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Biomedical subjects

Antonio Richieri-Costa

Publications and source records attributed to Antonio Richieri-Costa.

At least 19 recordsLinked to original sources
PubMed2006

PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI.

We report five Brazilian probands with PATCHED (PTCH) mutations and highly variable phenotypes with holoprosencephaly in four cases and holoprosencephaly-like facial features with a normal MRI in a fifth case. Three of our mutations were novel: Ala443Gly, Val751Gly, and Val908Gly. Two patients had the same mutation (Val908Gly), but were phenotypically different: alobar holoprosencephaly, absent nasal septum, and midline cleft lip-palate in one case, and lobar holoprosencephaly, macrocephaly, hypertelorism, clefting of the nose, severe microphthalmia, and a single maxillary central incisor in the other. One of our patients had a Thr1052Met mutation, holoprosencephaly-like facial features, and a normal MRI. Ming et al. [(2002); Hum Genet 110:297-301] reported an identical mutation, but with alobar holoprosencephaly.

Abnormalities, Multiple↗
PubMed2006

GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum?

We report four patients with GLI2 mutations together with their associated phenotypes: (1) holoprosencephaly-like phenotype, (2) anophthalmia, branchial arch anomalies, and CNS abnormalities, (3) heminasal aplasia and orbital anomalies, and (4) lobar holoprosencephaly. This diversity of phenotypes expands our understanding. Findings include not only (1) holoprosencephaly or a holoprosencephaly-like phenotype, but also (2) heminasal aplasia with orbital anomalies, and (3) branchial arch anomalies of the type seen in hemifacial microsomia with anophthalmia and in oculoauriculofrontonasal syndrome. Finally, this is the first report of a double mutation involving GLI2 and PTCH in the same patient.

Abnormalities, Multiple↗
PubMed2006

SIX3 mutations with holoprosencephaly.

Here, we report six Brazilian patients with holoprosencephaly caused by SIX3 mutations. Missense mutations were more common than frameshift mutations. Comparison of patients with missense versus frameshift mutations was essentially unremarkable. Our cases suggest that SIX3 mutations result in a more severe phenotype than other gene mutations for holoprosencephaly. One patient had a double SIX3 mutation, which has not been reported previously. In our SIX3 mutations, three were transmitted by the paternal side, two were transmitted by the maternal side, and one was a de novo event. Mutations in normal parents with severe involvement of their offspring does not allow prediction of phenotypic severity, which makes genetic counseling difficult.

Brain↗
PubMed2006

Holoprosencephaly: clinical evaluation on audiological and brainstem electrophysiological profiles.

This study evaluated audiological and electrophysiological profiles in 13 patients with holoprosencephaly. All patients had imaging evaluation by magnetic resonance imaging and molecular screening for the genes SHH, GLI2, and SIX3. Each patient underwent clinical (otological and vestibular antecedents, otoscopy) and instrumental (tympanometry, auditory brainstem response--ABR) evaluation to compare hearing and the electrophysiological profile possibly occurring in patients with these mutations. To our knowledge there are no systematic studies correlating molecular/imaging and evoked potentials in patients with HPE. Here, we discuss the audiological and electrophysiological profiles of patients and the possible role of the genes studied on the overall findings.

Acoustic Impedance Tests↗
PubMed2006

Language skills and neuropsychological performance in patients with SHH mutations and a holoprosencephaly-like phenotype.

Here, we evaluate linguistic skills and neuropsychological performance in a sample of patients with SHH mutations and a holoprosencephaly (HPE)-like phenotype, a minor form of classic HPE. Our findings suggest that patients with SHH mutations and a HPE-like phenotype have normal cognitive ratios and significant language impairment. Imaging evaluation by magnetic resonance imaging (MRI) was normal in three patients and in one there was hypoplasia of the anterior commissure and the presence of a temporal cyst, apparently not related to the clinical findings.

Adolescent↗
PubMed2006

Macrostomia, preauricular tags, and external ophthalmoplegia: a new autosomal dominant syndrome within the oculoauriculovertebral spectrum?

