Having in mind the fact that about 145 cases have been described in the literature so far, Dubowitz syndrome is a rare clinical entity with an unknown etiology [1] [2] [3]. Certain authors hypothesize that a genetic background (DNA ligase IV and RNA methyltransferase mutations), an autosomal recessive pattern of inheritance, and various hormonal abnormalities are involved in the pathogenesis [4] [5] [6]. Fortunately, the clinical presentation has been well-demarcated by several authors, and is composed of the following [1] [2] [3] [4] [5] [6]:

• Facial changes - One of the cardinal features of Dubowitz syndrome is a narrow and triangular-shaped face with micrognathia, a sloping forehead, and thin and sparse eyebrows and hair [1] [4]. Other common findings are low-set ears, wide-set eyes with drooping upper eyelids, a broad and wide nasal bridge, and facial asymmetry [1] [2] [3] [4]. Telecanthus, visual deficits, a cleft palate and several other facial deformities are less commonly encountered [1] [2] [3] [4].
• Growth abnormalities - In addition to a distinct facial appearance, a markedly reduced growth rate starting during intrauterine life is one of the main characteristics of Dubowitz syndrome [1] [2] [4] [5]. Virtually all individuals suffer from microcephaly, a short stature and a low body weight for appropriate age, whereas hypotonia (stemming from the weakness of the skeletal muscles) is also a frequent finding [1]. Furthermore, scoliosis, fused vertebrae, impaired rib development, toe fusion and feet-related problems (club foot, inverted foot, flat-footedness, etc.) are seen in a significant number of cases [1] [7].
• Psychiatric symptoms - Hyperactivity, aggressiveness, bedwetting, difficulties with sleep, and frequent withdrawal from other individuals or crowd (although rare) are often reported in Dubowitz syndrome [1] [3] [4]. A variable degree of mental retardation and learning impairment is observed as well [1] [3].

Other notable features are a high-pitched voice, gastrointestinal irritation (presenting as diarrhea), the presence of eczema, genital disorders (cryptorchidism, hypospadias, and underdevelopment of either male or female genitalia), frequent infections (most commonly of the ears, GI system, the lungs, the urinary tract and the sinuses), and several congenital heart diseases (atrial and ventricular septal defects, as well as patent ductus arteriosus) [1] [2] [3] [4]. Rare reports have described malignant tumors (primarily of hematologic origin), aplastic anemia and immunological deficits (IgA deficiency) [1] [3].

• Short Stature

  From Wikidata Jump to navigation Jump to search Human disease Dubowitz's syndrome (disorder) Dubowitz's syndrome Dwarfism-eczema-peculiar facies syndrome Intrauterine growth retardation, short stature, microcephaly, mild mental retardation with behavior [wikidata.org]

  To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. [ncbi.nlm.nih.gov]

  Abstract To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. [zora.uzh.ch]

• Recurrent Infection

  Eczema and recurrent infections require conservative treatment. Surgical intervention might be necessary for certain cardiovascular, urogenital, craniofacial or limb anomalies. Surveillance of hematological and malignant disorders is recommended. [orpha.net]

  She/he may be prone to recurrent infections, hypogammaglobulinemia, IgA deficiency, aplastic anemia, acute lymphatic leukemia, lymphoma, and/or neuroblastoma. contributor: Kelly A.Przylepa, revised 4/4/2003 creation date: John F. [dubowitzsyndrome.net]

• Multiple Congenital Anomalies

  The Dubowitz syndrome is a rare autosomal recessive multiple congenital anomaly/mental retardation syndrome. We report here a case of a young adult presenting with several features consistent with this diagnosis. [ncbi.nlm.nih.gov]

  congenital anomalies/dysmorphic syndrome-intellectual disability, malformation syndrome with short stature Named after Victor Dubowitz Authority control Q574741 Reasonator Scholia Statistics Media in category "Dubowitz syndrome" The following 2 files [commons.wikimedia.org]

  Winter and Michael Baraitser, A catalogue of multiple congenital anomaly syndromes, Multiple Congenital Anomalies, 10.1007/978-1-4899-3109-2_1, (1-672), (1991). [doi.org]

• Poor Feeding

  Dubowitz syndrome is a rare hereditary disorder whose main features are intra-uterine and post-natal growth retardation, characteristic facies, microcephaly, mental retardation and poor feeding. [ncbi.nlm.nih.gov]

