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Biomedical subjects

B G Kousseff

Publications and source records attributed to B G Kousseff.

At least 37 records · Page 2Linked to original sources
PubMed1995

Peripheral neuropathy in Ehlers-Danlos syndrome.

Two unrelated male patients with clinical manifestations of Ehlers-Danlos syndrome type III and peripheral neuropathy are presented. At age 13 years, one developed bilateral brachial plexus palsy unrelated to trauma and 2 years later, a right lumbosacral plexopathy. The other presented at age 3 years with a left brachial plexopathy after sustaining a fracture of the lateral condyle of the right humerus. In both patients, nerve conduction velocities demonstrated conduction block across the brachial plexus and recovery was incomplete, indicating that peripheral neuropathy is a serious complication of Ehlers-Danlos syndrome. Its prompt diagnosis facilitates the care of patients with this syndrome. Increased ligament laxity/stretchability and mechanical trauma may play an important role in the pathogenesis of the neuropathy.

Adolescent↗
PubMed1995

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. These results suggest that TEF/EA in association with OAVS is underreported. The occurrence of TEF/EA should prompt a thorough search for other known anomalies of OAVS.

Abnormalities, Multiple↗
PubMed1995

Multiple endocrine neoplasia 2 (MEN 2)/MEN 2A (Sipple syndrome).

Multiple endocrine neoplasia type 2A (MEN 2A, Sipple syndrome) is an autosomal dominant phakomatosis and is most likely a paracrinopathy. The cardinal manifestations of MEN 2A--medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism--indicate that the condition is one of the inherited cancer syndromes. Cutaneous, lichen amyloidosis-like lesions place MEN 2A among the genodermatoses. The gene of MEN 2A, designated as MEN2A, is in the pericentromeric region of chromosome 10; this allows for reliable prenatal and presymptomatic DNA diagnosis.

Adrenal Gland Neoplasms↗
PubMed1994

Brachmann-de Lange syndrome. 1994 update.

OBJECTIVE: To update the phenotype, cause, mode of inheritance, and certainty of the diagnosis of Brachmann-de Lange syndrome. DESIGN: Case series with comparative review of pertinent literature. SETTING: A tertiary university-based pediatric genetic clinic. PARTICIPANTS: All 37 children with Brachmann-de Lange syndrome examined between January 1982 and December 1992. INTERVENTION: None. MAIN RESULTS: The syndrome was previously undiagnosed in 33 of the patients. Thirty-one were white, four were Hispanic, and two were African-American. In 22 of 32 patients, intrauterine growth had been retarded; in 32 of 37 subjects, height was below the National Center for Health Statistics fifth percentile and growth velocity was less than the 50th percentile in those with serial measurements. Compared with reference texts and reported studies of Brachmann-de Lange syndrome, the incidences of cleft palate (eight of 37), hypospadias (six of 18), nuchal webbing (four of 37), seizures (14 of 37), and hypopituitarism (four of 13) in the studied patients were increased. Standard karyotypes were obtained in 36 patients; all were normal. Familial cases are infrequent, and intrafamilial variation makes them difficult to diagnose. Two patients were half first cousins; their parents (who were half siblings) had minor manifestations of Brachmann-de Lange syndrome, including hypertrichosis and developmental delay, suggesting possible autosomal dominant inheritance in this family. CONCLUSIONS: The dysmorphic abnormalities associated with Brachmann-de Lange syndrome may be expanded to include cleft palate, nuchal webbing, and hypospadias, while the presence of seizures and hypopituitarism extend the functional abnormalities found in these patients. Most cases are sporadic, and in the absence of laboratory biomarkers for Brachmann-de Lange syndrome, the certainty of the diagnosis is high but not 100%. Submicroscopic deletion 3q25-3qter or uniparental disomy remains as a plausible cause of the syndrome.

Adult↗
PubMed1994

Two NF1 mutations: frameshift in the GAP-related domain, and loss of two codons toward the 3' end of the gene.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders, and is due to mutations within the NF1 gene on chromosome 17q11.2. Only the middle 400 amino acids of the associated protein (neurofibromin) have a known function, comprising a GTPase-activating-protein (GAP) domain. The large gene size and the fact that approximately half of cases are due to new mutation render mutation analysis difficult. NF1 direct mutation characterization is important for development of DNA diagnostic procedures, analysis of phenotype/genotype correlations, and delineation of functions for specific domains of neurofibromin. We report two mutations detected using PCR amplification of individual exons followed by heteroduplex analysis. One is a single base deletion in exon 24 which is predicted to result in a protein truncated early in the GAP-related domain. The other is a 6-bp deletion in exon 39 which is predicted to result in loss of two amino acids in the mature protein near the carboxy-terminus. The exon 24 mutant allele was shown to be expressed by RNA PCR analysis. The exon 39 mutation suggests that those two amino acids are important in neurofibromin function, perhaps indicating a functional domain.

Adolescent↗
PubMed1993

Physical growth in Brachmann-de Lange syndrome.

