25 research outputs found
Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations
Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is an autosomal dominant neurodevelopmental disorder caused by loss-of-function variants in NR2F1 and characterized by visual impairment, developmental delay, and intellectual disability. Here we report 18 new cases, provide additional clinical information for 9 previously reported individuals, and review an additional 27 published cases to present a total of 54 patients. Among these are 22 individuals with point mutations or in-frame deletions in the DNA-binding domain (DBD), and 32 individuals with other types of variants including whole-gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. We corroborate previously described clinical characteristics including developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. We also confirm a vision phenotype that includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment. Additionally, we expand the vision phenotype to include alacrima and manifest latent nystagmus (fusional maldevelopment), and we broaden the behavioral phenotypic spectrum to include a love of music, an unusually good long-term memory, sleep difficulties, a high pain tolerance, and touch sensitivity. Furthermore, we provide additional evidence for genotype-phenotype correlations, specifically supporting a more severe phenotype associated with DBD variants
Ain't No Sunshine When You Are Gone!
An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks.An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks. She initially had blurry vision and photophobia OD with a central scotoma OD on HVF testing. At that time, examination revealed a right swollen optic nerve with retinal hemorrhages. She was otherwise healthy, and denied any eye pain, neurological deficits, trauma medications, tobacco, alcohol, or drug use.A fat suppressed orbital MRI scan showed evidence of optic nerve enhancement OD.MRIIntracanalicular right optic nerve specimen showed dense fibrovascular tissue with macrophage infiltrates. Intracranial portion of the right optic nerve specimen revealed large pleomorphic and hyperchromatic atypical cells infiltrating the nerve. Sectioned tissue underwent immunostaining for GFAP, Ki67, Olig 2, and IDH1. These atypical cells were strongly GFAP positive, but were negative for Olig and IDH1. The Ki67 index of the posterior margin of the tissue was 4-5%.This patient was managed aggressively with surgical resection of the pre-chiasmal tumor, and treated post-operatively with Temozolomide and stereotactic radiotherapy treatment.Attache
Ain't No Sunshine When You Are Gone!
An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks.An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks. She initially had blurry vision and photophobia OD with a central scotoma OD on HVF testing. At that time, examination revealed a right swollen optic nerve with retinal hemorrhages. She was otherwise healthy, and denied any eye pain, neurological deficits, trauma medications, tobacco, alcohol, or drug use.A fat suppressed orbital MRI scan showed evidence of optic nerve enhancement OD.MRIIntracanalicular right optic nerve specimen showed dense fibrovascular tissue with macrophage infiltrates. Intracranial portion of the right optic nerve specimen revealed large pleomorphic and hyperchromatic atypical cells infiltrating the nerve. Sectioned tissue underwent immunostaining for GFAP, Ki67, Olig 2, and IDH1. These atypical cells were strongly GFAP positive, but were negative for Olig and IDH1. The Ki67 index of the posterior margin of the tissue was 4-5%.This patient was managed aggressively with surgical resection of the pre-chiasmal tumor, and treated post-operatively with Temozolomide and stereotactic radiotherapy treatment.Attache
Timing and frequency synchronization in orthogonal frequency division multiplexing broadband wireless systems
Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2001.Includes bibliographical references (p. 87-89).by Veeral S. Shah.M.Eng
Ain't No Sunshine When You Are Gone!
