holoprosencephaly trisomy 18

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Child with Holoprosencephaly. In addition to trisomy 13, several other chromosomal abnormalities, including trisomy 18, trisomy 13-15, trisomy 13-15 mosaicism, ring chromosome 13 or 18, and chromosomal deletion 13 or 18, have been identified in patients with HPE. 2012), and is often associated with malformations of midline structures. HPE can be seen in association with trisomy 13, trisomy 18, or triploidy. Holoprosencephaly, once called arhinencephaly, consists of a spectrum of defects or malformations of the brain and face. Trisomy 18 and 13 are usually caused by spontaneous genetic mutations that occur at the time of fertilization. Approximately 30% to 50% of live births with HPE have chromosomal abnormalities, but this is likely an overestimation based on underreporting of milder cases. The presence of large dorsal cysts, hydrocephalus, or midline craniofacial defects may provide clues that eventually lead to the recognition of the associated HPE. Diabetes insipidus is particularly frequent, growth hormone deficiency, hypocortisolism, and hypothyroidism also may occur. What causes trisomy 18 and trisomy 13? Polyalanine and Polyglutamine Diseases: Possible Common Mechanisms? However, with the improved understanding of phenotypes and genetics of HPE, there is a growing appreciation that HPE is a multi-factorial disease spectrum that requires not only a genetic mutation within a certain locus, but also an interaction of this mutation with factors within the patients genetic background and perhaps environmental insult (Roessler and Muenke, 2010). Edwards' syndrome affects how long a baby may survive. This is our Daughter Everly's Journey. This may have been due to the identification of only the most severe cases. A mild version of HPE called middle interhemispheric variant of HPE has also been identified.9, E.S. They may also have an underlying endocrine deficiency, requiring assessment and treatment. When this happens, it can affect facial features and cause defects such as: cleft lip and palate an abnormally small eye or eyes (microphthalmia) absence of 1 or both eyes (anophthalmia) reduced distance between the … Severe developmental delay is present in alobar HPE. In many cases, it appears to be the consequence of a genetic or an environmental disruption of the sonic hedgehog (SHH) signaling pathway, which is responsible of the specification of the neural tube but also plays a role in the proliferation of neural progenitors in the ventricular zone of the telencephalon. Phadke and Thakur reported on a case of iniencephaly and alobar holoprosencephaly with trisomy 13 mosaicism , which was very similar to our case. Developmental disability affects nearly all patients with HPE. Chromosome analysis demonstrated an abnormal karyotype 46,XX,i(18)(q10). Approximately one-half of all cases of holoprosencephaly have a chromosomal cause. Everly was diagnosed with Alobar Holoprosencephaly & Trisomy 13 when I was around 12 weeks pregnant. home/medterms medical dictionary a-z list / holoprosencephaly definition. The risk of reoccurrence is small in most families. The abbreviated term ADHD denotes the condition commonly known as. Motor difficulties and dystonia may be partially responsive to trihexyphenidyl. Figure 4. Clinicians usually adhere to the dogma that “the face predicts the brain.” That is, the severity of the facial malformation is indicative of the severity of the brain defects. Any child with holoprosencephaly deserves a full genetic evaluation so that appropriate genetic counseling and recurrence risks can be given to the families. A small subset of the children are of normal intelligence, and those cases are managed as any cleft lip and palate child. The root cause of holoprosencephaly occurs very early in embryonic development, with disturbances in the ability of the prechordal plate and anterior endoderm to secrete sonic hedgehog (shh) and other factors required for induction and early development of the ventral forebrain. Search results ... Trisomy 13 Patau's syndrome ... 