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N H Robin

Publications and source records attributed to N H Robin.

At least 55 records · Page 3Linked to original sources
PubMed1997

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis.

Adult↗
PubMed1996

Syntelencephaly in an infant of a diabetic mother.

Here we report on an infant of a diabetic mother (IDM) with midline interhemispheric "fusion" (MIF), or syntelencephaly. This is a rare anomaly characterized by segmental failure of cleavage of the cerebral hemispheres and other brain structures in the posterior frontal and parietal regions, with a normal interhemispheric fissure anterior and posterior to the "fused" region. While there is obvious overlap with holoprosencephaly (HPE), this condition differs from HPE in that the midline "fusion" in MIF is complete but segmental, while the structural brain anomalies seen in the HPE spectrum progress smoothly in severity in a posterior to anterior "fusion." However, while it is apparent that there are key distinctions between MIF and HPE, in all likelihood they arise from a similar pathogenetic mechanisms. We therefore suggest that MIF is a distinct variant of the HPE spectrum of midline brain anomalies. Given the known increased incidence of HPE in IDMs, MIF is likely a maternal diabetes-associated malformation.

Adult↗
PubMed1996

The good that we do.

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Cleidocranial Dysplasia↗
PubMed1996

Craniosynostosis, Philadelphia type: a new autosomal dominant syndrome with sagittal craniosynostosis and syndactyly of the fingers and toes.

The acrocephalosyndactyly syndromes (ACS) are a group of clinically similar disorders that share the manifestations of craniosynostosis and a variety of hand and foot anomalies. Here we report on a 5-generation kindred segregating sagittal craniosynostosis and syndactyly of the fingers and the toes in an autosomal dominant manner. The anomalies seen in this kindred comprise a syndrome distinct from other craniosynostosis syndromes. For this novel syndrome, we propose the name craniosynostosis, Philadelphia type.

Acrocephalosyndactylia↗
PubMed1996

Frontonasal malformation and cloacal exstrophy: a previously unreported association.

We report on a child with frontonasal malformation (FNM) and cloacal exstrophy, a combination of findings that have not been reported previously. In FNM and cloacal exstrophy, associated malformations are rare. FNM and cloacal exstrophy both represent abnormalities of the development of the midline field; this combination of anomalies in this patient suggests an impairment of caudal and cranial midline development during blastogenesis.

Abnormalities, Multiple↗
PubMed1995

Classical Noonan syndrome is not associated with deletions of 22q11.

Deletions of 22q11 cause DiGeorge sequence (DGS), velo-cardio-facial syndrome (VCFS), conotruncal anomaly face syndrome, and some isolated conotruncal heart anomalies. Demonstration of a 22q11 deletion in a patient with manifestations of DGS and Noonan syndrome (NS) has raised the question of whether NS is another of the chromosome 22 microdeletion syndromes. This prompted us to evaluate a cohort of patients with NS for evidence of 22q11 deletions. Five of 6 NS propositi studied in our laboratory with marker N25 (D22S75) did not have a 22q11 deletion. A 2-month-old infant with several findings suggestive of NS did have a 22q11 deletion, suggesting that a small number of 22q11 deletion propositi may present with a NS-like picture. However, most cases of NS must have another cause.

Adolescent↗
PubMed1995

Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.

Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

Abnormalities, Multiple↗
PubMed1995

Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.

Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder which affects the bones of the skull, hands and feet. Previously, we have mapped PS in a subset of families to chromosome 8cen by linkage analysis and demonstrated a common mutation in the fibroblast growth factor receptor-1 (FGFR1) gene in the linked families. Here we report a second locus for PS on chromosome 10q25, and present evidence that mutations in the fibroblast growth factor receptor-2 (FGFR2) gene on 10q25 cause PS in an additional subset of familial and sporadic cases. Three different point mutations in FGFR2, which alter the same acceptor splice site of exon B, were observed in both sporadic and familial PS. In addition, a T to C transition in exon B predicting a cysteine to arginine substitution was identified in three sporadic PS individuals. Interestingly, this T to C change is identical to a mutation in FGFR2 previously reported in Crouzon syndrome, a phenotypically similar disorder but one lacking the hand and foot anomalies seen in PS. Our results highlight the genetic heterogeneity in PS and suggest that the molecular data will be an important complement to the clinical phenotype in defining craniosynostosis syndromes.