OBJECTIVE: First and second branchial arch involvement during early embryonic development results in a wide spectrum of anomalies that encompass diverse, superimposed, and heterogeneous phenotypes within the so-called oculoauriculovertebral spectrum. Nine members of a Brazilian family presenting typical branchial arch involvement in association with external opthalmoplegia are reported. CONCLUSION: Macrostomia or abnormal mouth contour, preauricular tags, and uni- or bilateral ptosis were present in association in several patients. To our knowledge, this is the first report on this type of autosomal dominant condition. Clinical and genetic aspects are discussed.

Blepharoptosis↗
PubMed2005

Periventricular neuronal heterotopia, oro-facio-digital anomalies, and microphthalmia. A new syndrome?

Congenital malformations involving the face, oral cavity, and digits are the main findings in the oro-facio-digital (OFD) syndromes. Various eye anomalies and central nervous system involvement have also been reported in this condition. Here we report on a Brazilian boy with features belonging to the clinical spectrum of the OFD syndromes. He also had additional findings of periventricular nodular heterotopia (PVNH), asymmetric limb involvement, and microphthalmia. This unusual pattern of anomalies has not been reported previously and appears to be unique.

Abnormalities, Multiple↗
PubMed2004

Newly recognized syndrome with heminasal aplasia and ocular anomalies or wider spectrum of heminasal aplasia/atypical clefting syndrome?

We report on five unrelated Brazilian patients with heminasal aplasia associated with diverses anomalies, including lateral proboscis, and anomalies of the eye and first branchial arch. We suggest that these patients represent different conditions within the spectrum of the heminasal aplasia malformation. Clinical, genetic, and differential diagnosis are discussed.

Abnormalities, Multiple↗
PubMed2004

The Syndrome of Frontonasal Dysplasia, Callosal Agenesis, Basal Encephalocele, and Eye Anomalies - Phenotypic and Aetiological Considerations.

We report ten sporadic cases of Brazilian patients with facial midline defects, callosal agenesis, basal encephalocele, and ocular anomalies. This very rare cluster of anomalies has been well reported before. However, only until recently it is recognized as a syndrome belonging to frontonasal dysplasia spectrum. The ten cases confirm a distinct clinical entity and help to define the phenotype more precisely than previously. Up to now etiology remains unknown, although we conjecture that it is due to a mutation in TGIF gene.

Journal Article↗
PubMed2004

Clinical genetic study of 144 patients with nonsyndromic hearing loss.

Hearing loss constitutes an important category of congenital defects that can be isolated or part of the phenotypic spectrum of several syndromes. A clinical genetic study was performed on a sample of 144 patients with nonsyndromic hearing loss, establishing the sex distribution, type, degree, symmetry, laterality, progression, etiology, and, when possible, inheritance pattern.

Adolescent↗
PubMed2004

Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate in Brazilian patients: results of a large case-control study.

OBJECTIVE: Transforming growth factor-alpha (TGFA) was the first gene suggested to be associated with nonsyndromic cleft lip, cleft palate, or both (CL/ P). There are, however, still controversies of the effect of TGFA on the predisposition of this malformation. To contribute to a better understanding of the role of this gene in the occurrence of CL/P we undertook a case-control study including patients and controls ascertained in different regions of the country. DESIGN: We examined the C2/TaqI variant of the TGFA gene in 536 patients with nonsyndromic CL/P and 412 controls. The TGFA genotype frequencies in patients were compared with controls using chi-square or Fisher exact test. DNA, obtained from peripheral blood or buccal swabs, was genotyped for the TaqI polymorphism of TGFA. SETTING: The probands and corresponding controls were ascertained in different centers of Brazil, partly representing the ethnic admixture of our population. RESULTS: The TGFA genotype distribution was very similar in patients with CL/P ascertained in the three different regions of Brazil. However, a discrete difference was observed between controls of Säo Paulo and Ceará (chi-square = 3.605; p = 0.058), with a lower value of the C2/Taq allele frequency in controls of CE (0.04). These data reinforce that this polymorphic system is heterogenous among different ethnic groups. In addition, no evidence was found for an association of TGFA with CL/P in this case-control study. CONCLUSION: These data further suggest that TGFA is not a relevant modifier locus for the occurrence of CL/P.

Adolescent↗
PubMed2003

Waardenburg syndrome: clinical differentiation between types I and II.

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS.

Brazil↗