Hypothalamic hamartoma in oral‐facial‐digital syndrome type VI (Váradi syndrome)

Stephan, Mark J.; Brooks, Kenneth L.; Moore, Douglas R.; Coll, Edward J.; Goho, C

doi:10.1002/ajmg.1320510209

Cited by 34 publications

(25 citation statements)

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“…In the present case, the gross and microscopic abnormalities in the central nervous system primarily involved the cerebellum. Absence of the vermis is a component of Dandy-Walker malformation [Friede, 1989], which has been noted in some cases of OFDS VI [Stephan et al, 1994], including the older brother of this patient. However, in addition to aplasia of the vermis, there was an apparent partial loss or failure of development of cerebellar cortical neurons, particularly granule cells, as evidenced by the near total absence of the subpial granular cell layer in medial and lateral portions of the cerebellum.…”

Section: Discussionmentioning

confidence: 89%

“…A biopsy of the mass showed ''hypercellular neuronal cells consistent with a hypothalamic hamartoma.'' Subsequent reports have described a range of posterior fossa abnormalities in OFDS VI, including occipital meningocele and posterior fossa subarachnoid cysts [Toriello, 1993], as well as Dandy-Walker anomaly [Stephan et al, 1994].…”

Section: Discussionmentioning

confidence: 98%

“…Magnetic resonance imaging in 3 additional patients described by Mü nke et al [1990] confirmed cerebellar anomalies, specifically hypoplasia/aplasia of the vermis, as a defining characteristic of OFDS VI. The spectrum of central nervous system changes in OFDS VI may include hypothalamic hamartomas in occasional cases [Mü nke et al, 1990;Stephan et al, 1994]. Stephan et al [1994] described a 2.5 × 2.2 cm suprasellar mass arising from the hypothalamic region and compressing the optic chiasm in an 8-month-old boy with bilateral central polydactyly of the hands, postaxial polysyndactyly of the right foot, and precocious puberty.…”

Section: Discussionmentioning

confidence: 99%

“…The spectrum of central nervous system changes in OFDS VI may include hypothalamic hamartomas in occasional cases [Mü nke et al, 1990;Stephan et al, 1994]. Stephan et al [1994] described a 2.5 × 2.2 cm suprasellar mass arising from the hypothalamic region and compressing the optic chiasm in an 8-month-old boy with bilateral central polydactyly of the hands, postaxial polysyndactyly of the right foot, and precocious puberty. A biopsy of the mass showed ''hypercellular neuronal cells consistent with a hypothalamic hamartoma.''…”

Section: Discussionmentioning

confidence: 99%

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Neuropathologic findings in a case of OFDS type VI (V�radi syndrome)

et al. 1998

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Oral-facial-digital syndrome type VI (OFDS VI) or Váradi syndrome is a rare autosomal-recessive disorder distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. Histopathologic characterization of the cerebellar abnormalities has not been described previously. We describe the neuropathologic findings in a stillborn, 21-week estimated gestational age (EGA) male fetus diagnosed antenatally with signs of OFDS VI. Autopsy findings included: facial abnormalities, postaxial central polydactyly of the right hand, bilateral bifid toes, and absence of cerebellar vermis with hypoplasia of the hemispheric cortex. Microscopic analysis of the cerebellum demonstrated absence of the subpial granular cell layer and disruption or dysgenesis of the glial architecture. These histopathologic findings suggest that a primary neuronal or glial cell defect, rather than an associated Dandy-Walker malformation, may account for the cerebellar abnormalities in this form of oral-facial-digital syndrome.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Neuropathologic findings in a case of OFDS type VI (V�radi syndrome)

et al. 1998

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“…HH is not patho- gnomonic but characteristic for OFD VI. 5,16,17 The association of MTS, HH, and pronounced neuroimaging findings suggests the diagnosis of OFD VI. This represents the only pattern suggesting the classification of patients with JSRD based on neuroimaging that has clinical and prognostic significance.…”

Section: Intrafamilial Comparisonmentioning

confidence: 99%

Joubert Syndrome and Related Disorders: Spectrum of Neuroimaging Findings in 75 Patients