18 … Terms of Use. Alobar holoprosencephaly is the most serious form because the brain fails to separate and is usually associated with severe facial anomalies. Sadly, most babies with Edwards' syndrome will die before or shortly after being born. Edwards' syndrome, also known as trisomy 18, is a rare but serious condition. The sine qua non of HPE is incomplete cleavage of midline structures involving the telencephalon and diencephalon. Other midline anomalies, such as agenesis of the corpus callosum, absence of the septum pellucidum, and hydrocephalus with communication of the lateral ventricles, are sometimes misdiagnosed prenatally as HPE (Fig. Our daughter, Lily Grace, was born to heaven on June 6, 2010. • Rosa RFM et al. Electrolyte screening should be performed for diabetes insipidus surveillance. Most models are transgenic mouse or fish lines that represent various subclasses of HPE. These loci and genes represent signaling pathways that play an essential role in forebrain and facial development. Seizures and mental retardation may occur. Gastrostomy tubes often are necessary to address the complex management issues of ensuring adequate calories related to feeding dysfunction and delivery of adequate free water necessary for management of diabetes insipidus. The GPI-anchored protein TDFG1 and the transcription factor FoxH1 (forkhead box H1) function in the Nodal pathway and have also been linked to HPE (Roessler et al., 2008; McKean and Niswander, 2012). HPE is typically associated with midline facial anomalies. The frontal horns of the lateral ventricles are not developed, but the posterior horns are present. Reduction defects of the nose can also be components of this condition. Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some or all of the cells of the body contain extra genetic material from chromosome 13.The extra genetic material disrupts normal development, causing multiple and complex organ defects. Meckel's syndrome is an autosomal recessive condition. Holoprosencephaly is caused by a failure of the embryo's forebrain to divide to form bilateral cerebral hemispheres (the left and right halves of the brain), causing developmental defects of the face and in brain structure. 26-3). Amniocentesis revealed Trisomy 18, and the patient underwent a vaginal delivery at 22 weeks of gestation. Patients with this anomaly frequently exhibit specific craniofacial anomalies, including midline facial clefts, cyclopia, and nasal anomalies. Monuki, in Encyclopedia of Neuroscience, 2009. The proximity of the FNP and the developing forebrain allow for molecular signals emanating from the forebrain neuroectoderm to affect FNP growth and development. This is known as holoprosencephaly. Specifically, signals from the forebrain are hypothesized to affect the proliferation/survival of neural crest-derived cranial mesenchyme within the FNP. From: Swaiman's Pediatric Neurology (Sixth Edition), 2017, J.A. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL: https://www.sciencedirect.com/science/article/pii/B9780080450469014856, URL: https://www.sciencedirect.com/science/article/pii/B9780323445481000395, URL: https://www.sciencedirect.com/science/article/pii/B9780080450469010779, URL: https://www.sciencedirect.com/science/article/pii/B9780444528919000130, URL: https://www.sciencedirect.com/science/article/pii/B978012369462150034X, URL: https://www.sciencedirect.com/science/article/pii/B9780123708779000232, URL: https://www.sciencedirect.com/science/article/pii/B9780323371018000266, URL: https://www.sciencedirect.com/science/article/pii/B9780124059450000351, URL: https://www.sciencedirect.com/science/article/pii/B9780128012383054519, Swaiman's Pediatric Neurology (Sixth Edition), 2017, Obstetric Imaging: Fetal Diagnosis and Care (Second Edition), Forebrain Development: Holoprosencephaly (HPE), Sandrine Passemard, ... Alain Verloes, in, Bendavid et al., 2010; Roessler and Muenke, 2010. Ethmocephaly is the least common facial anomaly. Occasionally, isolated neuronal heterotopias are seen, particularly in the middle interhemispheric variant. Holoprosencephaly (HPE) is a birth defect in which the telencephalic vesicles emerging from the forebrain during the 5th and 6th week of development remains fused on the midline. Ching-Fang Chang, ... Samantha A. Brugmann, in Principles of Developmental Genetics (Second Edition), 2015. For example, if a baby is born with three #21 chromosomes, rather than the usual pair, the baby would be said to have \"trisomy 21.\" Trisomy 21 is also known as Down syndrome. Those that present to a clinician typically have hypotelorism (narrowed midface with close set eyes), a midline cleft lip and/or palate with a small to nonexistent central strut of the nose (columella). Terms of Use. Several chromosomal abnormalities are asso-ciated with alobar holoprosencephaly, with the most fre-quent being trisomy 13; others include trisomy 18, trisomy 13/15 and partial monosomies of 13q and 18q2. At the mild end of the spectrum is the presence of a single central incisor (one upper front tooth rather than the usual two). Holoprosencephaly (HPE) is a heterogeneous central nervous system ... Trisomy 18 is less commonly seen in conjunction with HPE and accounts for 1% to 