China
Africa
Explore chapters and articles related to this topic
Etiology and Prevalence of Obesity
Published in Claude Bouchard, The Genetics of Obesity, 2020
Four reports have documented cases of X-linked obesity, usually in association with severe mental retardation. Borjeson et al.25 reported an individual with X-linked reces-sively inherited obesity, severe mental retardation, hypogonadism with low or normal levels of gonadotropin, and short stature. Most of these cases have coarse facial features with large ears and microcephaly. In 1979 Vasquez et al.26 reported an X-linked type of obesity with profound mental retardation, true gynecomastia, and short stature with many other features similar to PWS, except for the mode of inheritance and the normal hands and feet. More recently, Young and Hughes27 reported four cases of X-linked mental retardation with short stature, obesity, and hypogonadism.27 Seizures were present in three of the four individuals, and mental tests revealed an IQ of approximately 25. Gonadotropins were high in these individuals, and testosterone, measured in one case, was low. In a recent publication, Wilson et al.28 have reported 14 males in three generations who have X-linked mental retardation, obesity, gynecomastia, speech difficulties, emotional lability, tapering fingers, and small feet. In contrast with the other reports, the mental retardation in these men was only mild to moderate. The gene is located near the centromere of the × chromosome. These cases are thus different from the three earlier ones.
Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
The sphingolipidosis disorders refer to a group of lysosomal storage disorders that in their classical form are notable for progressive and relentless neurological decline with relatively few other organ manifestations. In the severe forms of the conditions, onset is in infancy and is rapidly progressive over months leading to severe encephalopathy and death. These children usually have, albeit sometimes brief, a period of normal development followed by a plateauing of developmental progress and then actual regression. This may be exacerbated by intercurrent illness. Features such as epilepsy, macrocephaly, hyperacusis, visual impairment and spasticity are seen. The degree of irritability especially in Krabbe is extremely distressing to the family. There are no skeletal manifestations, usually minimal hepatomegaly (except in Niemann-Pick disease) and unlike in MPS disorders, coarse facial features are not seen. Retinal cherry red spots can sometimes be observed and loss of vision is common. The late infantile onset metachromatic leukodystrophy (MLD) has a very classical presentation whereby the previously near normal development plateaus at between 12 months to 2 years with subsequent aggressive regression and loss of any skills.
Genetic disorders, skeletal dysplasias and malformations
Published in Ashley W. Blom, David Warwick, Michael R. Whitehouse, Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Fergal Monsell, Martin Gargan, Deborah Eastwood, James Turner, Ryan Katchky
This condition presents in early childhood with short stature, and affected individuals tend to be less than the third percentile for height. Other generic features include characteristic ‘coarse’ facial features, thick inelastic skin, hepatosplenomegaly, neurological abnormalities and delayed intellectual development. Spinal abnormalities are common and include atlantoaxial instability with abnormal vertebrae producing a rigid kyphoscoliosis.
Herpes Simplex Conjunctivitis and Recurrent Chalazia in a Patient DOCK8 Deficiency
Published in Ocular Immunology and Inflammation, 2022
Tinh Le, Basak Can, Faruk Orge
Hyperimmunoglobulinemia E (Hyper-IgE) syndrome (HIES) is a rare hereditary immunodeficiency characterized by elevated serum IgE levels. The condition’s classical features are early-onset eczema and recurrent skin and pulmonary tract infections, typically caused by Staphylococcus aureus and Candida albicans.1,2 Various mutations, both autosomal dominant and recessive, can produce the phenotype of Hyper-IgE syndrome. Despite their different mechanisms with varied constellations of systemic manifestations, they all act by interfering with leukocyte chemokinesis and T-helper cell development.1 Heterozygous mutations in the STAT3 transcription factor gene are the most common cause of autosomal dominant (AD) cases, where skeletal and connective tissue abnormalities such as coarse facial features are frequent. Most autosomal recessive (AR) cases occur as a result of mutations in the Dedicator of Cytokinesis 8 (DOCK8) guanine nucleotide exchange factor (GEF), and clinical features of these patients include lower rates of skeletal abnormalities, higher rates of asthma and allergies, and higher rates of treatment-resistant, widespread cutaneous viral infections, often due to herpesviruses or HPV.3,4
Ophthalmologic and facial abnormalities of Nicolaides-Baraitser syndrome
Published in Ophthalmic Genetics, 2022
Russell Simmers, Allison Goodwin, Hind Al Saif, Natario Couser
NCBRS often presents with a very distinctive set of facial features. The most commonly reported facial findings include thick/everted lower lip (n = 69, 83.5%), coarse facial features (n = 58, 77.3%), wide/large mouth (n = 59, 74.7%), thin upper lip (n = 59, 74.7%), thick/anteverted alae nasi (n = 57, 73.1%), low frontal hairline (n = 47, 62.7%), upturned nasal tip (n = 49, 62.0%), broad philtrum (n = 47, 59.5%), long philtrum (n = 44, 56.4%), broad nasal base (n = 42, 55.3%), and broad nasal tip (n = 39, 52.0%) (Table 2). Other common findings include sparse scalp hair (n = 76, 95.0%) and microcephaly (n = 37, 52.1%). Some less common features may have been underreported in past literature. Broad nose was reported in 31.6% (6/19) of cases and depressed nasal bridge was reported in 26.3% (5/19) of cases since 2015, whereas neither were reported in the prior 61 cases.
Recent progress in gene therapies for mucopolysaccharidoses
Published in Expert Opinion on Orphan Drugs, 2018
Virginia Maria Ginocchio, Nicola Brunetti-Pierri
Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders caused by deficiencies of enzymes involved in degradation of glycosaminoglycans (GAG), also known as the ‘mucopolysaccharides’. Global incidence of MPSs is 1–4 cases in 100,000 live births [1]. In MPSs, undegraded GAG accumulate in the lysosomes of virtually every cell type resulting in multi-systemic clinical manifestations of variable severity. Affected patients present with coarse facial features, cardiac valve disease, respiratory disease, hepatosplenomegaly, bone dysplasia, and joint alterations (Table 1). Typically, MPS patients show relentless deterioration of their clinical manifestations as they usually appear normal at birth but progressively develop coarsening of facial features and developmental and cognitive decline. Primary central nervous system (CNS) involvement is present in the severe form of mucopolysaccharidosis (MPS) type I and II, in all MPS type III subtypes, and in MPS type VII. MPS type IV, VI, and IX lack of primary brain involvement [2] (Table 1). Mortality is high in the first two-three decades of life and it is largely related to respiratory infections, heart disease, and/or severe neurodegeneration [2,3].