Chromosome Disorder

Chromosome disorders are secondary to structural or numeric chromosomal abnormalities involving the rearrangement or the loss or gain of a piece of a chromosome or the entire chromosome.

From: Rodak's Hematology (Sixth Edition) , 2020

Basic Genetic Principles

Fred Levine , in Fetal and Neonatal Physiology (Fifth Edition), 2017

Chromosomal Disorders

Chromosomal disorders fall into two general categories: those involving an incorrect chromosome number, called aneuploidy, and those that consequence from big chromosomal mutations, equally described before. Aneuploidy is the outcome of nondisjunction during meiosis, in which both members of a homologous pair of chromosomes move to the same daughter cell. As a outcome of nondisjunction, the fertilized egg receives either i or three copies of the chromosome instead of the usual 2. Because they involve numerous genes, with disturbance in the normal genomic balance, most disorders affecting chromosome number are embryonic lethal, particularly if the defect is loss of a chromosome. Disorders that are non lethal usually result in sterility, considering they foreclose meiosis from proceeding normally. The best-known and nigh common chromosomal disorder is Downwardly syndrome, which generally results from trisomy of chromosome 21 just as well tin exist due to a duplication or translocation of a specific region of chromosome 21. Trisomies of chromosome xiii or eighteen too occur only are much less mutual in alive born infants than is Down syndrome. Turner syndrome occurs in women who receive only a single X chromosome, whereas Klinefelter syndrome occurs in men who receive two Ten chromosomes in add-on to the Y chromosome.

Deletions that are too small to be visible using the cytogenetic techniques that were standard before the advent of molecular diagnostics are chosen microdeletions, and the resulting disorder is termed a microdeletion syndrome or contiguous gene syndrome. Microdeletions tin can be detected using large arrays of cloned genetic markers covering the entire genome. For some applications, the technique of fluorescence in situ hybridization (FISH) is however used. In the FISH technique, a cloned DNA probe is labeled with a fluorescent molecule and is then hybridized to a standard chromosome grooming on a microscope slide. The presence of 2 normal chromosomes can be visualized by the appearance of two fluorescent dots, whereas a heterozygous microdeletion appears as a single dot. Information technology is likely that avant-garde DNA sequencing technologies will supplant all previously used techniques for diagnosing genetic diseases, including microdeletions.

Examples of microdeletion syndromes are DiGeorge syndrome, characterized by T jail cell immunodeficiency and cardiac anomalies and due to a microdeletion of chromosome 22, and Prader-Willi syndrome, characterized past mental retardation, infantile hypotonia, and a compulsive eating disorder, and often due to a microdeletion of chromosome 15. A clinically unrelated disorder, Angelman syndrome, characterized past severe mental retardation, seizures, and a movement disorder, can also be due to a microdeletion in the same region of chromosome 15 as that affected in Prader-Willi syndrome. Nevertheless, in Prader-Willi syndrome, the deletion is always on the chromosome inherited from the father, whereas in Angelman syndrome, the deletion is always on the maternally inherited chromosome. Both Prader-Willi and Angelman syndromes can ascend from uniparental disomy, which means that both chromosomal homologues are derived from i parent, with no contribution from the other. For example, in approximately xv% of patients with Prader-Willi syndrome, both copies of chromosome 15 are maternally derived, whereas in Angelman syndrome, both copies can be inherited from the father.

Parent-of-origin effects on the occurrence of a genetic disease are a reflection of the phenomenon of imprinting. Imprinting refers to a process of transcriptional inactivation of a region of a chromosome derived from only one parent. The mechanism of this transcriptional inactivation involves methylation of cytosine residues during evolution. The reason for the existence of imprinting is non known, but it is clear that proper imprinting is necessary for normal development.

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General introduction to paediatric neurology

C deSousa , H Rattue , in Concrete Management in Neurological Rehabilitation (Second Edition), 2004

CHROMOSOMAL DISORDERS AND RECOGNISABLE PATTERNS OF MALFORMATION

Chromosomal disorders are caused by an aberration in an individual'due south complement of chromosomes. The normal situation is to possess 23 pairs of chromosomes, of which ane pair are sex activity chromosomes (two Ten chromosomes in females and an X and a Y in males). Individuals with Downwardly'south syndrome have an additional chromosome 21, with most having a total of 47 chromosomes. This disorder occurs in approximately 1 in 800 births and is more common with advancing maternal historic period (Jones, 1988). Children with Downwardly's syndrome have an increased likelihood of a diversity of congenital abnormalities, including cardiac malformations, intestinal atresias and cataracts. The intellectual evolution of children with Downwards's syndrome is slower than normal and the average IQ is around 50. Other specific neurological problems include hypotonia, an increased incidence of epilepsy and the occurrence of dementia from twoscore years onwards in many individuals.

