Chromosome 3p25 deletion in mother and daughter with minimal phenotypic effect.

3p25 deletion syndrome is characterized by mental retardation, growth retardation, hypotonia, microcephaly, ptosis, and micrognathia. Of the 42 persons with this deletion syndrome cited in the literature, only 2 patients, a mother-daughter pair, have previously been reported without apparent clinical consequence. We present a second mother-daughter dyad with a terminal 3p25.

Omphalocele and gastroschisis: an 18-year review study.

Purpose: Using data from a single University Genetics Division practice, the authors sought to determine if gastroschisis is increasing in occurrence compared to omphalocele. Associated abnormalities were also examined. In addition, prenatal exposure to teratogens and other parameters were compared.

Pontine hypoplasia in Carey-Fineman-Ziter (CFZ) syndrome.

We describe an infant with multiple congenital anomalies including cleft palate and micrognathia, Möbius sequence, developmental delay, myopathy, hydronephrosis, and bilateral clubfeet. These features are consistent with Carey-Fineman-Ziter (CFZ) syndrome (MIM 254940), which has been previously reported in six children (including two sibling pairs). Cranial magnetic resonance imaging (MRI) revealed an unusually small pons, a finding not previously described in CFZ syndrome.

Three cell line mosaicism involving structural and numerical abnormalities of chromosome 18 in a 3.5-year-old girl: 47,XX,+18/47,XX,+del(18)(q22)/46,XX.

We report on a 3.5-year-old girl with a mosaic karyotype including full trisomy 18, normal cells and a majority of cells with partial trisomy involving an extra chromosome 18 deleted at band q22. She had cardiac and CNS anomalies, dysmorphic facial features failure to thrive and developmental delay.

The molecular basis of X-linked spondyloepiphyseal dysplasia tarda.

The X-linked form of spondyloepiphyseal dysplasia tarda (SEDL), a radiologically distinct skeletal dysplasia affecting the vertebrae and epiphyses, is caused by mutations in the SEDL gene. To characterize the molecular basis for SEDL, we have identified the spectrum of SEDL mutations in 30 of 36 unrelated cases of X-linked SEDL ascertained from different ethnic populations. Twenty-one different disease-associated mutations now have been identified throughout the SEDL gene.

New' manifestations of BOR syndrome.

Defined in 1975, branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder consisting of branchial arch anomalies, hearing loss, and urinary tract malformations. It is the prototype of the non-chromosomal syndromes that have branchial arch anomalies as major clinical manifestations: BOR, branchio-otic (BO), branchio-otic-facial (BOF), and Townes-Brock syndromes. Subsequently, several clinical manifestations have expanded its phenotype.

Penile neurofibromas.

Unless omitted and underreported, penile neurofibromas are rare. Between January 2, 1982 and December 31, 1997 through the USF Regional Genetics Program we evaluated 566 propositi with suspected or clinically diagnosed neurofibromatosis (NF1, NF2, segmental NF=NF5, NF/Noonan syndrome, familial café-au-lait macules, and solitary neurofibroma, NF). These index cases were part of 32,715 families evaluated during the period.

Diabetic embryopathy.

The teratogenicity of human pregestational maternal diabetes mellitus (DM), classes B-T, is beyond any doubt and leads to a spectrum of malformations known as diabetic embryopathy (DE). Gestational DM (classes A1 and A2) is not an established teratogen yet. This is linked to its late diagnosis, usually only after the 20th week, and to the incomplete understanding of the pathogenesis of DE.

Gestational diabetes mellitus (class A): a human teratogen?

Between January 1, 1982 and December 31, 1992 we evaluated 200 children of mothers with pregestational or gestational diabetes mellitus through the University of South Florida Genetics/Dysmorphology Clinics. They were a portion of the 22,100 families seen during that period. Pregnant women with diabetes mellitus were not part of this study.

Analysis of CpG C-to-T mutations in neurofibromatosis type 1. Mutations in brief no. 129. Online.

Neurofibromatosis type 1 (NF1) is a dominant disorder caused by mutations in the NF1 gene; approximately 100 NF1 gene mutations have been published. The CpG C-to-T transition is a frequent mutation mechanism in genetic disorders. To estimate its frequency in NF1, we employed a PCR-restriction digestion method to examine 17 CpGs in 65 patients, and also screened for a CpG nonsense transition (R1947X) that occurs in 1-2% of patients.