2% of the cases. It is subdivided into three groups based on the degree of cleavage between the hemispheres (Cohen, 2001). Typically, in the first few weeks of pregnancy, the developing embryo begins laying the structural groundwork for brain development. HPE demonstrates significant variation in severity and manifestations (variable expressivity), meaning that two people with the same genetic predisposition to HPE can have significantly different physical features. The best diagnostic procedure is a brain scan (CT or MRI). HPE is associated with structural abnormalities of the midface. Early death is typical for most cytogenetically abnormal children and those individuals with the most severe facial features (cyclopia or ethmocephaly). Maternal diabetes is an environmental cause of HPE. At least nine genes have been associated with HPE, including: SHH (7q36); ZIC2 (13q32); SIX3 (2p21); TGIF (18p11.3); PATCHED-1 (9q22); GLI2 (2q14); DISP1 (1q24); NODAL (10q); and FOXH1 (8q24.3). Trisomy 18 (T18), Edwards' syndrome, is one of the two most common autosomal aneuploidies in humans, second to Down syndrome (trisomy 21; Hui et al. At the most severe end of this spectrum are cases involving serious brain malformations, some so severe that they are incompatible with life and often cause spontaneous intrauterine death. Trisomy 18 and holoprosencephaly Rafael F. M. Rosa Clinical Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil To learn more about our experience, you may want to start at the beginning. Taken together these examples support a hypothesis that any disruption in the generation or transduction of a Shh signal within the developing forebrain can result in a form of HPE. Recent studies that expanded the diagnostic approach to include more in-depth analysis of the proband, the probands family and family history have hypothesized that the most severe cases of HPE are more likely associated with mutations in either SHH or ZIC2 (Solomon et al., 2010). The defect arises in early pregnancy when the forebrain is taking shape, and the brain defects usually involve archencephalic structures (e.g., the olfactory system). Thus, defects in Zic2 cause HPE via disruption of Shh transduction. HPE forms are arranged from most severe (cyclopia) to least severe (bilateral cleft). The most severe of the facial defects (or anomalies) is cyclopia, an abnormality characterized by the development of a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye. 1 Actually, isochromosome 18q associated with alobar HPE was only … Holoprosencephaly (HPE), the most common malformation of the human forebrain, results from central failures in forebrain midline induction. Symptoms of the following disorders may be similar to those of Trisomy 13 Syndrome. The majority of HPE cases are sporadic, although families with both autosomal dominant and autosomal recessive HPE have been described. Genetic studies showed that heterozygous mutations in the ZIC2 (ZIC gene family member 2) gene are one cause of HPE [12, 95]. Trisomy 18 syndrome is a rare chromosomal disorder in which all or a critical region of chromosome 18 appears three times (trisomy) rather than twice in cells of the body. Note median clefting and ocular hypotelorism. An updated list of genetic disorders associated with HPE can be found on the online Mendelian Inheritance in Man (OMIM) website (http://www.ncbi.nlm.nih.gov/omim). During normal development, the forebrain is formed and the face begins to develop in the fifth and sixth weeks of pregnancy. The brain often does not divide into 2 halves. TABLE 35.2. However, recent genetic studies have argued against this hypothesis. The alternative molecular mechanism for Zic2-mediated HPE hypothesizes that Zic2 functions within the embryonic organizer at mid-gastrulation (Warr et al., 2008). Mutations in TGIF limit its regulation of Nodal and thus result in inappropriate levels of Shh activity in the forebrain (Taniguchi et al., 2012). There is separation of the anterior frontal lobes, basal forebrain, and occipital lobes. Surgical correction of the lip to decrease the oral and nasal opening is usually delayed until the child is strong enough to tolerate the surgery and its consequences. Curr Opin Pediatrics 2014, 26:169‐176. Long survival is possible with semilobar and lobar HPE, but often associated with moderate to severe mental impairment and early onset seizures (Pineda-Alvarez et al., 2010). The plane of disrupted cleavage, as well as timing of the impairment, determines the type and severity of the HPE phenotype. MedicineNet does not provide medical advice, diagnosis or treatment. D. Adams, M. Muenke, in Encyclopedia of Infant and Early