Growth in 30 patients with Brachmann-de Lange syndrome (BDLS) was evaluated and found to be deficient in 27/30, with 17/27 having intrauterine growth retardation (IUGR). In 12/27 patients, endocrine evaluations have been completed. Seven of 12 were normal and 4/12, one with empty sella, had "classical" growth hormone deficiency with extreme short stature, markedly delayed skeletal maturation and subnormal growth hormone secretion in response to provocative stimuli. One of 12 patients had discordance between insulin growth factor I levels and growth hormone responses to insulin and clonidine suggestive of end organ resistance to growth hormone. It appears that the hypothalamic-pituitary function is compromised in at least some BDLS patients. Thus, endocrine evaluations are warranted for the patients with short stature.

Adolescent↗
PubMed1993

Pleiotropy in Coffin-Lowry syndrome: sensorineural hearing deficit and premature tooth loss as early manifestations.

We report on 7 patients (6 M, 1 F) with Coffin-Lowry syndrome who have a sensorineural hearing deficit in addition to developmental delay and characteristic facial changes. One of the patients also had a history of premature exfoliation of primary teeth. These are previously unappreciated clinical signs that may aid in the early diagnosis of Coffin-Lowry syndrome. Early diagnosis and recognition of a hearing deficit in the patient can lead to the use of hearing aids to help the patient achieve his or her full potential. These "new" clinical manifestations expand the phenotype of Coffin-Lowry syndrome and constitute an additional indication of pleiotropy.

Child↗
PubMed1993

Complex chromosome rearrangement with ankyloblepharon filiforme adnatum.

A Caucasian boy with a de novo complex chromosome rearrangement owing to six chromosome breaks was small for gestation with microcephaly, complex heart defect, hypotonia, left auricular pit, simian creases, and ankyloblepharon filiforme adnatum. The rearrangement included two translocation, t(15;21) (q22;q22) and t(3;11)(q21;q11), with the derivative 3 showing in addition pericentric inversion (p11q11) and interstitial deletion (q11q21). Based on parental satellite polymorphisms of chromosomes 15 and 21, the paternal gamete appeared to be the source of the chromosome rearrangement. There was no evidence of mitotic chromosome instability. A review of 36 reported patients with complex chromosome rearrangements secondary to more than four breaks indicates that complex chromosome rearrangements are compatible with gamete survival, zygote formation, and postnatal life. The latter is usually compromised by structural defects, growth retardation, and often mental retardation.

Abnormalities, Multiple↗
PubMed1992

Hypothesis: Jadassohn nevus phakomatosis: a paracrinopathy with variable phenotype.

It has been postulated that the phakomatoses are paracrine growth regulation disorders (paracrinopathies). To determine how Jadassohn nevus phakomatosis (JNP) may fit such a pathogenetic model, a phenotype analysis of 13 propositi with JNP and a review of most reported JNP patients were done. The phenotypes of the propositi and the reviewed patients showed a great variability from a solitary congenital epidermal nevus to extensive cutaneous lesions with associated severe non-cutaneous anomalies. Review of long-term observations of JNP patients demonstrated considerable phenotypic changes within and beyond the boundaries of the nevi. The changes included a multitude of postnatal rare benign and/or malignant tumors and unusual manifestations: renal rickets, hepatomegaly, visceral cysts, vasculopathy, and even gangrene. Thus, a life-long predisposition to dysregulation of paracrine growth factors (GFs, regulatory peptides, peptide regulatory factors, and cytokines), foremost somatomedin-C (Sm-C, IGF-I), epidermal, fibroblast, platelet-derived GFs, and transforming GF-beta is implied. Laboratory evidence for the presumed GF dysregulation in the phakomatoses came from tissue culture study of patients with neurofibromatosis type 1 (NF-1). Compared to controls their "normal" skin showed ultrastructural changes of markedly increased number of melanin macroglobuli within the melanocytes. Paracrine GFs as relevant to hamartomatous growth were incriminated by radioimmunoassays of cutaneous neurofibromas showing two-fold or greater increase of Sm-C levels compared to the levels in the adjacent skin. Thus, NF-1 appears to be a paracrinopathy. JNP shows many more dynamic changes throughout the life span of the patients than NF-1. In the near future paracrinology may aid endocrinology and oncology in treating patients with disorders of these three growth mechanisms in man.

Adolescent↗
PubMed1992

Ankyloblepharon filiforme adnatum.

We treated 4 infants with ankyloblepharon filiforme adnatum (AFA), an uncommon anomaly in which the apposing eyelid margins are connected by abnormal tissue strands. One infant had AFA alone, one had Hay-Wells syndrome, characterized by ectodermal dysplasia, and the other 2 had chromosome abnormalities, trisomy 18, and complex chromosome rearrangement, with visceral malformations. Despite heterogeneity and phenotypic variability, these developmental abnormalities shared (1) involvement of tissues growing in apposition and (2) temporal overlap of their occurrence. This suggests a common defect in the mechanism(s) that regulate tissue fusion at multiple sites during development.

Abnormalities, Multiple↗
PubMed1992

The genetics of malignant melanomas.