An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks.An 18 year-old Latin American female presented with progressive visual loss OD over 6 weeks. She initially had blurry vision and photophobia OD with a central scotoma OD on HVF testing. At that time, examination revealed a right swollen optic nerve with retinal hemorrhages. She was otherwise healthy, and denied any eye pain, neurological deficits, trauma medications, tobacco, alcohol, or drug use.A fat suppressed orbital MRI scan showed evidence of optic nerve enhancement OD.MRIIntracanalicular right optic nerve specimen showed dense fibrovascular tissue with macrophage infiltrates. Intracranial portion of the right optic nerve specimen revealed large pleomorphic and hyperchromatic atypical cells infiltrating the nerve. Sectioned tissue underwent immunostaining for GFAP, Ki67, Olig 2, and IDH1. These atypical cells were strongly GFAP positive, but were negative for Olig and IDH1. The Ki67 index of the posterior margin of the tissue was 4-5%.This patient was managed aggressively with surgical resection of the pre-chiasmal tumor, and treated post-operatively with Temozolomide and stereotactic radiotherapy treatment
Leopard Can't Change Its Spots - Presentation PPT
An 8 year-old Caucasian female presented with bilateral conjunctivitis, photophobia, and blurred vision. Visual acuity was 20/50 OD and 20/60 OS. She had 2-3+ anterior chamber cell and flare OU, 1+ vitreous cells OU, 2+ optic disc edema OU, and macular edema OU. She was diagnosed with anterior uveitis, vitritis, and neuroretinitis. At home, she had a cat, a rabbit, and a dog. She had recent travel to Hawaii. She reported a recent transient erythematous maculopapular rash behind her ears and neck. A full work-up was negative for bartonellosis, brucellosis, leptospirosis, toxoplasmosis, Lyme disease, and tularemia. Normal studies included serum ACE, lysozyme, ANA, chest x-ray, and HLA-B27. Systemic treatment consisted of azithromycin and rifampin. Prednisolone acetate eyedrops were added with a slow taper over 4 months when ocular inflammation resolved and vision returned to 20/20 OU. A week later, she developed new fevers, headache, nausea, vomiting, seizures and altered mental status. She developed disseminated intravascular coagulopathy, and recurrence of maculopapular rash which progressed to toxic epidermal necrolysis (TEN). MRI of the brain demonstrated bilateral thalamic signal intensities. Extensive workup was again negative for bartonellosis, tularemia, rickettsioses, and rubeola. Normal studies included anti-NMDA, HSV, HHV-6, HHV-7, CMV, VZV, EBV, Mycoplasma, West Nile, Enterovirus, Typhus, HIV, NMO, MPO, PR-3, ANCA, ANA, HMPV, Adenovirus, Parainfluenza, Influenza. Parvovirus B19 CSF PCR was negative, but subsequent bloodwork had positive IgG and negative IgM, and positive serum PCR and bone marrow PCR at low levels with no pathologic evidence of acute parvovirus disease. Ferritin and soluble IL-2 were elevated, and natural killer cell count was low. A procedure was performed
Leopard Can't Change Its Spots - Video
An 8 year-old Caucasian female presented with bilateral conjunctivitis, photophobia, and blurred vision. Visual acuity was 20/50 OD and 20/60 OS. She had 2-3+ anterior chamber cell and flare OU, 1+ vitreous cells OU, 2+ optic disc edema OU, and macular edema OU. She was diagnosed with anterior uveitis, vitritis, and neuroretinitis. At home, she had a cat, a rabbit, and a dog. She had recent travel to Hawaii. She reported a recent transient erythematous maculopapular rash behind her ears and neck. A full work-up was negative for bartonellosis, brucellosis, leptospirosis, toxoplasmosis, Lyme disease, and tularemia. Normal studies included serum ACE, lysozyme, ANA, chest x-ray, and HLA-B27. Systemic treatment consisted of azithromycin and rifampin. Prednisolone acetate eyedrops were added with a slow taper over 4 months when ocular inflammation resolved and vision returned to 20/20 OU. A week later, she developed new fevers, headache, nausea, vomiting, seizures and altered mental status. She developed disseminated intravascular coagulopathy, and recurrence of maculopapular rash which progressed to toxic epidermal necrolysis (TEN). MRI of the brain demonstrated bilateral thalamic signal intensities. Extensive workup was again negative for bartonellosis, tularemia, rickettsioses, and rubeola. Normal studies included anti-NMDA, HSV, HHV-6, HHV-7, CMV, VZV, EBV, Mycoplasma, West Nile, Enterovirus, Typhus, HIV, NMO, MPO, PR-3, ANCA, ANA, HMPV, Adenovirus, Parainfluenza, Influenza. Parvovirus B19 CSF PCR was negative, but subsequent bloodwork had positive IgG and negative IgM, and positive serum PCR and bone marrow PCR at low levels with no pathologic evidence of acute parvovirus disease. Ferritin and soluble IL-2 were elevated, and natural killer cell count was low. A procedure was performed