  Abdominal/Gastrointestinal characteristics can include poor feeding, frequent vomiting, chronic diarrhea, and/or gastroesophageal reflux. In boys, there can be hypospadias, inguinal hernia, or cryptorchidism. [dubowitzsyndrome.net]

  Associations have been made with hyperactivity (4G" variable clefts of the soft palate (10% to 15%), poor feeding and gastroesophageal reflux (33%), chronic diarrhea (35%), and mild eczema (65%)7. [healio.com]

• High Pitched Voice

  Speech delays, an unusually soft, high-pitched voice, submucous cleft palate, and velopharyngeal insufficiency were noted in childhood. Mild mental retardation was present. [ncbi.nlm.nih.gov]

  Symptoms and Signs Symptoms largely vary among different patients, however other characteristics may include a soft but high pitched voice, webbing of fingers and toes but not totally, deformations of the palate, some abnormalities in the genitalia, eczema [medigest.uk]

  Other notable features are a high-pitched voice, gastrointestinal irritation (presenting as diarrhea), the presence of eczema, genital disorders (cryptorchidism, hypospadias, and underdevelopment of either male or female genitalia), frequent infections [symptoma.com]

  […] may be absent. congenital heart defects in 10%; other malformations: ocular, dental, skeletal, urogenital in male patients; frequent infections. mental retardation in 30-70 % of cases (from normal in 30% to severe retardation in 10%); siezures in 10%high-pitched [atlasgeneticsoncology.org]

• Failure to Thrive

  Failure to Thrive : growth failure, or failure to thrive (FTT), is a descriptive term and not a specific diagnosis. Although definitions vary, most use this term only when growth has been noted to be low or to have decreased over time. [ric.edu]

  Afterwards, the child is sometimes labeled as failure to thrive. The head is usually microcephalic and face is small with some elongation with age. [dubowitzsyndrome.net]

  The clinical features include short stature, failure to thrive, microencephaly, micrognathia, retrognathia, mild intellectual disabilities, and eczema. Synonym Intrauterine Dwarfism. [accessanesthesiology.mhmedical.com]

• Blepharoptosis

  Michels syndrome is noted by blepharophimosis, blepharoptosis, and epicanthus inversus plus a developmental defect of the anterior segment of the eye as well as skeletal defects in the form of spina bifida occulta, craniosynostosis, cranial asymmetry, [hindawi.com]

  Other physical problems caused by DS, such as blepharoptosis or cardiovascular defects, can be corrected through surgery [10]. [jmedicalcasereports.biomedcentral.com]

  E disease Pfeiffer Mayer syndrome Thumb deformity Multiple pterygium syndrome lethal type Dandy-Walker malformation with mental retardation, macrocephaly, myopia and brachytelephalangy Popliteal pterygium syndrome Lowry Wood syndrome Jeune syndrome Blepharoptosis [checkrare.com]

  Dysmorphic features included blepharoptosis, epicanthal folds, blue sclerae, small eyes, strabismus, broad nasal bridge, hypertelorism, high forehead, prominent chin, microstomia, high-arched palate, thin lips, short philtrum, bulbous nose, long neck, [fdna.health]

• Small Head

  Medical Term Other Names Description Microcephaly small cranium, Decreased circumference of cranium, Small head, Small skull, Small head circumference, Reduced head circumference, Decreased size of cranium, Decreased size of skull, Abnormally small skull [rarediseases.oscar.ncsu.edu]

  A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Definition Dubowitz syndrome is a genetic disorder defined by slow growth, a characteristic facial appearance, and a small head. [web.archive.org]

  MICROCEPHALY Infants born with Dubowitz syndrome have primary microcephaly, or a small head size at birth. [encyclopedia.com]

  Notably, some people with DS and FA have a small head size/microcephaly and a normal IQ, and/or a small head and normal development during infancy. A low IQ is far more common in DS than FA (~75% of DS patients compared to ~25% of DS patients). [forgottendiseases.org]

• Severe Short Stature

  Severe short stature as a result of intra-uterine growth retardation is one of the characteristics of Dubowitz syndrome. There have been few reports elaborating growth hormone secretory status in this syndrome. [ncbi.nlm.nih.gov]

  Search for more papers by this author First published: June 1996 Cited by: 3 Abstract Severe short stature as a result of intra‐uterine growth retardation is one of the characteristics of Dubowitz syndrome. [doi.org]