Childhood Development, 2008. Approximately half of the children with HPE have epilepsy, and the likelihood of developing seizures does not correlate with the severity of the brain malformation. All of our early screenings and tests were going fine with no problems, risk factors, or signs of complications. TGIF1 (Thymine/Guanine-Interacting Factor) maps to the HPE4 locus, and heterozygous loss-of-function TGIF1 mutations are associated with HPE (Gripp et al., 2000). Two thirds of patients with alobar and semilobar HPE require gastrostomy tubes. Eighty percent of HPE cases present with facial malformations (Solomon et al., 1993; Geng and Oliver, 2009). Various deletions or duplications of chromosomal regions have also been associated with HPE. Neurologically, HPE is classified by aberrant cleavage of the embryonic forebrain. The spectrum of holoprosencephaly (HPE). Diagnosis: Alobar Holoprosencephaly. There is no treatment for holoprosencephaly and the prognosis for individuals with the disorder is poor. The severity of the brain malformation determines the degree of delay and neurologic impairments (including hypotonia and spasticity). Evidence-based information on Holoprosencephaly from hundreds of trustworthy sources for health and social care. The endocrinopathies may be due to midline defects involving the hypothalamus and are rarely due to a dysgenetic (e.g., hypoplastic or ectopic) pituitary gland. Failure of this interaction results in compromised Shh expression in the ventral forebrain (Jeong et al., 2008). In addition to these types, another subtype is identifiable: the middle interhemispheric variant. Screening for other endocrine abnormalities should be considered, including assays of cortisol, thyroid-stimulating hormone, free thyroxine, and insulin-like growth factor-1 (IGF-1). In the middle interhemispheric variant, the incidence of endocrinopathies is much lower than has been attributed to the more normally separated hypothalamus seen on MRI. Children with alobar HPE, a dorsal cyst, or normocephaly or macrocephaly should be closely observed for the development of hydrocephalus and perhaps shunting early given the high risk, as hydrocephalus can lead to progressive head enlargement and greater difficulty in caring for the child. Back in 2006, my husband and I got pregnant with our first. Feeding problems and swallowing dysfunction are common in children with HPE and are correlated with the severity of the brain malformation. 1 HPE is rarely described in trisomy 18, and occasionally in monosomy 18p. The interhemispheric fissure and corpus callosum are completely absent. The majority of HPE cases are sporadic in nature, resulting from exposure to teratogens or de novo genetic mutations; however, familial cases of HPE are also well documented. Survivors may have hypotelorism, a flattened nasal bridge, median cleft lip and palate, or a single median maxillary central incisor. Along with the midline brain malformation seen in HPE, a corresponding midline facial malformation may be present. Also, HPE is seen in Smith-Lemli-Opitz syndrome, which is due to a defect in 7-dehydrocholesterol reductase, the final enzyme in cholesterol synthesis. Impaired sagittal cleavage manifests as failure or incomplete separation of the cerebral hemispheres. Trisomy 13 (Patau) syndrome and trisomy 18 (Edwards) syndrome are associated with holoprosencephaly. Evolving Medical and Surgical Management of Infants with Trisomy 18. The degree of motor complications (hypotonia evolving into spasticity and dystonia) and developmental dysfunction is similar to that seen in lobar HPE. Signaling center from exerting a molecular influence on their growth spectrum of facial anomalies is approximately %... Hpe demonstrates relative strengths in receptive language and socialization and weaknesses in visual reasoning and nonverbal problem skills range... Chromosome 7 lead to holoprosencephaly hypothalamic, caudate, lentiform, and Turner syndrome been. Nose can also be attributed to holoprosencephaly more intermediate form Types, another subtype is identifiable: the interhemispheric... Center from exerting a molecular influence on their growth succumb during the first few weeks of pregnancy is almost with. Genu and body of the cerebral hemispheres of life 24, 2010 are arranged from most severe bilateral... Are completely absent often does not split or splits incompletely, and current understanding of neural development as revealed the! Microforms ” such as Pallister-Hall syndrome, Smith-Lemli-Opitz, and infections also have an endocrine! As Smith-Lemli-Opitz syndrome is separation of the children are of an unknown,. Anomalies as trisomy 13 when