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J H Hersh

Publications and source records attributed to J H Hersh.

At least 19 recordsLinked to original sources
PubMed2001

Fetal valproate syndrome and autism: additional evidence of an association.

Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.

Autistic Disorder↗
PubMed2000

Case of partial duplication 2q3 with characteristic phenotype: rare occurrence of an unbalanced offspring resulting from a parental pericentric inversion.

We report on a male infant with partial trisomy 2q (q34-->qter) resulting from a maternal pericentric inversion of chromosome 2 (p25. 2q34). The infant had clinical findings similar to the characteristic phenotype associated with a partial duplication of chromosome 2q3. Carriers of pericentric inversions of chromosome 2 have an increased risk of pregnancy loss but have only rarely been reported to have a liveborn offspring with an unbalanced chromosome constitution. This case further confirms the risks associated with a pericentric inversion of chromosome 2 and is the second report with manifestations of the trisomy 2q3 phenotype.

Adult↗
PubMed2000

Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review.

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

Abnormalities, Multiple↗
PubMed1998

Changing phenotype in Floating-Harbor syndrome.

We report on a girl with Floating-Harbor syndrome, trigonocephaly due to metopic suture synostosis, preauricular pit, hypoplastic thumb, subluxated radial head, and Sprengel deformity. A review suggests that trigonocephaly may be an important craniofacial manifestation in this syndrome that is recognizable in infancy. With time, this finding appears to become less noticeable, and the face develops a triangular shape, accentuated by a broad and bulbous nose.

Abnormalities, Multiple↗
PubMed1998

The surgical management of the upper extremity anomalies associated with Du Pan syndrome.

Du Pan syndrome is a rare condition comprising complex brachydactyly with fibular hypoplasia that is inherited in an autosomal recessive manner. This article describes experience gained through the management of four patients with this disorder. The surgical management of the upper limb abnormalities is discussed and a detailed timetable for their treatment is suggested.

Abnormalities, Multiple↗
PubMed1998

Predictive value of fetal ultrasonography in the diagnosis of a lethal skeletal dysplasia.

BACKGROUND: Certain ultrasonographic findings identified in a fetus suspected of having a skeletal dysplasia may be predictive of a lethal outcome. METHODS: We evaluated 27 fetuses suspected of having a skeletal dysplasia using targeted ultrasonography between 16 and 31 weeks' gestation. Clinical examination and skeletal radiography were done after delivery. RESULTS: A skeletal dysplasia was confirmed and a diagnosis established in all but one case. The skeletal dysplasia was lethal in 23 cases and, in each case, the outcome was accurately predicted prenatally; however, three of the infants survived several months. In 11 of the 23 cases (48%), the specific diagnosis was correctly determined before birth. Ultrasonographic findings not considered to reflect a lethal outcome, were accurately predicted in two other cases. In an additional two, sonographic examination suggested a lethal osteochondrodysplasia, though both survived. Findings consistent with a lethal skeletal dysplasia included a femur length < 1st centile, combined with either a bell-shaped thorax, decreased bone echogenicity, or both. Using these criteria provided a positive-predictive value for neonatal deaths of 80% (20/25), and 92% (23/25) if the three that died in infancy were included. CONCLUSIONS: In the fetus suspected of having a skeletal dysplasia, certain findings on targeted ultrasonography frequently are predictive of a lethal outcome; the ability to predict this appears greatest when more than one of these abnormalities is present.

Bone and Bones↗
PubMed1998

Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.

We report on a case of cloverleaf skull deformity in a patient with hypochondroplasia, a disorder which has not been previously associated with this anomaly. Hypochondroplasia is a bone dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverleaf skull is a trilobar skull deformity which is etiologically and genetically heterogeneous and occurs in association with a number of disorders which result from mutations in the fibroblast growth factor receptor genes. Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C-to-A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. The occurrence of a cloverleaf skull deformity appears to represent an example of variable expressivity in hypochondroplasia and suggests that additional factors other than a specific mutation can modify the phenotype in this disorder. In addition, identification of another FGFR mutation associated with cloverleaf skull further illustrates the genetic heterogeneity of this anomaly.