Abnormalities, Multiple↗
PubMed1995

A gene for cleidocranial dysplasia maps to the short arm of chromosome 6.

Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia characterized by mild-to-moderate short stature, clavicular aplasia or hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth, a characteristic craniofacial appearance, and a variety of other skeletal anomalies. We have performed linkage studies in five families with CCD, with 24 affected and 20 unaffected individuals, using microsatellite markers spanning two candidate regions on chromosomes 8q and 6. The strongest support for linkage was with chromosome 6p microsatellite marker D6S282 with a two-point lod score of 4.84 (theta = .03). Furthermore, the multipoint lod score was 5.70 in the interval between D6S282 and D6S291. These data show that the gene for autosomal dominant CCD is located within a 19-cM interval on the short arm of chromosome 6, between D6S282 and D6S291.

Chromosome Mapping↗
PubMed1994

Non-immune hydrops fetalis associated with impaired fetal movement: a case report and review.

Non-immune hydrops fetalis (NIHF) is due to many different causes. Fetal hypomobility has been alluded to as a possible cause. We present a preterm fetus with NIHF secondary to fetal hypomobility. Fetal movements were undetected after the 20th week of gestation. The infant was born 8 weeks later and was edematous, had pleural effusions, and no spontaneous movements. He died on day four of life. Diffuse massive central nervous system (CNS) destruction found on post-mortem examination was thought to be the origin of the hypomobility. As all other causes of NIHF were eliminated, we propose that the NIHF in this infant was due to the hypomobility. This case then gives support to the assertion that fetal hypomobility is another cause of NIHF. The cause of the CNS catastrophy remains unelucidated.

Brain↗
PubMed1994

A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.

Pfeiffer syndrome (PS) is one of the classic autosomal dominant craniosynostosis syndromes with craniofacial anomalies and characteristic broad thumbs and big toes. We have previously mapped one of the genes for PS to the centromeric region of chromosome 8 by linkage analysis. Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. A C to G transversion in exon 5, predicting a proline to arginine substitution in the putative extracellular domain, was identified in all affected members of five unrelated PS families but not in any unaffected individuals. FGFR1 therefore becomes the third fibroblast growth factor receptor to be associated with an autosomal dominant skeletal disorder.

Abnormalities, Multiple↗
PubMed1994

Linkage of Pfeiffer syndrome to chromosome 8 centromere and evidence for genetic heterogeneity.

Pfeiffer syndrome (PS) is an autosomal dominant disorder characterized by craniosynostosis, midfacial hypoplasia, and broad thumbs and great toes. We examined 129 individuals from 11 families with PS and performed linkage studies using microsatellite markers spanning the entire genome. Strongest support for linkage was with DNA markers (D8S255, GATA8G08) from chromosome 8. Obligate crossovers exclude close linkage to this region in six families, and there was significant evidence for genetic heterogeneity. A multipoint lod score of 7.15 was obtained in five families. The 11 cM interval between D8S278 and D8S285 contains one gene for PS and also spans the centromere of chromosome 8.

Acrocephalosyndactylia↗
PubMed1993

New finding of Schinzel-Giedion syndrome: a case with a malignant sacrococcygeal teratoma.

We report on a boy with Schinzel-Giedion syndrome (SGS) with a previously unreported manifestation, a malignant sacrococcygeal teratoma. This is the second case of SGS to have a malignancy, as one earlier case had a hepatoblastoma. We postulate that the occurrence of 2 uncommon embryonic tumors among these patients with a rare syndrome may mean that risk of malignancy may be a component of this syndrome.

Abnormalities, Multiple↗
PubMed1993

Human malformations similar to those in the mouse mutation disorganization (Ds).

We report two patients with malformations similar to those seen in mice with the disorganization (Ds) mutation. The first case has a body wall defect, limb malformation, and hamartoma, while the second case has a partially duplicated foot, in addition to the other anomalies. We discuss the implications that recent advances regarding the genetic analysis of the mouse Ds locus have for the search for the human homologue.

Abnormalities, Multiple↗