Lenz syndrome in two sisters: clinicopathologic correlations of the ocular anomalies.

Background: The Lenz syndrome (Mendelian inheritance in Man catalog number 309,800) is a presumed X-linked recessive disorder. Major diagnostic criteria include ocular, skeletal, and urogenital manifestations. We describe two sisters and the two sons of one of them with Lenz syndrome.

Expanded phenotype of cranioectodermal dysplasia (Sensenbrenner syndrome).

Cranioectodermal dysplasia (CED) is an autosomal recessive condition characterized by defects of ectoderm-derived structures and characteristic bone anomalies. We report on a 27-month-old Caucasian girl with CED, pre- and postnatal growth retardation, microcephaly, hypoplasia of the posterior corpus callosum, photophobia, and aberrant calcium homeostasis. Since new traits were encountered, we reviewed all reported patients and one unpublished case and compared the frequency rates of the individual manifestations.

Paternal exposures and the question of birth defects.

Compared to maternal exposures, little attention has been paid to the possibility of paternally induced adverse effects on fetal development. There is increasing concern, however, about the potential for male-mediated developmental toxicity brought about by exposure to teratogenic agents. This is evidenced by the number of calls regarding paternal exposures that are received by teratogen information services.

Bronchopulmonary-foregut malformations: a continuum of paracrine hamartomas?

The bronchopulmonary-foregut malformations (BPFM) are usually sporadic, solitary cystic hamartomas involving conducting airways, arteries, venous drainage, and lung parenchyma. Transitional, compound hamartomas exist, and only their morphology is well-known. Between 1984-1994 we encountered and studied 10 unrelated patients and a stillborn infant with BPFM (out of 24,000 families).

NF1 mutation analysis using a combined heteroduplex/SSCP approach.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized predominantly by neurofibromas, café-au-lait spots, and Lisch nodules. The disease is caused by disruptive mutations of the large NF1 gene, with half of cases caused by new mutation. Less than 100 constitutional mutations have thus far been published, ranging from very large deletions to point mutations.

RET mutation screening in familial cutaneous lichen amyloidosis and in skin amyloidosis associated with multiple endocrine neoplasia.

In several families, multiple endocrine neoplasia type 2A (MEN 2A) has been found in association with cutaneous lichen amyloidosis. It has been debated, however, whether the skin amyloidosis found in MEN 2A families, localized exclusively in the interscapular area, represents the same anomaly as that found in autosomal dominant familial cutaneous lichen amyloidosis, which is more generalized. We screened two MEN 2A families with associated skin amyloidosis for germline mutations in the RET gene responsible for the MEN 2A cancer syndrome, and found the same mutation characteristic of MEN 2A in both families.

Monosomy 6q1: syndrome delineation.

We report on a girl with a de novo 6q1 interstitial deletion. To our knowledge, this is the second reported case with a deletion of 6q11-q15. We review the phenotype of monosomy 6q1.

Uniparental isodisomy of chromosome 14 in two cases: an abnormal child and a normal adult.

Uniparental disomy (UPD) of a number of different chromosomes has been found in associated with abnormal phenotypes. A growing body of evidence for an imprinting effect involving chromosome 14 has been accumulating. We report on a case of paternal UPD of chromosome 14 studied in late gestation due to polyhydramnios and a ventral wall hernia.

Fragile X syndrome: discordant levels of CGG repeat mosaicism in two brothers.

Fragile X syndrome is associated with an unstable repeated CGG trinucleotide sequence in the 5' untranslated region of the FMR-1 gene. A significant number of individuals with a mild or atypical presentation are mosaics for the CGG expansion. We report a family with two brothers.

Tracheoesophageal anomalies in oculoauriculovertebral (Goldenhar) spectrum.

Tracheoesophageal fistula, with or without esophageal atresia (TEF/EA) appears to be a defect of blastogenesis, as is the oculoauriculovertebral (Goldenhar) spectrum (OAVS), with which it has occasionally been associated. We reviewed the records of all OAVS patients evaluated through the University of South Florida Regional Genetics Program between 1985 and 1993. Of 60 OAVS patients, three had TEF/EA.

XXY male with X-linked dominant chondrodysplasia punctata (Happle syndrome).

Happle syndrome is an X-linked dominant disorder with presumed lethality in hemizygous males; familial occurrence is rare. We describe a family with Happle syndrome affecting individuals in 3 generations. A man in this family is the first known male patient with Happle syndrome.