Acrocephalosyndactylia↗
PubMed1997

Expansion of the phenotype in Hennekam syndrome: a case with new manifestations.

We report on a female with lymphedema, facial anomalies, intestinal lymphangiectasia, and moderate mental retardation consistent with the diagnosis of Hennekam syndrome. In addition, she had a number of other anomalies not previously described in this autosomal recessive disorder, including a congenital heart defect, atretic ear canals, vesicoureteral reflux, and rectal prolapse.

Abnormalities, Multiple↗
PubMed1997

Anophthalmia, intracerebral cysts, and cleft lip/palate: expansion of the phenotype in oculocerebrocutaneous syndrome?

We report on a patient with multiple congenital anomalies including anophthalmia, cleft lip and palate, and central nervous system anomalies similar to the case reported by Leichtman et al. [1994: Am J Med Genet 50:39-41] and to oculocerebrocutaneous (Delleman) syndrome. Although the two cases and those with oculocerebrocutaneous syndrome may represent separate but overlapping entities, our patient and the case described by Leichtman et al. [1994: Am J Med Genet 50:39-41] may represent a more severe form of oculocerebrocutaneous syndrome.

Abnormalities, Multiple↗
PubMed1997

XY gonadal dysgenesis associated with a multiple pterygium syndrome phenotype.

Most phenotypic females with an XY male karyotype do not have significant extragenital anomalies; however, some patients with additional abnormalities have been described. We report on an individual with XY gonadal dysgenesis, mental retardation, microcephaly, growth retardation, and multiple pterygia. Although not previously reported, the possible relationship between these findings is discussed in the context of evident heterogeneity of XY gonadal dysgenesis.

Child↗
PubMed1997

Greig cephalopolysyndactyly syndrome: altered phenotype of a microdeletion syndrome due to the presence of a cytogenetic abnormality.

A male had several features of Greig cephalopolysyndactyly syndrome (GCPS) and significant developmental delay. He was found to have a de novo chromosomal deletion of chromosome no. 7 involving p13; this resulted in loss of the zinc finger gene, GLI3, which is the candidate gene in this syndrome. Modification of the CGPS phenotype in a sporadic case emphasizes the importance of searching for a chromosomal origin of this autosomal dominant disorder. Detection of a chromosomal deletion in these patients may be associated with a poor prognosis from the standpoint of cognitive development, and the potential for other structural abnormalities not normally associated with GCPS.

Abnormalities, Multiple↗
PubMed1997

A male with fetal valproate syndrome and autism.

Fetal valproate syndrome (FVS) is characterized by minor craniofacial anomalies, major organ malformations, and developmental delay. We report on a patient who has a clinical phenotype compatible with both FVS and autism. The presence of an autistic disorder in a previously reported case of FVS and similar findings in our patient suggest that a relation between this known teratogen and autism may exist.

Anticonvulsants↗
PubMed1996

A clinical and molecular study of mosaicism for trisomy 17.

Trisomy 17 has never been reported in a live birth. We present a case of mosaic trisomy 17 in a male presenting with mental retardation, seizures, attention deficit hyperactivity and autistic disorders, hearing loss, growth retardation, microcephaly, and minor anomalies. Although peripheral blood lymphocyte chromosomes were normal, trisomy 17 was present in the skin fibroblasts. The percentage of abnormal cells appears to have increased from 18% in an initial skin biopsy at age 3 years 8 months to 80% at age 8 years 8 months. Molecular analysis using 13 highly polymorphic markers spanning the length of chromosome 17 demonstrated the extra chromosome 17 in the skin to be of paternal origin. Three alleles were never seen in the trisomic cell line, suggesting that the extra chromosome arose through a mitotic duplication error after conception. Uniparental disomy was excluded in the euploid blood sample. Although Smith-Magenis syndrome involves a deletion of proximal 17p, some of the clinical features of this mosaic trisomy 17 patient, such as decreased REM sleep and increased tolerance to pain, are suggestive of phenotypic features observed in Smith-Magenis syndrome. We speculate that there are dosage-sensitive genes located in 17p11.2 that produce these phenotypes for either deficiencies or over-expression of their gene products.

