growth of the face, resulting from abnormal brain growth and subsequent shortening of the anterior cranial base.

Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation

An 8‐year‐old female child with mental retardation (MR), multiple congenital anomalies (MCA) and irregular pigmentation was shown to have karyotypic mosaicism involving chromosome 14 abnormalities. Four cell lines were found in both peripheral blood lymphocytes and skin fibroblasts and were represented by: a normal karyotype, an isopseudodicentric 14q [iso psu dic(14)], a ring 14 [r(14)], and a monosomy 14 [mono(14)]. Our results are compared with reported cases involving multiple abnormalities of specific chromosomes. Karyotypic mosaicism of comparable chromosome 14 abnormalities is rare, with only one known previous case. Detailed analysis of karyotypic mosaicism of rare chromosomal abnormalities is essential to determine meaningful correlations with specific patterns of malformation.

A cephalometric study of the craniofacial skeleton in trichorhinophalangeal syndrome

A prominent feature of the trichorhinophalangeal syndrome is a very characteristic facies. This study quantitates differences in craniofacial skeleton between affected and unaffected members of the same kindred. Standard scores for various measurements taken from lateral cephalometric radiographs were compared for statistical significance, and these were further correlated with similar data calculated from length measurements of the middle phalanx of the second digit. The affected group had a shortened posterior face height (p less than 0.01) associated with a short mandibular ramus (p less than 0.01) as well as a reduced and superiorly deflected posterior cranial base (p less than 0.01). These craniofacial changes result in a steep inclination of the lower border of the mandible (p less than 0.01) and suggest disturbances in the epiphyseal growth sites of the skull as demonstrated by a high degree of correlation between the dysplasia of the cranial base, shortening of the posterior portion of the face, and shortening of the middle phalanx of the second digit.

Spondylometaphyseal Dysplasia: A Variant Form

Spondylometaphyseal dysplasia (SMD), a heterogeneous group of chondro-osseous dysplasias with combined vertebral and metaphyseal abnormalities, is being recognized and reported more frequently. The cumulative experience with these patients suggests that the Kozlowski type of SMD is a distinct form, and transmitted as an autosomal dominant. Many other forms of SMD exist which, as yet, cannot be completely classified. A father and daughter who demonstrate a variant form of SMD, both with absence of the odontoid processes, are described and their place in the spectrum of this group of diseases is discussed.