De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser-Winter Syndrome.

Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser-Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (ß-actin) or ACTG1 (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated γ-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20/26 deafness, representing phenotypic expansion. The patient's exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that γ-actin c.542C > T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.

Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the ANKRD11 Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3.

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.

Secular trends in body height, body weight, BMI and fat percentage in Polish university students in a period of 50 years.

OBJECTIVES: The aim of the study was to determine changes in the magnitude and direction of secular trends in body height, body weight, body mass index (BMI) and fat percentage in university students from a university of technology and a university of physical education in a period of 50 years. METHODS: The data were derived from the examinations of male students from the Warsaw University of Technology, conducted four times, in 1959, 1971, 1994, 2011, and male students from the Józef Pilsudski University of Physical Education in Warsaw, who were examined in 1963, 1972, 1996, and 2012. Body height, body weight and thickness of 2 skinfolds (triceps skinfold and abdomen skinfold) were measured. Body mass index (BMI) and fat percentage (FAT%) were also calculated. RESULTS: Current university students are taller and heavier than their peers from the previous decades, with BMI remaining within the reference range. A substantial increase in fat percentage was found in both groups. Over the period of fifty years, mean fat percentage in students from the university of technology increased by 6.3% (F1,3 = 116.56, p < 0.001, η2 = 0.3736), whereas this increase in the students from the university of physical education rose by 3.5% (F1,3 = 72.94, p < 0.001, η2 = 0.3181). CONCLUSION: Changes in secular trends in the students from both universities are likely to be linked to the dynamic economic and systematic transformation in Poland observed in the period of the last 50 years. The period of economic transformations in the last decade was more conducive to physical development of university students than the previous period of economic crises.