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Genetics
Published in Manoj Ramachandran, Tom Nunn, Basic Orthopaedic Sciences, 2018
Peter Calder, Harish Hosalkar, Aresh Hashemi-Nejad
Prader–Willi’s syndrome. This syndrome is caused by abnormalities in genes located in 15q11q13 (partial chromosome 15 deletion from father) and has an incidence of 1 in 12,000–15,000 newborns. The major clinical criteria are neonatal and infantile hypotonia, dolicocephaly (head length is longer than expected compared to the width, leading to a narrow face), almond-shaped eyes, hypogonadism and mild to moderate learning difficulties. Patients with Prader–Willi’s syndrome have hyperphagia, food foraging and an obsession with food. Hip dysplasia and scoliosis is also observed.
Sleep-Disordered Breathing in High-Risk Children
Published in Mark A. Richardson, Norman R. Friedman, Clinician’s Guide to Pediatric Sleep Disorders, 2016
PWS is a genetic disorder caused by loss of paternal genes located on chromosome 15. Children with PWS have severe infantile hypotonia, feeding difficulties, developmental delay, craniofacial abnormalities, and obesity. They often have sleep abnormalities including SDB. The causes of SDB in children with PWS include facial dysmorphism, hypotonia, and obesity. Adenotonsillar hypertrophy is a contributing factor (50).
Prader–Willi Syndrome: An Example of Genomic Imprinting
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
In 1993, Holm et al. (39) developed consensual diagnostic criteria to assist in the diagnosis of PWS using major and minor findings and established a scoring system for patients presenting with features seen in this syndrome. The scoring system consisted of three categories (major, minor, and supportive criteria) and scoring was based on a point system. The major criteria included infantile hypotonia, feeding problems, excessive or rapid weight gain, characteristic facial appearance (narrow face, dolichocephaly, almond-shaped eyes, small appearing mouth with thin upper lip), hypogonadism, global developmental delay, hyperphagia, and a 15q11–q13 deletion or maternal disomy 15 were weighed at one point each. Minor criteria such as decreased fetal movement or a weak cry, typical behavioral problems (temper tantrums, violent outbursts, stubbornness, manipulative, stealing), sleep disturbances, short stature for family background, hypopigmentation, small hands and feet, narrow hands with straight ulnar border, esotropia or myopia, thick, viscous saliva, speech articulation defects, and skin picking were weighed at one-half point each. Supportive criteria such as high pain threshold, reduced vomiting, temperature instability, scoliosis and/or kyphosis, early adrenarche, osteoporosis, unusual skills with jigsaw puzzles, and normal neuromuscular findings (EMG, NCV) received no points but may be helpful to confirm the diagnosis. Children of age ≤3 years required five points for diagnosis and four of the points should come from the major group. Children of age 3 years to adulthood required a total score of eight points necessary for the diagnosis. Major criteria comprised five or more points of the total score of eight.
Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population
Published in International Journal of Neuroscience, 2023
Dilsad Turkdogan, Ayberk Turkyilmaz, Gunes Sager, Gulten Ozturk, Olcay Unver, Merve Say
Recently, a broad clinical phenotype associated with genetic variants in components of the NALCN–UNC80–UNC79 ion channel complex regulating neuronal excitability was proposed as ‘autosomal-recessive NALCN channelopathies’ [34]. Biallelic variants in NALCN and UNC80 have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (OMIM: #615419) and 2 (OMIM: #616801), respectively. The novel splice-site variant of NALCN in our patient, is located in the donor splice-site of intron 35 and most probably affects splicing via alteration of the wild-type donor site. Epilepsy phenotype is variable in ‘NALCN channelopathies’. In a large series, Bramswig et al. [34] found early–onset epilepsy in 57% of patients with variants of NALCN and in 38% of patients with variants of UNC80. Generalized tonic clonic seizures at early childhood have been the most frequent type of seizure with variable response to antiseizure medications. The epilepsy phenotype in our patient with variant in NALCN was WS at onset evolving to LGS. In addition, he had novel dysmorphic features. The clinical phenotype of the patient with pathogenic variant in UNC80 was compatible with the OMIM phenotype. Genes related with ‘NALCN channelosomes’ would be linked to severe epilepsy/EIEE.
Improvement of Planning Abilities in Adults with Prader-Willi Syndrome: A Randomized Controlled Trial
Published in Developmental Neurorehabilitation, 2021
Séverine Estival, Virginie Laurier, Fabien Mourre, Virginie Postal
Prader-Willi Syndrome is a neurodevelopmental genetic disorder characterized by various expressions of endocrine, neurologic, cognitive and behavioral symptoms.1 The disorder is caused by the loss of expression of the imprinted genes from the 15q11q13 region of the paternal chromosome 15.2 Approximately 60% of cases are due to the deletion of the whole 15q11q13 region (type I deletion) or a part of it (type II deletion) and in 35% of cases, the entire 15th maternal chromosome is duplicated and the paternal chromosome is lost (uniparental maternal disomy).3 PWS is characterized by infantile hypotonia, mental retardation, feeding difficulty in infancy that evolves to an extreme drive to eat in childhood, dysmorphic features, short stature, hypogonadism, sleep apnea, diabetes, and severe maladaptive behaviors including obsessive, compulsive, and oppositional behaviors.4,5 Speech and language skills are also reported to be often impaired.6 Intellectual disability and deficit in executive functions are well documented in PWS: deficits in inhibition, switching, updating, cognition estimation, planning7–13 Executive functions (EF) are essential to allow a flexible and context-appropriate behavior when facing a new or complex situation.14,15 Planning is conceived as a higher cognitive function that implies the effective inhibition, updating and shifting processes.16
Genetic causes of nystagmus, foveal hypoplasia and subnormal visual acuity- other than albinism
Published in Ophthalmic Genetics, 2021
Miriam Ehrenberg, Laura Bagdonite-Bejarano, Anne B. Fulton, Naama Orenstein, Claudia Yahalom
This group comprised 14 individuals (patients 1–14, Tables 1 and 2), belonging to 11 families. The mean age was 14.6 years (STD ±19). Included were eight females, two pairs of siblings (subjects 6, 7 and 11, 12), a grandfather and grandson (subjects 13 and 14). Ten had a homozygous mutation; the others had compound heterozygous mutations. Seven had moderate visual impairment (BCVA range 20/80 to 20/125) and three had severe visual impairment (BCVA range 20/200 to 20/270). Refraction was variable; however, mild to moderate astigmatism was noted in almost all the patients (mean 1.9D). Four patients had additional systemic conditions: one had generalized joint hypermobility and infantile hypotonia; one had macrocephaly; one had hypospadias, patent foramen ovale, and delayed cognitive and motor development, (probably not associated with visual impairment); and the oldest patient had typical age-related diseases: hypertension and ischemic heart disease. One subject had bilateral posterior embryotoxon.