Midline defects in the brain may be related to genetic syndromes. Association with facial anomalies and skeletal deformities has been described. In the present case, a routine second trimester scan revealed cerebral abnormalities (corpus callosum agenesis, cerebellar cleft due to vermian hypoplasia, ventriculomegaly), suspected cortical developmental disorder, hypertelorism, a hypoplastic nasal bone, a small median cleft lip and palate, abnormal facial profile, as well as syndactyly of the left hand involving the fourth and fifth finger. Genetic testing revealed a normal karyotype. Subsequent trio exome sequencing did not identify any pathogenic variants or variants of unknown significance. The vaginal delivery at term and postnatal adaptation were uneventful. Postnatal neurosonographic imaging and clinical evaluation confirmed the prenatal findings. Both mother and child were discharged in healthy condition with scheduled follow-ups. Differential diagnoses of the present anomalies include Hartsfield-Bixler-Demyer Syndrome, Oro-Facial-Digital-Syndromes, Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate Syndrome and Acrocallosal Syndrome. Invasive diagnostic and genetic testing are recommended when multiple fetal anomalies suggest a potential genetic syndrome. While not all cases reveal an underlying genetic cause, prenatal findings can provide valuable information to help parents and healthcare providers make informed decisions about the continuation of the pregnancy.

Mutations in the KIF7 gene have been implicated in autosomal recessive conditions such as Joubert syndrome, acrocallosal syndrome, and fetal hydrolethalus, as well as in retinal degeneration and other ocular manifestations due to their effect on primary cilia. In this study, we report that the full-field electroretinogram (ERG) test showed non-recordable scotopic ERG responses, while photopic ERG responses were diminished bilaterally. This is a case report of a 62-year-old female patient with painless, progressive vision loss in both eyes. Fundus examination revealed a pale optic nerve head, vessel attenuation, and macular thinning without peripheral pigmentary changes. The full-field electroretinogram (ERG) test showed non-recordable scotopic ERG responses, while photopic ERG responses were diminished bilaterally. Based on these ocular findings, the patient was clinically diagnosed with retinitis pigmentosa (RP) sine pigmento. Genetic testing identified a pathogenic heterozygous mutation in the KIF7 gene with the variant c.61C>T (p.Arg21*). Our case suggests that this pathologic variant may be associated with RP sine pigmento. Further studies are warranted to better understand the role of the KIF7 gene in retinal dystrophies.

The purpose of this review article is to outline the natural history, pathogenesis, anatomic considerations and surgical decision-making in caring for patients with intracranial arachnoid cysts. A review of the literature for intracranial arachnoid cysts was performed using Embase, PubMed, and Web of Science databases, including review of the bibliographies of eligible articles and the author's own experience. Among those reviewed, 59 relevant original articles were included as well as illustrative cases from the authors own experience. Arachnoid cysts are congenital lesions characterized by split arachnoid membrane, thick collagen in the cyst wall, absent traversing trabecular processes within the cyst, and hyperplastic arachnoid cells in the cyst wall. The underlying etiology is not entirely known, and they occur in greater proportion in males and in greater incidence with various genetic conditions including Down syndrome, mucopolysaccharidosis, schizencephaly, neurofibromatosis, autosomal dominant polycystic kidney disease (ADPKD), acrocallosal syndrome, and Aicardi syndrome. Most intracranial arachnoid cysts are incidentally found and occur in the middle cranial fossa, with the remaining occurring in the cerebellopontine angle, suprasellar cistern, quadrigeminal cistern, convexity, and posterior fossa/cisterna magna. The current article outlines the natural history, prevalence, demographic factors, and treatment decisions in managing patients with intracranial arachnoid cysts.

Arachnoid cysts (ACs) are the most common space-occupying lesions in the human brain and present significant challenges for clinical management. While most cases of ACs are sporadic, nearly 40 familial forms have been reported. Moreover, ACs are seen with increased frequency in multiple Mendelian syndromes, including Chudley-McCullough syndrome, acrocallosal syndrome, and autosomal recessive primary ciliary dyskinesia. These findings suggest that genetic factors contribute to AC pathogenesis. However, traditional linkage and segregation approaches have been limited in their ability to identify causative genes for ACs because the disease is genetically heterogeneous and often presents asymptomatically and sporadically. Here, we comprehensively review theories of AC pathogenesis, the genetic evidence for AC formation, and discuss a different approach to AC genomics that could help elucidate this perplexing lesion and shed light on the associated neurodevelopmental phenotypes seen in a significant subset of these patients.

The kinesin-4 member KIF7 plays critical roles in Hedgehog signaling in vertebrate cells. KIF7 is an atypical kinesin as it binds to microtubules but is immotile. We demonstrate that, like conventional kinesins, KIF7 is regulated by auto-inhibition, as the full-length protein is inactive for microtubule binding in cells. We identify a segment, the inhibitory coiled coil (inhCC), that is required for auto-inhibition of KIF7, whereas the adjacent regulatory coiled coil (rCC) that contributes to auto-inhibition of the motile kinesin-4s KIF21A and KIF21B is not sufficient for KIF7 auto-inhibition. Disease-associated mutations in the inhCC relieve auto-inhibition and result in strong microtubule binding. Surprisingly, uninhibited KIF7 proteins did not bind preferentially to or track the plus ends of growing microtubules in cells, as suggested by previous in vitro work, but rather bound along cytosolic and axonemal microtubules. Localization to the tip of the primary cilium also required the inhCC, and could be increased by disease-associated mutations regardless of the auto-inhibition state of the protein. These findings suggest that loss of KIF7 auto-inhibition and/or altered cilium tip localization can contribute to the pathogenesis of human disease.