A review of the hereditary aspects of the malignant melanomas showed causal heterogeneity and similar pathogenesis based on the dysregulation of the paracrine/autocrine growth mechanisms. The genetically different malignant melanomas have a range of recurrence risks from 1% for the nonfamilial, solitary, malignant melanoma to a risk exceeding 70% for the syndromic melanomas of neurocutaneous melanosis and the nine types of xeroderma pigmentosum. A recurrence risk of 6% is relevant to the members of dysplastic nevus syndrome families without malignant melanomas and the risk increases in excess of 50% for the individuals of families with dysplastic nevi and more than one malignant melanoma.

Cytogenetics↗
PubMed1992

Cleft palate and complex chromosome rearrangements.

Two of three unrelated children with de novo congenital complex chromosome rearrangements (CCR) with more than four chromosome breaks had cleft lip and palate as one of several congenital anomalies. In patient 1, unilateral complete cleft of the primary and secondary palates accompanied severe ectrodactyly, bilateral posterior choanal atresia and several minor congenital anomalies. Karyotypes of peripheral lymphocytes and skin fibroblasts showed five derivative chromosomes with six break points. There were two translocations, t(2;5), t(3;11) and an interstitial deletion, del(13)(q12q14). Patient 2 had a bilateral complete cleft of the lip and palate, in addition to slow pre- and postnatal growth and minor congenital anomalies. Peripheral lymphocytes and palatal mucosa fibroblasts karyotypes showed five derivative chromosomes with six break points. A partial deletion of 10p, two translocations, t(2;3), t(7;18) and an inversion of the derivative chromosome 2 were present. In both patients, a "major catastrophe" of unknown etiology in one of the parental gametes appeared to be the event leading to the stable CCR without evidence of persistent chromosome instability. All four parents had normal karyotypes. The presence of palatal clefts in these patients indicates that dysmorphologists and pediatricians have to consider CCR whenever taking care of a patient with cleft palate, particularly if additional anomalies, no matter how subtle, are present. The detection and interpretation of the latter anomalies are essential for the diagnosis and management of these patients. Accurate cytogenetic diagnosis determines the short- and long-term prognosis and facilitates genetic counseling in regard to life-span, quality of life and reproductive plans of patients and parents.

Abnormalities, Multiple↗
PubMed1991

Duplication 3q(q21----qter) without limb anomalies.

We report on a 2.5-month-old boy with hypertelorism, hypertrichosis, anteverted nostrils, malformed ears, thin lips, downturned corners of the mouth, micrognathia, short neck, cryptorchidism, and bilateral simian creases without limb anomalies. Cytogenetic studies showed a duplication 3q----qter 46,XY,der(6),t(3;6)(q21;p25)pat. The absence of limb anomalies is noteworthy; all 12 previously reported patients with the same duplication had limb anomalies. The uniqueness of this report provokes speculations regarding limb morphogenesis in embryos with chromosome anomalies. The concepts of chronogenetics, heterochrony, and developmental field defects appear relevant to yet another set of patients with chromosome anomalies.

Chromosome Banding↗
PubMed1991

Sipple syndrome with lichen amyloidosis as a paracrinopathy: pleiotropy, heterogeneity, or a contiguous gene?

A five-generation white family with multiple endocrine neoplasia type 2A had six affected members. Two, a mother and her daughter, had interscapular cutaneous pruritic lesions resembling macular/lichen amyloidosis. In the daughter, light microscopy showed homogeneous aggregates in the papillary dermis. Crystal violet staining showed metachromasia and indicated that the deposits were amyloid. This is the fourth family with familial medullary thyroid carcinoma with cutaneous amyloidosis and as such it allowed comparative analysis. Genetic heterogeneity, a contiguous gene, and pleiotropy were considered. It appears that multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma with cutaneous amyloidosis represents the phenotypic variability of the expression of a pleiotropic gene. The condition is one of the predominantly ectodermal autosomal dominant phakomatoses and is most likely a paracrinopathy.

Adolescent↗
PubMed1991

Unique brain anomalies in an infant of a diabetic mother.

An offspring of a class F diabetic primigravida with marginal control during the first 8 weeks of the gestation had a level II sonogram at 23 weeks. It showed polyhydramnios and "hydrocephaly." Macrosomia, right hydroureter, megacystis and premature birth corroborated the diagnostic impression of diabetic embryopathy. At age 3 years, the child functions within the moderate range of mental retardation. Angiography, choanogram, CT and MRI scans showed unique CNS abnormalities that appeared secondary to a hamartomatous growth within the left cerebral hemisphere. Such anomaly, most likely a part of the phenotype of the diabetic embryopathy, implies a growth disturbance secondary to dysregulated paracrine growth factors (somatomedins, nerve growth factor, panregulin and/or their receptors in this case). It also indicates a possibility of interaction between two dysregulated major growth mechanisms; the endocrine in the mother considered responsible for the overall phenotype of the diabetic embryopathy/fetopathy and the paracrine fine tuning mechanism in the embryo incriminated by the hamartomatous over/undergrowth.

Adult↗