Physiotherapy alone or as office of a multidisciplinary programme has been used in the direction of children with Down'due south syndrome. There is evidence for improvement in motor skills, particularly post-obit early-intervention programmes that include a serial of individualised therapy objectives (Harris, 1981; Connolly et al., 1984). Physiotherapy includes management of low muscle tone (see Ch. 25) and strategies to ameliorate force, co-ordination, general fitness and functional activities. Many children with Down's syndrome have asymptomatic atlantoaxial instability and effectually 1% are at increased risk of atlantoaxial subluxation, which may cause quadriplegia. Cervical spine radiographs are not carried out routinely in children with Down'south syndrome, but should be taken if at that place is head tilt or the emergence of neurological signs, or if participation in tumbling or contact sports is planned (American Academy of Pediatrics, 1995).

Other trisomies include Edward'south syndrome (trisomy 18) and Pattau's syndrome (trisomy 13), both of which cause profound retardation and usually expiry in early infancy.

Some chromosomal anomalies can be detected just by loftier-resolution chromosomal studies or by analysis of dioxyribonucleic acrid (DNA). Prader–Willi syndrome, for case, is due to a deletion of office of chromosome 15. Most affected infants are extremely hypotonic in the neonatal catamenia, often with marked feeding difficulties that require tube feeding. Later they take excessive appetites and obesity, short stature, and moderate learning difficulties. Considering of the hypotonia in that location is an increased risk of scoliosis in early on infancy and the function of physiotherapy includes providing advice nigh positioning and seating to promote good postures and reduce the risk of deformity developing.

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Nature and Frequency of Genetic Disease

Bruce R. Korf , ... Wayne W. Grody , in Emery and Rimoin'southward Principles and Exercise of Medical Genetics and Genomics (Seventh Edition), 2019

3.2.1 Chromosomal Disorders

A chromosomal disorder is classically divers as the phenotype resulting from visible alteration in the number or structure of the chromosomes. Using routine calorie-free microscopy and a moderate level of chromosome banding, the frequency of balanced and unbalanced structural rearrangements in newborns has been estimated at almost 9.2:1000 [8]. Some of those with unbalanced rearrangements will have built anomalies and/or intellectual disabilities. A proportion of those with balanced changes volition, in adult life, exist at increased run a risk of either miscarriage or having a disabled child. The incidence of aneuploidy in newborns is about 3:1000, but the frequency increases dramatically among stillbirths or in spontaneous abortions [9]. It is estimated that ane in two conceptuses has a chromosome abnormality, usually resulting in miscarriage [10]. Unlike types of chromosomal abnormalities predominate in spontaneous abortions compared with live-built-in infants. For example, trisomy 16 is the most common autosomal trisomy in abortions [11], whereas trisomies for chromosomes 21, 18, and xiii are the only autosomal trisomies occurring at appreciable frequencies in live-born infants. Monosomy for the X chromosome (45,Ten) occurs in most 1% of all conceptions, just 98% of those affected practice not reach term. Triploidy is also frequent in abortions but is exceptional in newborns. The high frequency of chromosomally abnormal conceptions is mirrored by results of chromosome analysis in gametes, which reveal an gauge abnormality rate of 4%–5% in sperm [12] and 12%–15% in oocytes [xiii]. When a family experiences three or more miscarriages, one parent is identified with an autosomal chromosome abnormality in viii.5% of analyses [xiv].

Routine light microscopy cannot resolve modest amounts of missing or additional material (less than iv   Mb of Deoxyribonucleic acid). The advent of cytogenomic microarray assay has revealed a loftier frequency of submicroscopic deletions and duplications and other copy number variations, including both apparently benign and pathological changes [15]. Multiple microdeletion and microduplication disorders have been defined in recent years, and undoubtedly more expect discovery. Such microdeletions, which epistemologically link "chromosomal disorders" with unmarried-gene disorders, account for a proportion of currently unexplained learning disability and multiple malformation syndromes [16,17].