Poretti¹,

Huisman

Scheer³

et al. 2011

AJNR Am J Neuroradiol

141

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SUMMARY: VH and MTS are the neuroimaging hallmarks of JSRD. We aimed to look at the full spectrum of neuroimaging findings in JSRD and reviewed the MR imaging of 75 patients with JSRD, including 13 siblings and 4 patients with OFD VI. All patients had VH and enlargement of the fourth ventricle. The degree of VH and the form of the MTS were variable. In most patients, the cerebellar hemispheres were normal and the PF was enlarged. Brain stem morphology was abnormal in 30% of the patients. Supratentorial findings included hippocampal malrotation, callosal dysgenesis, migration disorders, cephaloceles, and ventriculomegaly. All patients with OFD VI had a similar pattern, including HH in 2 patients. No neuroimaging-genotype correlation could be found. The wide neuroimaging spectrum in our patients supports the heterogeneity of JSRD. Neuroimaging differences in siblings represent intrafamilial heterogeneity. Due to the absence of a correlation with genotype, neuroimaging findings are of limited value in classifying patients with JSRD.ABBREVIATIONS: CC ϭ corpus callosum; HH ϭ hypothalamic hamartoma; IF ϭ interpeduncular fossa; JS ϭ Joubert syndrome; JSRD ϭ Joubert syndrome and related disorders; MTS ϭ molar tooth sign; OFD VI ϭ oral-facial-digital syndrome type VI; PF ϭ posterior fossa; PMG ϭ polymicrogyria; SCP ϭ superior cerebellar peduncles; VH ϭ vermian hypoplasia J S is a rare syndrome characterized by hypotonia, ataxia, oculomotor apraxia, facial dysmorphism, and irregular neonatal breathing.1-3 Cognitive functions are impaired in almost all patients. Based on the additional involvement of kidneys, liver, and/or eyes, 6 phenotypes of the JSRD spectrum have been defined. 1,3 One phenotype corresponds to OFD VI syndrome. In OFD VI, tongue hamartomas and/or oral frenula and/or cleft palate, mesaxial polydactyly, and HH are associated features.3 To date, mutations in 10 genes have been associated with JSRD.3 Mutations in these genes account for less than 50% of the patients.3 The same gene can cause different phenotypes (allelic heterogeneity), and different genes can be associated with the same phenotype (locus heterogeneity). 2The neuroimaging hallmarks of JSRD include VH and the MTS. MTS results from a midbrain-hindbrain malformation characterized by thickened and elongated SCP and an abnormally deep IF.4,5 Although MTS and VH have been well described, few studies demonstrated their anatomic variability and additional infratentorial and supratentorial neuroimaging findings in JSRD. 4,6,7 The aim of this study was to extend and better characterize the spectrum of neuroimaging findings in the largest series of patients with JSRD reported so far, to our knowledge. Materials and MethodsNeuroimaging data were collected by the senior author from the following sources: 1) his personal cohort of patients with JSRD diagnosed during a period of Ͼ30 years, 2) patients referred for a second opinion, and 3) requests to evaluate clinical and neuroimaging data of patients with a definite or probable diagnosis of JSRD. The inclu...

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Autosomal dominant inheritance of hypothalamic hamartoma associated with polysyndactyly: Heterogeneity or variable expressivity?

Grebe

Clericuzio

1996

Am. J. Med. Genet.

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We report on a two-generation family exhibiting dominant inheritance of complex polysyndactyly associated with hypothalamic hamartoma. These individuals have some manifestations of Pallister-Hall syndrome (PHS), but their phenotype is milder. The proposita is a 16-year-old girl with polysyndactyly of the hands and feet, short stature, and a large hypothalamic hamartoma. Her brother and father also have polysyndactyly and a hypothalamic mass on MRI scan. All three have normal appearance and intelligence, with normal pituitary function. Several other paternal relatives have polysyndactyly as well. We propose that this family may represent a clinically and perhaps genetically distinct entity from PHS, based on normal survival, normal intelligence, lack of endocrine dysfunction or facial anomalies, and few other structural malformations. Linkage analysis is in progress to determine whether this represents a benign form of PHS or a genetically separate condition. The phenotypic differences between these cases and classic PHS have important prognostic and recurrence risk implications.

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Hypothalamic hamartoma in oral‐facial‐digital syndrome type VI (Váradi syndrome)

Cited by 34 publications

References 28 publications

Neuropathologic findings in a case of OFDS type VI (V�radi syndrome)

Neuropathologic findings in a case of OFDS type VI (V�radi syndrome)

Joubert Syndrome and Related Disorders: Spectrum of Neuroimaging Findings in 75 Patients

Autosomal dominant inheritance of hypothalamic hamartoma associated with polysyndactyly: Heterogeneity or variable expressivity?

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