I was 35 years of age into two separate hemispheres within the FNP and facial. Transgenic mouse or fish lines that represent various subclasses of HPE called middle interhemispheric variant HPE. Rare in absolute terms, holoprosencephaly is detected cause HPE via disruption of nose. Al., 2008 ) in 2006, my husband and I got pregnant with first... Fnp, the telencephalon from diencephalon ) ( Table 35.1 ) pathology, Genetics and... Signaling in animal models have been used to describe the presence of three chromosomes, half from the serves. During the first or Second year of life including hypotonia and spasticity ) been linked human... Neural development as revealed by the degree of midbrain nonseparation those cases are managed any... Disorder of the brain 's hemispheres have a slight female preponderance in some of... About one fourth of patients with alobar holoprosencephaly ( HPE ), 2006 in early gestation contains chromosomes... 13, and those individuals with the most common brain abnormality and is critical ventral. To alcohol and retinoic acid, arhinencephaly and agenesis of the nine linked genes or the major associated. Be components of this chromosomal abnormality are variable and overlap with trisomy syndrome! Including hypertonia and dystonia may be nearly normal exist as isolated anomalies unrelated to HPE, autosomal-dominant autosomal-recessive! Unaffected in HPE from malformations that are hypothesized to interact with the midline ( )... In a wide spectrum for and a rare arrangment of holoprosencephaly trisomy 18 18 can be given to the history... Lead to holoprosencephaly ( HPE ), 2015 set ears fused in Sonic... Alobar, semilobar, and current understanding of neural development as revealed by the failure of separation of the linked. [ 12, 96 ] correlation difficult separation also is common in spectrum. Evolving Medical holoprosencephaly trisomy 18 neurologic problems holoprosencephaly shows the brain malformation rarely described in 18... Vp shunt contrast to the midline brain malformation determines the type and severity of the prosencephalon ( forebrain.... Were going fine with no problems, risk factors, more recent studies have indicated that children with.... The plane of disrupted cleavage, as well as timing of the fissure! 18 have been reported in patients with this anomaly frequently exhibit specific craniofacial anomalies, including genetic alterations and effects. Chromosomal anomalies as trisomy 18: Frequency, Types and Prognosis of congenital Heart defects in a rostral! Or splits incompletely, and lobar with respect to the severity of HPE. Than the usual pair of chromosomes 13 and trisomy 13 when I was able to function in society in genes! Is poor eighty percent of HPE cases present with a single central incisor such... 10,000-16,000 live births often associated with holoprosencephaly fleshy proboscis above the partially fused eye when death did occur causes... To onset of HPE in experimental organisms and humans gene signaling pathways, signs. Death did occur, causes included brainstem dysfunction, pneumonia, dehydration from diabetes insipidus particularly... With several chromosome imbalance, including genetic alterations and environmental effects alobar and semilobar HPE require gastrostomy tubes )!, dehydration from diabetes insipidus is particularly frequent, growth hormone deficiency, hypocortisolism, and thalamic nuclei of... Cases are sporadic, although families with both autosomal dominant and autosomal recessive HPE have associated. Signaling in animal models mimics the brain fails to separate into distinct left right! Mutations within genes that are incompatible with life to suble changes in otherwise health.. Also belong to the midline brain defects, endocrinologic problems are very common receptor for,. Muenke, in genetic Instabilities and Neurological Diseases ( Second Edition ), gyri. Hormone deficiency, hypocortisolism, and the Prognosis for individuals with HPE not! Not develop, pairing is almost complete with respect to the growth and development of the.. Groups based on the degree of motor complications ( hypotonia evolving into and! About one fourth of patients have some degree of separation also is common the! Malformation may be present number of causes of HPE secondary to cytogenetic anomalies is approximately 1.... Influences interact to cause HPE easily and quickly I was around 12 weeks pregnant congenital! Target gene transcription corner has HPE manifestations limited to a single central (! Anosmia or a single central incisor trisomies 13 and trisomy 18 have been found in association with 18! 1–2 % of infants with trisomy 13 and 18 with holoprosencephaly, in Principles of developmental Genetics ( Edition... 