Leopard Can't Change Its Spots - Path PPT
An 8 year-old Caucasian female presented with bilateral conjunctivitis, photophobia, and blurred vision. Visual acuity was 20/50 OD and 20/60 OS. She had 2-3+ anterior chamber cell and flare OU, 1+ vitreous cells OU, 2+ optic disc edema OU, and macular edema OU. She was diagnosed with anterior uveitis, vitritis, and neuroretinitis. At home, she had a cat, a rabbit, and a dog. She had recent travel to Hawaii. She reported a recent transient erythematous maculopapular rash behind her ears and neck. A full work-up was negative for bartonellosis, brucellosis, leptospirosis, toxoplasmosis, Lyme disease, and tularemia. Normal studies included serum ACE, lysozyme, ANA, chest x-ray, and HLA-B27. Systemic treatment consisted of azithromycin and rifampin. Prednisolone acetate eyedrops were added with a slow taper over 4 months when ocular inflammation resolved and vision returned to 20/20 OU. A week later, she developed new fevers, headache, nausea, vomiting, seizures and altered mental status. She developed disseminated intravascular coagulopathy, and recurrence of maculopapular rash which progressed to toxic epidermal necrolysis (TEN). MRI of the brain demonstrated bilateral thalamic signal intensities. Extensive workup was again negative for bartonellosis, tularemia, rickettsioses, and rubeola. Normal studies included anti-NMDA, HSV, HHV-6, HHV-7, CMV, VZV, EBV, Mycoplasma, West Nile, Enterovirus, Typhus, HIV, NMO, MPO, PR-3, ANCA, ANA, HMPV, Adenovirus, Parainfluenza, Influenza. Parvovirus B19 CSF PCR was negative, but subsequent bloodwork had positive IgG and negative IgM, and positive serum PCR and bone marrow PCR at low levels with no pathologic evidence of acute parvovirus disease. Ferritin and soluble IL-2 were elevated, and natural killer cell count was low. A procedure was performed
Leopard Can't Change Its Spots - Abstract
An 8 year-old Caucasian female presented with bilateral conjunctivitis, photophobia, and blurred vision. Visual acuity was 20/50 OD and 20/60 OS. She had 2-3+ anterior chamber cell and flare OU, 1+ vitreous cells OU, 2+ optic disc edema OU, and macular edema OU. She was diagnosed with anterior uveitis, vitritis, and neuroretinitis. At home, she had a cat, a rabbit, and a dog. She had recent travel to Hawaii. She reported a recent transient erythematous maculopapular rash behind her ears and neck. A full work-up was negative for bartonellosis, brucellosis, leptospirosis, toxoplasmosis, Lyme disease, and tularemia. Normal studies included serum ACE, lysozyme, ANA, chest x-ray, and HLA-B27. Systemic treatment consisted of azithromycin and rifampin. Prednisolone acetate eyedrops were added with a slow taper over 4 months when ocular inflammation resolved and vision returned to 20/20 OU. A week later, she developed new fevers, headache, nausea, vomiting, seizures and altered mental status. She developed disseminated intravascular coagulopathy, and recurrence of maculopapular rash which progressed to toxic epidermal necrolysis (TEN). MRI of the brain demonstrated bilateral thalamic signal intensities. Extensive workup was again negative for bartonellosis, tularemia, rickettsioses, and rubeola. Normal studies included anti-NMDA, HSV, HHV-6, HHV-7, CMV, VZV, EBV, Mycoplasma, West Nile, Enterovirus, Typhus, HIV, NMO, MPO, PR-3, ANCA, ANA, HMPV, Adenovirus, Parainfluenza, Influenza. Parvovirus B19 CSF PCR was negative, but subsequent bloodwork had positive IgG and negative IgM, and positive serum PCR and bone marrow PCR at low levels with no pathologic evidence of acute parvovirus disease. Ferritin and soluble IL-2 were elevated, and natural killer cell count was low. A procedure was performed
Intracranial Hypertension Induced by Megestrol Acetate Withdrawal
Intracranial hypertension has been associated with endocrine dysregulation in conditions such as obesity, pregnancy, oral contraceptive use, excess of Vitamin A, Addison disease, and corticosteroid use/withdrawal (1-6). Megestrol acetate (MA), commercially known as Megace, is a synthetic progesterone used as an appetite stimulant for cachexia secondary to cancer or AIDS and more recently used to treat failure to thrive (FTT) in the pediatric population (7-10). MA administration has been linked to adrenal insufficiency with variable clinical presentations (10-13). The use of MA in our patient links MA usage with intracranial hypertension