Abnormalities, Multiple↗
PubMed1995

Mirror image duplication of the hands and feet: report of a sporadic case with multiple congenital anomalies.

Mirror image duplication of the hands and feet is a rare entity. Based on 3 previous reports, findings include nasal abnormalities, dimelia of ulna and fibula, tibial hypoplasia and mirror image duplication of hands and feet. We report on a sporadic case in which mirror image duplication was associated with multiple congenital anomalies. Although these cases may represent variable expression of the same dominantly transmitted complex polysyndactyly syndrome, it is possible that mirror image duplication of the hands and feet is a manifestation common to a number of distinct clinical entities. During limb bud development, duplication and aberrant positioning of the zone of polarizing activity in relation to the apical ectodermal ridge may account for the anatomic abnormalities of the hands and feet in these patients.

Abnormalities, Multiple↗
PubMed1995

The impact of major congenital malformations on mortality in a neonatal intensive care unit.

Neonatal mortality due to congenital malformations or genetic disorders has not decreased despite a decrease in overall neonatal deaths with recent advances in medical technology. As a consequence, an increasing percentage of neonatal deaths is attributable to congenital malformations and genetic disorders. This study retrospectively reviewed neonatal deaths associated with congenital malformations over an 11-year period in the neonatal intensive care unit (NICU) at Kosair Children's Hospital, Louisville, Kentucky. Presently, congenital malformations are responsible for approximately 45% (range 32% to 61%) of deaths in the NICU with congenital heart disease, lethal genetic disorders, and pulmonary hypoplasia being the main contributors. Other major causes of neonatal death included extreme prematurity, respiratory disorders, necrotizing enterocolitis, sepsis, asphyxia, and primary pulmonary hypertension. It is important that clinicians are aware that improved survival is expected for most diseases because of technological advances, but that further significant reductions in neonatal mortality will depend on genetic counseling and prevention of congenital malformations.

Congenital Abnormalities↗
PubMed1995

A non-trophoblastic tumor co-existing with a triploid fetus.

Non-trophoblastic neoplasms are the most frequent, benign tumors of the placenta, occurring in approximately 1% of all placentas examined. A case is described of a 24-year-old woman who presented with severe, early-onset pre-eclampsia, high human chorionic gonadotropin (hCG) levels, and a triploid fetus and who was found to have a small choriohemangioma. The woman, gravida 2 para 1, was referred to our hospital for perinatal evaluation. The fetus, gestational age 18 weeks 3 days, had fetal growth restriction with multiple congenital anomalies. The fetal karyotype was 69,XXY. Compared with the normal range for this gestational age, the beta-hCG level was significantly elevated (1,054,000 mIU/ml) as was the maternal serum alpha-feto-protein measurement (539.1 ng/ml). Sonographically, the placenta appeared hydropic, irregularly shaped, and gelatinous. A suction dilatation and evacuation under sonographic guidance was performed. Histological examination of placental tissue revealed hydropic degeneration of the chorionic villi. The specific histological features of a partial molar pregnancy were not present. However, there were changes consistent with a choriohemangioma. Flow cytometric DNA analysis performed on formalin-fixed, paraffin-embedded tissue blocks of placenta showed triploidy. Immunohistochemical staining with human placental alkaline phosphatase was consistent with a hydropic degeneration pattern. We conclude, first, that triploidy does not always imply the presence of a partial mole. Second, the dictum, that pre-eclampsia, if it occurs under 20 weeks' gestation, must be associated with a molar pregnancy, may not hold when placental aneuploidy is present. Although the findings in this pregnancy could have been incidental, there may be an association between a choriohemangioma and polyploidy.

Abortion, Induced↗