Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.

Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy-Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with CAPN15-related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy-Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy-Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15-related disease.

The clinical characteristics of primary headache and associated factors in children: A retrospective descriptive study.

BACKGROUND: Headache is the most encountered manifestation of pain in childhood. The purpose of this study was to investigate the incidence and clinical characteristics of primary headaches. Further, the factors associated with primary headache were examined. MATERIALS AND METHODS: A retrospective study was conducted among young children and adolescents over 3 years at a tertiary referral teaching hospital in North Jordan. Relevant patient information was obtained by reviewing patients' medical records. RESULTS: This study included 194 children (95 males, 99 females). The incidence rate of primary headache in the current study was 2.815 per 1000 children visited pediatric clinic. The mean age of patients at the time of headache onset was 10 years, and about half of them were males (95/194; 49%). Approximately 30% (56/194) had a family history of headache. Migraine headaches were the most commonly reported types (87/194; 44.8%) and only 17/194; 8.7% suffered from tension type headaches. Approximately, 40% (84/194) of patients reported severe headache and a third of them (67/194; 34.5%) complained of daily headaches. Pain location was reported as bilateral in most patients (153/194; 78.9%). About one fifth (41/194; 21.1%) stated that their headache was precipitated by sleep deprivation. Abnormal serum level of vitamin D and family history of headache were significantly associated with primary headache (p < 0.001). CONCLUSIONS: These findings highlight the importance of early detection and management of headaches among pediatric population. In addition, screening vitamin D status should be encouraged for children presented with primary headaches.

Ataxia-telangiectasia complicated by craniopharyngioma--a new observation.

Ataxia-telangiectasia is a rare autosomal recessive neurodegenerative disorder with high incidence of malignancy including leukemias, lymphomas, and solid tumors. Central nervous system tumors in ataxia telangiectasia include medulloblastomas and gliomas. We describe a 13-year-old girl with ataxia telangiectasia who developed craniopharyngioma and non-Hodgkin's lymphoma. To our knowledge, this is the first case of ataxia telangiectasia complicated by craniopharyngioma in the English literature.