PIGT is one of over 29 glycosylphosphatidylinositol biosynthesis defect genes. Mutations cause genetically determined disorders characterized mainly by epilepsy with fever-sensitivity, central hypotonia, psychomotor delay and congenital malformations. The disease is known as multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) or glycosylphosphatidylinositol biosynthesis defect-7. Twenty-eight cases have been reported until today. We present seven novel Polish patients, all harboring 1582G>A variant in a homozygous or compound heterozygous state which seems to cause a milder phenotype of the disease. K E Y W O R D S antiepileptic drugs, developmental encephalopathy with epilepsy, fever-associated epilepsy, glycosylphosphatidylinositol biosynthesis defects, PIGT gene 1 | INTRODUCTION Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) are an emerging group of genetically determined disorders caused by a pathogenic variant of over 29 genes. 1,2 The first cases were described by Mabry et al in 1970 as familial cases of developmental delay (DD) and seizures with elevated serum alkaline phosphatase (ALP) concentration. 3,4 The majority of these disorders are characterized by intractable seizures, which occur during the neonatal period or infancy and are proceeded by hypotonia and psychomotor delay. Congenital malformations were also described in the literature. 2 These included diaphragmatic hernias in patients with PIGN-GPIBD variants and megacolon in patients with PIGV, PIGO and PGAP2 mutations. 1 Mutations in the PIGT gene were first described by Kvarnung et al in 2013. 5 The resulting syndrome, PIGT-GPIBD, is also known as multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) or GPIBD7 (MIM 615398). Since 2013, 28 cases have been reported, 6,7 while the largest cohort was reviewed by Bayat et al. 6 Patients Jezela-Stanek Aleksandra, Szczepanik Elżbieta and Mierzewska Hanna contributed equally to this work.

Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome is a rare disease (OMIM #618278) with only 10 cases described until now from six families (Uusimaa et al. 2018;Brodsky et al., 2020, Rapp et al., 2021. The reported cases carry variants in NHL repeat containing two gene (NHLRC2) (Biterova et al., 2018).In the first report, released in 2018, three Finnish patients were described (Uusimaa et al., 2018). In the second one, published in 2020, one Ukrainian patient was reported (Brodsky et al., 2020). These reports were followed by a recent publication of Rapp et al. (2021), reporting on six additional patients from three families. Patients with FINCA have multi-organ symptoms, which can be manifested along with feeding problems, growth failure, chronic

The main purpose of present review is to describe and organize autosomal recessive disorders (arachnomelia, syndactylism, osteopetrosis, dwarfism, crooked tail syndrome, muscular hyperplasia, glycogen storage disease, protoporphyria), which occur among beef cattle, and methods that can be applied to detect these defects. Prevalence of adverse alleles in beef breeds happens due to human activity—selections of favorable features, e.g. developed muscle tissue. Unfortunately, carriers of autosomal recessive diseases are often characterized by these attributes. Fast and effective identification of individuals, that may carry faulty genes, can prevent economical losses.

KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of −1 SDs to −2 SDs were noted in about half of the patients; only two patients presented with short stature below −3 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.

Germline variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) gene have recently been described in about 50 patients with developmental delay and cardiac, facial, and digital anomalies (CAFDADD). We aimed to depict further the clinical and genetic spectrum associated with TRAF7 germline variants in two additional patients, broaden the mutational spectrum, and support the characteristic clinical variety to facilitate the diagnostics of the syndrome among physician involved in the evaluation of patients with developmental delay/congenital malformations.