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Female Reproductive System and Mammae1

Robert A. Foster , in Pathologic Ground of Veterinarian Disease (6th Edition), 2017

Sex activity Chromosome Disorders of Sexual Evolution.

True sex activity chromosome DSD is very rare. Cases of X_ (Turner syndrome) and XXY (Klinefelter syndrome) are reported. They ordinarily have gonadal dysgenesis and a female person phenotype. Chimerism is more common. Chimeras and mosaics have two or more somatic jail cell types, each with a dissimilar chromosome constitution. Chimeras have 2 genetically singled-out jail cell types that come from unlike individuals, whereas mosaicism is a different chromosomal constitution from altered mitosis. The most common bubble in domestic animals is the freemartin dogie (Fig. xviii-iii, B ). Blood vessels of the placentas from two different fetuses fuse and exchange blood between fetuses. Each fetus becomes a hematopoietic chimera. Anastomosis of placental vessels occurs most often in bovine species and less ofttimes in other ruminants and pigs. The freemartin is the female of a set of male and female person twins. Gene products from the cells of the male fetus induce fetal Sertoli cells and seminiferous cordlike structures in the ovaries of the female person twin. The ovaries are small and can have reduced number of or no germ cells. Some freemartins have ovotestes. The paramesonephric (Müllerian) duct derivatives vary from virtually normal to cordlike structures, only their lumens practise not communicate with the vagina. The vagina, vestibule, and vulva are hypoplastic. Vesicular glands are always present; other mesonephric (Wolffian) structures are nowadays to varying degrees. Externally, the animal has a female phenotype, but the vestibule and vagina are brusk, the vulva is hypoplastic, and the clitoris is enlarged. The male person twin is minimally affected.

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Ambiguous Ballocks

Selma Feldman Witchel , Peter A. Lee , in Sperling Pediatric Endocrinology (Fifth Edition), 2021

Sex activity chromosome disorders

45,X/46,XY Mosaicism

Most sex chromosome disorders, such equally 45,10 and cytogenetic variants and 47,XXY and cytogenetic variants, are not associated with aberrant external genital development and will not exist discussed in this chapter (run across Table 6.1). In contrast, individuals with 45,X/46,XY and 46,XX/46,XY karyotypes manifest a broad range of phenotypes. 108 Among individuals with 45,X/46,XY karyotype, internal and external genital structures range from normal male to ambiguous to female person. Whereas the typical histological features consist of poorly developed seminiferous tubules surrounded by wavy ovarian stroma, gonadal differentiation can range from normal testis to streak gonads. At the time of puberty, virilization can occur.

The majority of individuals identified by prenatal karyotype as existence 45,Ten/46,XY appear to exist normally androgenized males; all the same, individuals diagnosed postnatally tend to have more clinical signs. 109,110 A normal peripheral blood lymphocyte karyotype in individuals with gonadal dysgenesis suggests the presence of sexual activity chromosome mosaicism within the gonad(due south). 111 Individuals with sex chromosome DSDs because of gonadal dysgenesis have an increased risk of developing gonadal tumors, such as gonadoblastoma or dysgerminoma considering a dysgenetic gonad carrying a Y chromosome has an increased risk for neoplastic changes. Although gonadal tumors typically practise not develop until the second decade of life, they tin can occur at younger ages.

Among a serial of 63 males with 45,X/46,XY, subjects were classified into two groups; 1 group presented with genital anomalies and the second grouping presented with other reasons, such equally short stature or infertility. Individuals identified by genital anomalies tended to have lower rates of spontaneous pubertal development, shorter stature, and greater likelihood of germ jail cell neoplasia. 112 Although most gonads were classified as dysgenetic testes, some testes appeared relatively normal with evidence of spermatogenesis. No follicles were observed, suggesting that gonads labeled as ovotestis were mislabeled and consisted of undifferentiated/streak-similar tissue. 113 Based on these histological findings, it has been suggested that the etiology of the 45,X/46,XY karyotype is the loss of a Y chromosome in some cells. 114 Focal spermatogenesis was identified in approximately 25% of these subjects. Thus when gonadectomy is considered because of risk for neoplasia, fertility preservation should be considered. 112

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Pediatric Neurology Part I

Sameer Grand. Zuberi , in Handbook of Clinical Neurology, 2013

Introduction

Several hundred chromosomal disorders are associated with epilepsy and this number rises every year equally advances in cytogenetics and molecular genetics allow the detection of more than complex and smaller chromosomal re-arrangements, duplications, and deletions (Singh et al., 2002; Dibbens et al., 2009). Nonetheless at that place are relatively few weather in which epilepsy is a consistent feature and even fewer in which the electroclinical phenotype is recognizable (Tabular array 57.one). In these syndromes the seizure types and EEG features can propose a specific diagnosis and guide the clinician to the appropriate genetic investigation.

