Objective To observe and analyze the clinical characteristics of children with autosomal dominant hereditary microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability syndrome (MCLMR). MethodsA retrospective clinical study. In September 2023, the first patient and three family members (parents, brother) of MCLMR who were diagnosed through ophthalmic examination and genetic testing at Department of Ophthalmology of Henan Children's Hospital were included in the study. Clinical data were collected, inquired about medical history and family history in detail, and performed best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography (FFA), flash visual evoked potential (F-VEP), full field electroretinogram (ERG), cranial magnetic resonance imaging (MRI), and systemic examination. 3 ml of peripheral venous blood were collected from the proband, her parents and younger brother, and extracted whole genome DNA. Second generation sequencing technology was used for gene sequencing. For suspected pathogenic sites, Sanger sequencing was used for validation, and bioinformatics analysis was performed to determine the pathogenicity of the genetic variant sites. The relevant literature of PubMed of the National Library of Medicine and Wan Fang Med Online by computer were searched. The genetic characteristics and conducted literature review were summarized. ResultsThe proband (Ⅱ-1) was an 8-year-old and 5-month-old female. Her head was relatively small, the lower jaw was small, the ears protrude, the nose was wide, the eyelid was tilted upwards, philtrum was long. Mild intellectual disability, no history of lymphedema. The BCVA values for the right and left eyes were 0.08 and 0.1, respectively. Bilateral nystagmus. Atrophic lesioned in the macular area and below choroid retina of both eyes. FFA examination showed mottled fluorescent staining in the macular area and the below retina, with no obvious fluorescein leakage in the late stage. OCT examination revealed shallow macular fovea morphology, absence of ellipsoidal bands, unclear layers, thinning of the entire retina, and significant atrophy of the choroid and retina beneath the macula. F-VEP examination, no waveform was detected in both eyes. Full field ERG examination showed severe reduction in amplitude of a wave and b wave in both eyes. Head magnetic resonance imaging showed widening of the subarachnoid space in the left temporal region, with no significant abnormal signals observed in the brain parenchyma. Her father (Ⅰ-1) had mild nystagmus and strabismus. The phenotypes of the eyes of the mother (Ⅰ-2) and brother (Ⅱ-2) were not significantly abnormal. The genetic testing results showed that the proband (Ⅱ-1) had a heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of the KIF11 gene, which was a known mutation. Her parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) were both wild-type. The bioinformatics analysis results indicated that this mutation is a potentially pathogenic variant. A total of 109 cases were retrieved from 20 relevant literatures. Among them, 55 were male, 54 were females. There were 61 cases with family history and 48 cases without family history, respectively. Among the 109 cases, 98 cases (89.9%, 98/109) had microcephaly, 2 cases had premature closure of cranial sutures, and 11 patients underwent cranial MRI, which showed 11 cases of small head with simplified development of the cerebral gyrus. 50 cases (45.9%, 50/109) of lymphedema. 83 cases (76.1%, 83/109) of intellectual developmental disorders. 92 cases (84.4%, 92/109) had ocular abnormalities, 69 cases (63.3%, 69/109) had chorioretinopathy, 20 cases (18.3%, 20/109) had retinal folds, 10 cases (9.2%, 10/109) had nystagmus, and 17 cases (15.6%, 17/109) had retinal detachment. ConclusionsThe main clinical manifestations of MCLMR are microcephaly, chorioretinopathy, with or without lymphedema, and intellectual disability. The main manifestations of eye diseases are low vision, nystagmus, and chorioretinopathy. The heterozygous missense mutation c.895A>G (p.Ile299Val) in exon 8 of KIF11 gene is the pathogenic variant of this family.
ObjectiveTo observe and analyze the clinical characteristics of children who died of intraocular retinoblastoma (RB). MethodsA retrospective clinical study. Fourteen children (23 eyes) with intraocular RB who died after receiving treatment in Beijing Children's Hospital from 2009 to 2017 were included in the study. Among the children, there were 7 males (10 eyes) and 7 females (13 eyes); 5 had unilateral and 9 had bilateral tumor. Age were 17.2±15.5 months. All children underwent RetCam examination. RB was staged according to the international intraocular RB classify. Among the 23 eyes, 1 eye was in stage B, 2 eyes were in stage C, 12 eyes in stage D, and 8 eyes in stage E. Treatment methods included a systemic (vincristine, etoposide and carboplatin) chemotherapy (VEC chemotherapy), enucleation surgery, and vitrectomy. The basic conditions including age, time of diagnosis, pathological diagnosis, treatment and main causes of death were retrospectively analyzed. ResultsAmong the 14 cases, the first symptom was leukemia in 12 cases, red eye in 1 case, and squintin in 1 case. Systemic VEC chemotherapy was used for 1-6 courses of treatment; 5 cases were enucleated, 3 cases underwent histopathological examination; 3 cases were treated with vitrectomy. Among the 3 cases who underwent histopathological examination, the sclera and optic nerve, optic nerve and optic disc were invasted respectively. Seven patients died of tumor metastasis and/or intracranial lesions (50.0%, 7/14); the median survival time was 19 months. Four patients died of treatment (28.6%, 4/14), including 3 patients died of chemotherapy-related side effects, and 1 died of organ failure after enucleation surgery (7.1%); the median survival time was 3.5 months. Early abandonment of treatment died in 3 cases (21.4%, 3/14); the median survival time was 15 months. ConclusionIntracranial metastasis is the main cause of death in children with intraocular RB.