  Overall the best phenotypic match for Patient 3 is with the Carney Complex plus patient [43], who had few overt manifestations of Carney complex but had IUGR, feeding difficulties, global developmental delay (although not as severe), short stature (<1st [journals.plos.org]

• Eczema

  […] problems, eczema, and unusual and distinctive faci DUBOWITZ SYNDROME edit English Dubowitz syndrome Human disease Dubowitz's syndrome (disorder) Dubowitz's syndrome Dwarfism-eczema-peculiar facies syndrome Intrauterine growth retardation, short stature [wikidata.org]

  The phenotypic spectrum is quite variable and ranges from normal growth and head circumference with mild psychomotor retardation and lack of eczema to a condition of severe growth retardation, mental retardation, microcephaly, and eczema. [ncbi.nlm.nih.gov]

  I believe that this Handbook of Atopic Eczema Since atopic eczema first emerged as a disease entity in will not only enhance our ability to treat our patients, but the early decades of this century, it has been the subject will also stimulate our efforts [books.google.com]

• Skin Disease

  diseases, genetic dc.subject case report dc.subject developmental disorder dc.subject female dc.subject human dc.subject human tissue dc.subject monozygotic twins dc.subject preschool child dc.title SINDROME DE DUBOWITZ dc.type Artículos de revistas [repositorioslatinoamericanos.uchile.cl]

  Up to 1996, 141 cases were described worldwide.5 Dubowitz syndrome is characterised by mental and growth retardation (microcephaly, micrognathia),6 conspicuous behaviour (extreme shyness, hyperactivity) and skin diseases (eczema).7,8 The characteristic [journals.lww.com]

  disease Q80.9 ICD-10-CM Diagnosis Code Q80.9 Congenital ichthyosis, unspecified 2016 2017 2018 2019 2020 2021 2022 2023 Billable/Specific Code POA Exempt Allocheiria, allochiria R20.8 ICD-10-CM Diagnosis Code R20.8 Other disturbances of skin sensation [icd10data.com]

• Alopecia

  McPherson Clemens syndrome Malignant hyperthermia susceptibility type 3 Oslam syndrome L-arginine:glycine amidinotransferase deficiency Lin-Gettig syndrome Alopecia-intellectual disability syndrome Tabatznik syndrome Persistent Mullerian duct syndrome [checkrare.com]

  (hereditaria) (seborrheica) L65.9 ICD-10-CM Diagnosis Code L65.9 Nonscarring hair loss, unspecified 2016 2017 2018 2019 2020 2021 2022 2023 Billable/Specific Code Applicable To Alopecia NOS Alpers' disease G31.81 ICD-10-CM Diagnosis Code G31.81 Alpers [icd10data.com]

• Small Face

  For example, many people affected by the disease have a small face and head. Sometimes they have a high forehead that slopes as well. In many cases, the eyelids droop and the nose is wide and flat. [wisegeek.net]

  Craniofacial anomalies may include microcephaly (with head circumference below the third percentile), premature craniosynostosis, distinctive, small face with high forehead, flat supraorbital ridge, short palpebral fissures, scanty or absent lateral part [accessanesthesiology.mhmedical.com]

  Affected individuals have small face which is often triangular in shape with a pointed, receding chin. They also have broad wide-tipped nose, broad and sloping forehead, and wide-set eyes with drooping eyelids. [brighthub.com]

  […] retarded Short attention span Shyness Mental retardation mild to severe Stubbornness Short attention span Reduced muscle tone Small face Supraorbital ridge is swallow Head that is small Short palpebral fissures Tip of nose broad Flat nasal bridge Lateral [syndrome.org]

  […] jaw Small lower jaw [ more ] 0000347 Narrow face Decreased breadth of face Decreased width of face [ more ] 0000275 Postnatal growth retardation Growth delay as children 0008897 Protruding ear Prominent ear Prominent ears [ more ] 0000411 Ptosis Drooping [rarediseases.info.nih.gov]

• High Sloping Forehead

  Dubowitz syndrome (DS) (MIM#223370) (4) is a very rare genetic and developmental disorder involving multiple congenital anomalies including: 1) growth failure/short stature; 2) unusual but characteristic facial features; small triangular face, high sloping [ncbi.nlm.nih.gov]