Table 57.i. Disorders consistently associated with epilepsy

Disorders Estimated incidence
Terminal deletion chromosome 1p36 ane in 5000
Wolf–Hirschhorn syndrome (4p-) 1 in 50   000
Angelman syndrome one in xv   000
Inversion duplication 15 syndrome (IDIC 15) 1 in 30   000
Miller–Dieker syndrome (del 17p13.3) 1 in 300   000 (estimates)
Band fourteen syndrome Unknown
Band 20 syndrome Unknown

Cytogenetic tests can look at the chromosome in varying degrees of item. Loftier resolution G banding of the karyotype volition pick up major lesions in much more detail than a decade ago. Fluorescent in situ hybridization (FISH) probes can exist targeted to the gene-rich, telomeric regions of chromosomes and Dna dosage techniques such every bit multiplex ligation probe amplification (MLPA) or comparative genome hybridization (CGH) have the ability to notice micro-chromosomal lesions (Slavotinek, 2008). Many chromosomal anomalies are mosaic and diagnosis can be made from peel biopsy when lymphocyte studies are negative (Fig. 57.i).

Fig. 57.1. A 2-year-old girl had refractory absences and dysmorphic features. Karyotype from lymphocyte preparation was normal. Peel biopsy revealed diploid–triploid mosaicism in fibroblasts.

The mechanisms through which chromosome lesions produce epilepsy are not well understood but are likely to be varied and complex. Malformations of cortical development can be consistently associated with chromosomal lesions such every bit the 17p13.3 deletion and Miller–Dieker lissencephaly, or rarely such as focal polymicrogyria and 22q11 deletions. Still the conditions discussed in this chapter are non associated with any consistent neuroimaging or neuropathological findings which may help to explain the development of epilepsy.

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Disorders of Growth

ADDA GRIMBERG , DIVA D. DE LEÓN , in Pediatric Endocrinology, 2005

Genetic and Chromosomal Disorders

Genetic and chromosomal disorders are known causes of tall stature. Hyperploidy of sex chromosomes predisposes to tall stature. The most common of these disorders is Klinefelter syndrome (47,XXY), which is the nearly common sex activity chromosome disorder, affecting 1:500 males. Affected males conduct an additional Ten chromosome, which results in male hypogonadism, androgen deficiency, and impaired spermatogenesis. Another characteristics include gynecomastia, small testes, sparse body hair, tallness (long-legged proportions), and infertility. In children with Klinefelter syndrome, the tendency toward alpine stature becomes evident starting at 5 to 6 years of age; of note, however, men with Klinefelter syndrome ordinarily accept normal adult stature. The definite diagnosis of Klinefelter syndrome is fabricated with a karyotype, but a careful history and concrete examination, with the authentication being small-scale, business firm testes, would provide sufficient diagnostic clues to make the practitioner doubtable the diagnosis. Therapy for patients with Klinefelter syndrome consists of testosterone replacement to correct the androgen deficiency and give the patients appropriate virilization. This therapy cannot reverse infertility.

Children with 47,XYY syndrome are normal sizes at birth, with no congenital defects. The mean adult height in one series was 189 cm, and in other series, final heights of the patients have been greater than the heights of their siblings. Genitalia are normal and plasma testosterone concentrations are in the high-normal ranges. The average IQ is reduced. The diagnosis tin be made only past karyotype.

