1 CLINICAL MANIFESTATIONS OF HEREDITY ANOMALIESBy: Mahdi Bijanzadeh MD, PhD.
2 Clinical manifestations of heredity anomaliesAt the end of this session, you should answer this questions: 1. What is disease vs. syndrome? 2. What is variance in expression? 3. Where “wide anterior fontanel” can be found? 4. What is low set ear? 5. What is underlying disorder of Simian crease?
3 A 4 years old boy has come with: - cleft lip - simian crease - flat nasal bridge What is your diagnosis?
4 Basis of approach Gather information: family history, physical examination. Non-specificity of individual defects: with rare exceptions, a clinical diagnosis of a malformation cannot be made on the basis of a single defect. Heterogeneity: similar phenotypes may result from different etiologies. Variance in expression: except for MR and small stature, it is unusual to find a given anomaly in 100% of patients with the same etiologic syndrome. Etiology: 50% no specific disorder, a small% structural chromosomal abnormality.
5 General terminology Disease: a condition of living body or of one of its parts that impairs normal functioning and is typically manifested by distinguishing signs and symptoms. Syndrome: a group of consistent and recognizable abnormalities, often with a known underlying cause. Non-syndromic disease: refers to disorder that appears without other abnormalities: deafness, MR., … Major anomaly: has an adverse outcome on function or social acceptability of the individual. Minor anomaly: neither medical nor cosmetic importance.
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7 Incidence Spontaneous first-trimester abortion: 50% of all human pregnancies before implantation. 15% before 12 w. Paterns: 80-85% with gross structural abnormalities % ch., submicros. or single gene abnormalities. Perinatal mortality: 28w. gestation-first week of life. 80% due to genetic factors: 1% recurrence risk. Newborn infants: 2-5% major and 10% minor anomalies. Major poor prognosis: 25% dying, 25% with mental or physical disability, 50% fair or good view after treatment. Childhood mortality: 1st year: 25%, 1-10y:20%, 10-15y: 7.5%
8 Morphogenesis: genetics & environmental factors: Dysmorphic syndrome, congenital abnormality, birth :defect Single abnormalities: Malformation Disruption Deformation Dysplasia Multiple abnormalities: Sequence Syndrome (Dysmorphology) Association: VATER
9 HEAD 1. Macrocephally 2. Microcephally 3. Wide Anterior Fontanel 4. Small Anterior Fontanel 5. Craniosynostosis 6. Torticollis 7. Frontal Bossing 8. Coarse face
11 Frequent & occasional in:Achondroplasia Hunter Syndrome Mucopolysaccharidosis Deletion 11q Syndrome Fragile X Syndrome Neurofibromatosis Syndrome, type I Osteogenesis Imperfecta Syndrome
12 Microcephalia Definition: circumference of head < two SD. smaller than average for person's age and sex. Usually because brain has not developed properly or has stopped growing.
13 Frequent & occasional in:Angelman Syndrome Bloom Syndrome Deletion 3p, 4p, 5p, 18p, 11q, 13q, 18q, 22q11.2 Syndromes Roberts-SC phocomelia Trisomy 13, 18 Syndromes X-linked -Thalassemia/Mental Retardation (ATR-X) S. Fanconi Pancytopenia Myotonic Dystrophy Syndrome Prader-Willi Syndrome Xeroderma pigmentosa Syndrome
14 Wide Anterior FontanelThe fontanelle allows skull to deform during birth to ease its passage through birth canal and for expansion of brain after birth. Definition: enlarged fontanelles are larger than expected soft spots for age of a baby.
15 Frequent & occasional in:Achondroplasia Congenital hypothyroidism Down syndrome Normal variation Familial macrocephaly Rickets Increased intracranial pressure