  Other facial characteristics can include a shallow supraorbital ridge, asymmetry, micrognathia, dysmorphic features, and a high, sloping forehead. [dubowitzsyndrome.net]

  The typical findings of Dubowitz syndrome include growth failure/short stature, characteristic facial features such as a small triangular face, high sloping forehead, drooping eyelid (ptosis), short eyelids, increased distance between eyes (hypertelorism [rareguru.com]

• Short Attention Span

  Behavioral characteristics may include hyperactivity with short attention span, impulsivity and shyness. [orpha.net]

  attention span Shyness Mental retardation mild to severe Stubbornness Short attention span Reduced muscle tone Small face Supraorbital ridge is swallow Head that is small Short palpebral fissures Tip of nose broad Flat nasal bridge Lateral telecanthus [syndrome.org]

  Behavioral characteristics include hyperactivity, short attention span, and aggressiveness. Behavior problems include difficulty feeding, sleep disturbance, and bedwetting. [jocmr.org]

• Hyperactivity

  […] disorder Attention deficit Attention deficit disorder Attention deficit-hyperactivity disorder Attention deficits Childhood attention deficit/hyperactivity disorder [ more ] 0007018 Blepharophimosis Narrow opening between the eyelids 0000581 Clinodactyly [rarediseases.info.nih.gov]

  Characteristic behavior patterns which have not been cited previously are present in our cases; most patients are hyperactive, shy, hate crowds, and like music, rhythm, and vibrations from music speakers, tape recorders, or transmitted through floors. [ncbi.nlm.nih.gov]

In the absence of clear diagnostic criteria for Dubowitz syndrome and the striking similarity to several other disorders (including Fanconi anemia, fetal alcohol syndrome, Bloom's syndrome, Nijmegen breakage syndrome), the diagnosis might be difficult to make. With a properly obtained patient history and a meticulous physical examination, a presumptive diagnosis can be made [1] [4]. Exposure to significant amounts of alcohol during intrauterine life should be addressed during history taking, whereas a familial occurrence of the syndrome has been reported in a small number of cases, suggesting that a complete family history might also be of benefit [1] [2] [4]. The physical examination is, however, the pivotal step in the diagnostic workup, as the diagnosis relies on recognition of clinical features [3]. A comprehensive assessment of facial changes and growth rate, evaluation of cognitive skills, and determination of additional defects is crucial [1] [4]. Depending on the presence of additional signs and symptoms, appropriate diagnostic procedures should be employed. For example, echocardiography is needed in the setting of congenital heart diseases (CHDs), whereas a complete laboratory workup with an immunological profile in case frequent infections is noted, or if there is valid clinical suspicion toward a malignant disease.

• Delayed Bone Age

  Analysis of approximately 30 cases reveals prevalence of growth failure and delayed bone age, mild microcephaly, broad forehead with sparse frontal hair, telecanthus, blepharophimosis, abnormal pinnae, broad nose, and micrognathia. [ncbi.nlm.nih.gov]

  Skeletal issues can be delayed bone age, fifth finger clinodactyly, two/three toe syndactyly, and pes planus. Some are very prone to eczema or have severe allergies. There also can be sacral dimple (s), sparse scalp hair, and some hypotonia. [dubowitzsyndrome.net]

  Other common findings are behavioral disorders (hyperactivity, and/or autistic features), speech alterations, scanty or absent hair, foot abnormalities, delayed bone age, bone defects of the lower part of the spine (sacrum and coccyx), testicles that [rareguru.com]

  bone age. head: microcephaly; high forehead; sparse hair; broad nose; epicanthus; hypertelorism; blepharophimosis; microretrognathia. skin: eczema, a classical sign, may be absent. congenital heart defects in 10%; other malformations: ocular, dental, [atlasgeneticsoncology.org]

The pediatric dentist should possess the ability to recognize this rare alteration, to provide dental treatment and to refer for the necessary medical and multidisciplinary treatment. [ncbi.nlm.nih.gov]

Management and treatment Growth, dental speech, behavioral and intellectual development and a general health status check should be monitored regularly and treated appropriately. Eczema and recurrent infections require conservative treatment. [orpha.net]

Treatment of cardiospasm (achalasia of the esophagus in children). Surgery. 1961;50:731-735. Google Scholar | Medline | ISI 21. Yon J, Christensen J. An uncontrolled comparison of treatments for achalasia. Ann Surg. 1975;182:672-676. [journals.sagepub.com]