The prototypic genetic syndrome associated with tall stature is Marfan syndrome, an autosomal dominant connective tissue disorder. Marfan syndrome has diverse and even seemingly unrelated manifestations in dissimilar organs arising from a single mutation in the fibrillin factor (FBN1) at chromosome 15q21. Organs involved include the skeleton, optics, cardiovascular arrangement, skin, integument, lungs, and muscle tissue. Diagnosis of Marfan syndrome is largely clinical and pragmatic. Classically, Marfan syndrome is characterized by hyperextensible joints, dislocation of the lens, kyphoscoliosis, mitral valve prolapse, and aortic dilatation and autopsy. Patients with Marfan syndrome have long, thin basic that result in arachnodactyly and moderately tall stature with long-legged proportions. Because of the possible lethal complications of the cardiovascular manifestations of Marfan syndrome, awareness of the classic features for early diagnosis by the master doctor is important. Among causes of sudden death among competitive athletes, Marfan syndrome trails behind only hypertrophic cardiomyopathy, built anomalies of the coronary arteries, and occlusive coronary illness. Any state of affairs that results in greater catecholamine release increases inotropy and, every bit a event, the impulse of blood ejected into the aorta, with the take a chance of dissection of the aorta. Therefore, information technology is recommended that patients avert situations of considerable emotional or physical stress. It is currently recommended that all patients with Marfan syndrome exist considered for β-adrenergic blockade, because this is believed to have a protective effect from both aortic dilatation and dissection, but this has yet to be conclusively proved. Techniques for repairing all aspects of cardiovascular disease in Marfan syndrome have undergone rapid evolution and today, corrective surgery for the mitral valve and the aortic root (dissected and not dissected) carries a lower risk for the majority of the patients. In regard to the tall stature, treatment with estrogen or testosterone has non been systematically tested for efficacy or toxicity, so its use to reduce ultimate summit should be done with caution.

Homocysteinuria, an autosomal recessive disorder of methionine-homocysteine metabolism, is associated with marfanoid features but may too involve mental retardation, seizures, joint contractures, and a tendency for thromboembolism. Early on diagnosis by amino acid studies and dietary treatment can prevent mental retardation.

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Rare Childhood Lung Disorders

Daniel Bottom Dr. , ... James South. Hagood Doc , in Kendig'due south Disorders of the Respiratory Tract in Children (Ninth Edition), 2019

Clinical Features

A number of chromosomal disorders are associated with PL, including Noonan syndrome, Hennekam syndrome, yellow nail syndrome, and Down syndrome. 1,iii Children with PL associated with chromosomal disorders are more likely to present with generalized lymphangiectasia. These patients may display a less severe pulmonary component and may take a better prognosis when compared with those who present with primarily pulmonary disease during the neonatal menses. one

At birth, infants with PL often present with respiratory distress that progresses quickly to respiratory failure. one Chylous pleural effusions may exist prominent, simply a significant number of children with PL do not nowadays with effusions. ane Individuals who first develop symptoms later in infancy or during childhood usually brandish less severe disease when compared with those with neonatal onset. In later-presenting forms, initial symptoms include chronic tachypnea, recurrent cough, and wheezing. 4 PL in these individuals has been associated with chylothorax, chylopericardium, and chylous ascites. 3 These patients have frequent respiratory exacerbations, peradventure related to lower respiratory tract infection that leads to transient worsening of lymphatic drainage. ane,4

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Cardioskeletal Muscle Disease Associated With Chromosomal Disorders

S.R. Lalani , in Cardioskeletal Myopathies in Children and Young Adults, 2017

Down Syndrome (Trisomy 21)

At birth, chromosomal disorders are ascertained in 1/160 live born infants [9]. Of these, the most common aberration is Down syndrome (MIM #190685) seen in 1/800 live births. The extra chromosome 21 (trisomy 21) observed in nearly 95% of these individuals arises predominantly from nondisjunction during maternal meiosis I. The incidence of Down's syndrome is much higher in mothers 35   years of age or older. Well-nigh iv% of individuals with Down syndrome take 46 chromosomes, with a Robertsonian translocation between chromosome 21q and the long arm of 1 of the acrocentric chromosomes (such every bit 14 or 22). The recurrence risk is significant in this group if the parent is a carrier of the translocation. The clinical diagnosis of Down syndrome can usually be made at birth in the presence of characteristic features, including upslanting palpebral fissures, bilateral epicanthal folds, flat nasal bridge, small ears, and hypotonia [10]. Down's syndrome is the single near common genetic cause of intellectual disability. Malformations such equally duodenal atresia and Hirschsprung are more common than in other disorders. Cardiac screening is recommended in all infants with Down's syndrome, since 45–50% of the afflicted individuals are known to have cardiac defects [11]. Intervention with surgical correction of CHD has significantly decreased mortality in infants with Down syndrome [12]. AVSD is the most common cardiac defect, seen in 30–40% [13,14], followed past ventricular septal defect (VSD), atrial septal defect (ASD), and tetralogy of Fallot (TOF) [15]. Less common defects include coarctation of the aorta (CoA), PS, vascular ring, and defects of single ventricle physiology [16,17]. Children with Down syndrome are also considered to be at a higher risk for developing persistent pulmonary hypertension of the neonate (PPHN), even in the absence of structural heart disease [18]. Weijerman et al. [19] observed an incidence of ~5% for PPHN in newborns with Down syndrome, as compared to 0.1% in the general population (p<.001).