16 Small Anterior FontanelDefinition: Fontanel closure that occurs before three months of age.
18 Frequent & occasional in:*Idiopathic *hyperthyroidism, hypophosphatasia, rickets, or hyperparathyroidism. *More than 50 syndromes: Apert Syndrome Carpenter Syndrome Chondrodysplasia Punctata, X-linked Dominant type Deletion 11q, 13q Syndrome Duplication 3q Syndrome Williams Syndrome Abnormal brain development
20 Frequent & occasional in:- As part of overall clinical picture of Parkinson disease. - Congenital causes, such as pseudotumor of infancy, hypertrophy or absence of cervical musculature, spina bifida, hemivertebrae, and Arnold-Chiari syndrome. - Acquired: Otolaryngologic causes, Esophageal reflux, Syrinx with spinal cord tumor, Traumatic causes, Juvenile rheumatoid arthritis and …
22 Frequent & occasional in:- Acromegaly - Basal cell nevus syndrome - Congenital syphilis - Cleidocranial dysostosis - Crouzon syndrome - Hurler syndrome - Pfeiffer syndrome - Use of antiseizure drug: Trimethadione during pregnancy
23 Coarse face Definition: a constellation of facial features that includes: - large, bulging head - prominent scalp veins - "saddle-like, flat bridged with broad, fleshy tip“ nose - large lips and tongue - small, widely spaces and/or malformed teeth - hypertrophic alveolar ridges of gums
25 Frequent & occasional in:- Acromegaly - Coarse face- hypotonia- constipation - Congenital hypothyroidism - Some types of X-linked MR. - Some types of Mucopolysaccharidosis
34 Frequent & occasional in:Edwards Syndrome (Trisomy 18) 1q21 duplication Syndrome Basal Cell Nevus Syndrome DiGeorge Syndrome Loeys-Dietz Syndrome Apert Syndrome Craniofrontonasal dysplasia Neurofibromatosis Cri du chat Syndrome
38 Flat nasal bridge The nasal bridge: upper, bony part of the nose, overlying the nasal bones. A lower or higher than average nasal bridge can be a sign of various genetic disorders: A flat nasal bridge can be a sign of (Trisomy 21), Fragile X Syndrome, and/or Fetal Alcohol Syndrome. A widened nasal bridge can be seen with dystonia canthorum. dystopia canthorum, which is a lateral displacement of the inner canthi of the eyes.[1] Dystopia canthorum is associated withWaardenburg syndrome
40 Frequent & occasional in:- C syndrome - Often chromosomal deletion, trisomy, tetrasomy, duplication, partial duplication and monosomy. 1. 1q terminal deletion A rare chromosomal disorder where the terminal part of the long arm (q) of chromosome 1 is deleted resulting in various abnormalities....read more » 2. AIDS dysmorphic syndrome A rare syndrome involving craniofacial anomalies and developmental delay that occurs in infants infected with AIDS during the fetal stage....read more » 3. Acrocephalopolydactyly II A rare genetic disorder characterized by head, hand and genital anomalies as well as mental retardation....read more » 4. Acutane embryopathy A rare disorder caused by fetal exposure to retinoids and resulting in mental and physical birth defects....read more » 5. Bagatelle-Cassidy syndrome An extremely rare syndrome characterized by a large head, widely spaced eyes, hearing loss, short limbs and developmental delay....read more » 6. Brachytelephalangy, characteristic facies, Kallmann A very rare syndrome characterized primarily by very short end bones of fingers and facial anomalies....read more » 7. C Syndrome A rare inherited disorder characterized by a triangular-shaped head, facial anomalies, joint contractures and loose skin....read more » 8. Chromosome 1, 1p36 deletion syndrome A rare chromosomal disorder where deletion of a portion of chromosome 1 causes various abnormalities such as heart problems, mental retardation, developmental delay, facial dysmorphism and short stature. The symptoms are variable depending on the exact lo...read more » 9. Chromosome 12 trisomy A rare chromosomal disorder where there are three copies of chromosome 12 rather than the normal two resulting in various abnormalities....read more » 10. Chromosome 12, trisomy 12q A rare chromosomal disorder where there are three copies of the long arm (q) of chromosome 12 rather than the normal two resulting in various abnormalities. In most cases, death occurs during infancy. The type and severity of symptoms varies depending on ...read more » 11. Chromosome 12p deletion A rare chromosomal disorder where there is a deletion of the short arm (p) of chromosome 12 resulting in various abnormalities. The type and severity of symptoms varies depending on the amount and exact location of the genetic material that is deleted....read more » 12. Chromosome 12p deletion syndrome A rare chromosomal disorder where there is a deletion of the short arm (p) of chromosome 12 resulting in various abnormalities....read more » 13. Chromosome 12p tetrasomy syndrome A rare chromosomal disorder where there are four copies of the short arm (p) of chromosome 12 rather