Treatment Like most genetic disorders, Dubowitz syndrome has no medical treatment but there are treatment options to lessen the severity of the symptoms. [brighthub.com]

Prognosis The prognosis is very variable depending on the severity and types of congenital anomalies present and the long-term outcome still remains elusive, as no data is available after puberty. [orpha.net]

Prognosis Concerning the prognosis for individuals with this syndrome it is very good providing that the managing of medical situations is continued. [syndrome.org]

Prognosis The prognosis of individuals affected with Dubowitz syndrome is good as long as the management of symptoms is maintained. They can survive to adulthood and lead fairly normal lives, although some of them have mild mental retardation. [brighthub.com]

Etiology The etiology of Dubowitz syndrome has not been evidently elucidated. Two causal genes have been put forward in separate isolated cases and include NSUN2 and LIG4. [orpha.net]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Elsevier Health Sciences, ١٨‏/٠٨‏/٢٠١٣ - 979 من الصفحات Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders [books.google.com]

Summary Epidemiology The total birth prevalence in Europe has been estimated at 1/500,000. Over 150 cases have been described to date. Clinical description Newborns often have a low birth weight with a small head and body size. [orpha.net]

Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province. Am J Public Health. 2000 Dec. 90(12):1905-12. [Medline]. May PA, Gossage JP, White-Country M, et al. [emedicine.medscape.com]

[…] study examined the specific oral features in one patient. [10] Another found abnormalities in the brain, such as corpus callosum dysgenesis, an underdeveloped anterior pituitary and a brain stalk with an ectopic (misplaced) posterior pituitary. [11] Epidemiology [en.wikipedia.org]

Pathophysiology The precise mechanisms leading to the very wide phenotypic presentations of the syndrome remain to be determined. Diagnosis No biochemical characterization to confirm Dubowitz Syndrome is available. [accessanesthesiology.mhmedical.com]

[…] and classification of disorders of sex development To make a diagnosis, it is essential not only to understand normal development but also to understand the different pathophysiological mechanisms responsible for DSDs. [patient.info]

Related Medscape Reference topics: Focal Muscular Atrophies Spinal Muscle Atrophy Spinal Muscular Atrophy Related Medscape resource: Resource Center Spinal Disorders Pathophysiology Spinal muscular atrophy (SMA) is caused by successive motor unit degeneration [emedicine.medscape.com]

How can Dubowitz Syndrome be Prevented? Currently, Dubowitz Syndrome may not be preventable, since it is a genetic disorder. [dovemed.com]

Mutations in the DHCR7 gene reduce or eliminate the activity of this enzyme, preventing cells from producing sufficient cholesterol [23, 24]. [jmedicalcasereports.biomedcentral.com]

Am J Med Genet C Semin Med Genet ^ a b Microcephaly Information Page at NINDS ^ "Microcephaly – Symptoms, Treatment and Prevention". The HealthCentralNetwork. Archived from the original on 2007-05-13. [en.wikipedia.org]

1. Huber RS, Houlihan D, Filter K. Dubowitz Syndrome: A Review and Implications for Cognitive, Behavioral, and Psychological Features. J Clin Med Res. 2011;3(4):147-155.
2. Lee MK, Lee YS. Anesthesia of a patient with Dubowitz syndrome -A case report-. Korean J Anesthesiol. 2010;58(5):495-499.
3. Turkbeyler IH, Pehlivan Y, Comez G, et al. Esophagus cancer and IgA deficiency in a patient with Dubowitz syndrome: a case report. Tokai J Exp Clin Med. 2011;36(2):29-30.
4. Chehade C, Awwad J, Yazbeck N, et al. Dubowitz syndrome: common findings and peculiar urine odor. Appl Clin Genet. 2013;6:87-90.
5. Yue J, Lu H, Lan S, et al. Identification of the DNA Repair Defects in a Case of Dubowitz Syndrome. Borgmann K, ed. PLoS One. 2013;8(1):e54389.
6. Martinez F, Lee JH, Lee JE, et al. Whole Exome Sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012;49(6):380-385.
7. Ballini A, Cantore S, Tullo D, Desiate A. Dental and craniofacial characteristics in a patient with Dubowitz syndrome: a case report. J Med Case Reports. 2011;5:38.