A female case of 5,10-methenyltetrahydrofolate synthetase deficiency with novel neuro-imaging abnormalities.

BACKGROUND: Folate metabolism disorders can affect various organ systems, including the nervous system. 5,10-methenyltetrahydrofolate synthetase deficiency is a rare cerebral folate deficiency in which MTHFS activity is disrupted with low-normal cerebrospinal fluid (CSF) 5,10-methenyltetrahydrofolate levels, while peripheral folate levels are normal. CASE REPORT: We present here a female patient with developmental delay, microcephaly, hypotonia, nystagmus, and seizure in which a distinct brain MRI and CT showed restricted diffusion in the bilateral parietal and occipital lobes, and calcifications of the bilateral putamen, globus pallidus, and caudate nucleus, and the bilateral parietal and occipital lobes. Laboratory tests revealed macrocytic anemia, increased homocysteine, low-normal CSF 5,10-methenyltetrahydrofolate, and low CSF folate, but normal serum vitamin B12 and folate levels. A whole exome sequencing analysis verified the diagnosis of 5,10-methenyltetrahydrofolate synthetase deficiency. CONCLUSIONS: We have added novel knowledge which is nystagmus and hypotonia in the clinical findings, the involvement and restriction of bilateral putamen, globus pallidus, parietal and occipital lobes, and calcification of the bilateral putamen, globus pallidus, caudate nucleus, and parietal and occipital lobes in neuroimaging images and also low CSF folate in the metabolic investigation with the patient in 5,10-methenyltetrahydrofolate synthetase deficiency.

Understanding What You Have Found: A Family With a Mutation in the LAMA1 Gene With Literature Review.

INTRODUCTION: Cerebellar dysplasia with cysts (CDC) is an imaging finding which is typically seen with in individuals with dystroglycanopathy. One of the diseases causing this condition is "Poretti-Boltshauser Syndrome; PTBHS" (OMIM #615960). Homozygous or compound heterozygous mutations in the LAMA1 gene cause this disease. CASE PRESENTATION: 7 years old twin siblings consulted to the medical genetics department because of walking problems and cerebellar examination findings. MANAGEMENT AND OUTCOME: Clinical and radiological findings of the patient suggested a syndrome with recessive inheritance. Whole exome sequencing (WES) test was performed for definitive diagnosis. As a result of the patient's WES analysis, a homozygous mutation was detected in the LAMA1 gene. DISCUSSION: When determining the inheritance pattern of genetic diseases, if parents have consanquinity, this situation leads us to recessive inheritance diseases. Even if we are not consanquinity, but they say the same village, it is necessary to pay attention to the diseases of the recessive group. Whole exome sequencing analysis results in large amount of data generation. A good clinical evaluation is required to detect the mutation as a result of large data. To understand what we have found, we need to know what we are looking for.

Analysis of musculoskeletal dysmorphic abnormalities of 20 fetuses.

OBJECTIVES: This study aims to report rates of skeletal abnormalities and their risk factors in light of information obtained in a fetal autopsy series. PATIENTS AND METHODS: The study included 20 fetuses (11 males, 8 females and 1 ambiguous genitalia; mean age 19.3±4.0 weeks; range 16 to 32 week) who underwent autopsy in our hospital between January 2013 and March 2015. Fetuses were systematically classified according to age, gender, family history, abortus week, abortus type, and extremity and organ abnormalities. Skin biopsies were performed for genetic evaluation. Radiographic, pathologic and genetic findings were classified. RESULTS: Except one spontaneous abortus, all cases were applied medical abortus (94.1%). Genetic diagnosis could not be established in seven cases, whereas genetic disorders were identified in 13 cases: two trisomy 13, two trisomy 18, one (triploidi) 69,XXY, two arthrogryposis multiplex congenita, one osteogenesis imperfecta, one lethal multiple pterygium, one Saldino-Noonan syndrome, one teratogenic drug effect, one perinatal lethal hypophosphatasia, and one Beckwith-Wiedemann syndrome. Decreased fetal movement was one of the most frequently observed findings. Consanguineous marriage, oligohydramnios, drug addiction of the mother, teratogenic exposure, and other systemic abnormalities were risk factors. CONCLUSION: Skeletal dysplasias are rare diseases. Clinicians should be careful for skeletal abnormalities in perinatal period follow-ups.

A rare case of 3C disease: Ritscher-Schinzel syndrome presenting with recurrent talipes equinovarus.

INTRODUCTION: Club foot (CF) is characterized by multiple deformities such as varus, adductus and internal rotation of the forefoot. It is well-known and a frequent congenital disorder. CF can concurrently be seen with several diseases but it can rarely manifest as a component of any other syndrome. Ritscher-Schinzel syndrome, or cranio-cerebello-cardiac syndrome, is rarely seen and has autosomal recessive inheritance. It is characterized by cranio-facial, cerebellar and cardiac abnormalities. We report a case diagnosed as Ritscher-Schinzel syndrome concurrent with persistent CF. PRESENTATION OF CASE: A two-year-old boy with persistent CF and concurrent congenital hip dysplasia. Despite successful serial casting and subsequent achilloplasty a clinical relapse was observed in our patient. After a detailed phenotypic evaluation, genetical tests and imaging technique the patient was diagnosed 3C Ritscher-Schinzel syndrome. DISCUSSION: A comprehensive literature review did not show any reports about concurrent hip dysplasia and clubfoot in Ritscher-Schinzel syndrome. We report that CF may be associated with rare genetical abnormalities. CONCLUSION: With this report we would like to raise awareness about the possible association of persistent CF with this rare genetical disorder, Ritscher-Schinzel syndrome. It should be included in differential diagnosis of patients with persistent CF.