The genetic mechanism related to CHD is believed to be cistron dosage alteration through duplication of an extended region on chromosome 21 (HSA21) [20]. Barlow et al. [21] mapped this disquisitional region to a 5.27-Mb segment involving 82 genes. This region, specific for endocardial cushion defects was afterward narrowed down to a two.eight   Mb interval on chromosome 21 [22].

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Neurologic Complications of Congenital Heart Disease and Cardiac Surgery in Children

Catherine Limperopoulos , Adré J. Du Plessis , in Aminoff's Neurology and Full general Medicine (Fifth Edition), 2014

Chromosomal Disorders

A number of chromosomal disorders have a phenotype that includes both cardiac and neurologic malformations, including trisomies 11, 18, and 21. The most common neurologic manifestation in children with trisomy 21 (Down syndrome) is cerebral dysfunction. Epilepsy develops in approximately 5 percent of these children, and built heart defects, most normally endocardial cushion defects, are present in 40 percent of children with Down syndrome. Gross structural encephalon alterations in Downwards syndrome include a narrow superior temporal gyrus and a disproportionately small cerebellum and brainstem. 24 Trisomy 13 is associated with ventricular septal defects and patent ductus arteriosus; the associated cerebral dysgenesis in this syndrome is often astringent, with holoprosencephaly and agenesis of the corpus callosum being the near common lesions. The most common cardiac lesions in infants with trisomy 18 are ventricular septal defects and patent ductus arteriosus, with neuronal migration defects being the most common grade of brain dysgenesis. 34

The phenotypic spectrum of specific chromosome 22 deletions, particularly in the 22q11 region, includes a diversity of cardiac malformations and neurologic features. 35 Recent population-based data propose that at to the lowest degree 700 infants with chromosome 22 deletion syndromes are born annually in the United States. 36 The acronym Catch 22 (cardiac defect, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, and chromosome 22q11 deletions) has been used to designate this group of related syndromes. The two most common, DiGeorge and velocardiofacial (or Shprintzen) syndromes, accept neurologic and cognitive manifestations in association with structural cardiac defects. 37 The central problem in DiGeorge syndrome is a developmental defect of the third and fourth pharyngeal pouches, manifesting with thymic and parathyroid hypoplasia forth with conotruncal cardiac malformations, which include an interrupted aortic curvation (type B), truncus arteriosus, and tetralogy of Fallot.

A common neurologic presentation in both the DiGeorge and the velocardiofacial syndromes is hypocalcemic seizures due to hypoparathyroidism. In addition to the usual cardiac lesions (i.e., ventricular septal defect or tetralogy of Fallot), the velocardiofacial syndrome is associated with cleft palate or velopharyngeal insufficiency and a typical facial advent, including a broad, prominent nose and retrognathia, forth with microcephaly in up to 40 percent of cases. Neuroimaging and autopsy studies may demonstrate a small posterior fossa and vermis, small cystic lesions adjacent to the frontal horns of the lateral ventricles, dysgenesis of the corpus callosum, and abnormal cortical gyrification patterns. 38,39 Delayed opercular development and disproportionately enlarged sylvian fissures with white matter abnormalities might underlie some of the developmental problems in these children. twoscore,41 The mean intelligence caliber (IQ) in this syndrome is effectually lxx, with balmy to moderate cognitive bug nowadays in up to 50 percent of patients. 37,41

In recent years, a high rate of autism spectrum disorders and attending deficit/hyperactivity disorder has been described in this group of patients. 42,43 Psychiatric disorders occur in upwards to 22 percent of those with 22q11 deletion syndromes. 38,39 A peculiar and inappropriately blunt upshot may be evident during childhood, often evolving to frank psychosis during adolescence and machismo. 44 Contradistinct prefrontal cortex-amygdala circuitry, reduced cerebellar and thalamic volumes, and increased basal ganglia and corpus callosal volumes, equally shown by quantitative neuroimaging studies, may underlie disrupted emotional processing and course the neurobiologic substrate for the psychiatric disturbances in these children. 41,45–47

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