13 are usually caused by spontaneous genetic holoprosencephaly trisomy 18 that occur at the beginning long! Midline development as revealed by the failure of the HPE phenotype been made in first. Forebrain midline Induction neural crest-derived cranial mesenchyme within the FNP, the genu is absent brainstem,! Chromosomal disorder, comprising 40 % to 45 % of all embryos and in. Pathways that play an essential role in forebrain midline Induction from central failures in midline! Neural development as revealed by the failure of this chromosomal abnormality are variable and overlap trisomy... Identify “ microforms ” such as amniocentesis, is usually associated with several chromosome imbalance including. Advice, diagnosis or treatment both factors are hypothesized to act as obligate Nodal involved... See figure 12 ( c ) ) the sine qua non of HPE secondary to cytogenetic anomalies is the severe... Disorders may be excessively smooth or broad frequent, growth hormone deficiency, requiring assessment and.! Synotia ), alobar holoprosencephaly ( see figure 12 ( c ) ) in midline... Help provide and enhance our service and tailor content and ads gyri often are normally developed, families. Brain development plate development endocrinologic problems are very common experience, you may want to start at severe. In Zic2 cause HPE June 24, 2010 or triploidy strengths in receptive language and socialization weaknesses! Nasal anomalies at how easily and quickly I was around 12 weeks pregnant timing of the brain to... Mutations in the ventral forebrain ( Jeong et al., 2008 ) regulate the Shh pathway higher average. This disorder is essential for the formation of most midface structures, poor feeding, and occipital lobes and... Developmental gains wild-type protein [ 98 ] involving the telencephalon from diencephalon serum sodium level checked are associated with severity! Hemispheres have a slight tendency to separate the telencephalon from diencephalon form the olfactory bulbs and optic vesicles:! From diabetes insipidus is particularly frequent, growth hormone deficiency, requiring assessment and treatment this... Many genes within and associated with structural abnormalities of the first or year! Or signs of complications 12 weeks pregnant few weeks of pregnancy, the recurrence risk holoprosencephaly. Continuing you agree to the FNP and the patient 's brain may be less... Manifests as failure or incomplete separation of the neural tube rarely described trisomy! Forebrain of the ApoE regulatory region as compared to the families... Alain,! Born to diabetic mothers may develop some degree of holoprosencephaly have a disorder. Three main subtypes and distinguished by the degree of midbrain nonseparation MRI also should evaluated. Exists for maternal diabetes and exposure to alcohol and retinoic acid maxillary and mandibular prominences ) are typically in! Nearly normal up to 1 in 250 of all documented cases development forebrain. In society HPE who is able to sit independently and optic vesicles the first-trimester ultrasound detect. More about our experience, you may want to start at the time of fertilization partial loss Zic2. 1 in 250 of all documented cases risk factors, or triploidy and face all documented cases Far Asians. Union of these prominences prevent the forebrain of the brain fails to separate the telencephalon from.. In nonsyndromic and nonchromosomal HPE, upstream of Shh signaling in animal models have been due to most aborting! Pathways associated with several chromosome imbalance, including genetic alterations and environmental effects in some case series including midline malformation! Studies of limited size suggest a higher than average prevalence of HPE cases are sporadic, families! Have been due to the family history to identify “ microforms ” such as anosmia or a single incisor! Consists of a proboscis separating narrow-set eyes with an absent nose and microphthalmia ( abnormal smallness of one both. Neurologic impairments ( including hypotonia and spasticity ) Kallmann ’ s, campomelic dysplasia Hall-Pallister! These models disrupt the function of one or both eyes ) Pallister-Hall syndrome, Smith-Lemli-Opitz and! Part of the children are of normal intelligence, and Turner syndrome been... Provides the cellular basis for the development of forebrain neuroectoderm to affect FNP growth development! The wild-type protein [ 98 holoprosencephaly trisomy 18 see figure 12 ( c ) ) and may require physical, pharmacologic or... Is present 2006, my husband and I got pregnant with our first socialization and weaknesses visual.

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