than the normal two resulting in various abnormalities....read more » 14. Chromosome 12q duplication syndrome A rare chromosomal disorder where there are three copies of the long arm (q) of chromosome 12 rather than the normal two resulting in various abnormalities. In most cases, death occurs during infancy....read more » 15. Chromosome 13 ring syndrome A rare chromosomal disorder where genetic material from one or both ends of chromosome 13 is missing and the two broken ends have rejoined to form a ring. The resulting type and severity of symptoms is determined by the amount and location of genetic mate...read more » 16. Chromosome 14q, partial deletion A rare chromosomal disorder involving deletion of genetic material from the long arm (q) of chromosome 14 resulting in various abnormalities....read more » 17. Chromosome 17 ring A rare chromosomal disorder where genetic material from one or both ends of chromosome 17 is missing and the two broken ends have rejoined to form a ring. The resulting type and severity of symptoms is determined by the amount and location of genetic mate...read more » 18. Chromosome 17q, partial duplication A rare chromosomal disorder involving an extra copy of genetic material from the long arm of chromosome 17. The type and severity of symptoms are determined by the amount and location of the duplicated genetic material....read more » 19. Chromosome 18q, partial deletion A rare chromosomal disorder involving deletion of genetic material from the long arm of chromosome 18. The type and severity of symptoms are determined by the amount and location of the lost genetic material....read more » 20. Chromosome 19q, partial duplication A rare chromosomal disorder where the long arm of chromosome is triplicated. The type and severity of symptoms is determined by the size of the duplicated genetic portion....read more » 21. Chromosome 1q duplication syndrome A rare chromosomal disorder involving duplication of the long arm (q) of chromosome 1 which results in various abnormalities depending on the size and location of the portion of duplicated genetic material....read more » 22. Chromosome 20p, partial duplication A rare chromosomal disorder where a copy of the short arm of chromosome 20 has been triplicated instead of duplicated resulting in various anomalies....read more » 23. Chromosome 21, tetrasomy 21q A rare chromosomal disorder where there is four copies of the long arm of chromosome 21 instead of the normal two which results in various physical and mental anomalies....read more » 24. Chromosome 22 monosomy syndrome A rare chromosomal disorder where there is only one copy of chromosome 22 in the body cells instead of two which results in various physical and mental abnormalities....read more » 25. Chromosome 22 trisomy mosaic A rare chromosomal disorder where three copies of chromosome 22 are present in some of the body's cells instead of the normal two. Severity of symptoms is determined by how many cells have the extra chromosomal material....read more » 26. Chromosome 22, monosome mosaic A very rare chromosomal disorder where one copy of chromosome 22 occurs in some of the body's cells and results in various anomalies. The type and severity of symptoms varies depending on the amount and exact location of the genetic material that is delet...read more » 27. Chromosome 22, monosomy mosaic A very rare chromosomal disorder where one copy of chromosome 22 occurs in some of the body's cells and results in various anomalies....read more » 28. Chromosome 22, trisomy A very rare disorder where there is an extra copy of chromosome 22 in all the body cells. The condition is usually fatal soon after birth or during the fetal stage....read more » 29. Chromosome 4, trisomy 4p A rare chromosomal disorder where a portion of chromosome four is duplicated so there is three copies of it instead of the normal two....read more » 30. Chromosome 5p duplication syndrome A rare chromosomal disorder where there are three copies of all or part of the short arm (p) of chromosome 5 rather than the normal two. The type and severity of symptoms is determined by the location and size of the genetic material duplicated....read more » 31. Chromosome 7p deletion syndrome A rare chromosomal disorder where part or all of the short arm (p) of chromosome 7 is deleted resulting in various abnormalities which are determined by the size of the deleted portion....read more » 32. Chromosome 8, monosomy 8q A rare chromosomal disorder involving deletion of the long arm (q) of chromosome 8 resulting in various abnormalities. The type and severity of symptoms varies depending on the amount and exact location of the genetic material that is deleted....read more » 33. Chromosome 8p duplication syndrome A rare chromosomal disorder where the short arm (p) of chromosome 8 is duplicated resulting in three copies instead of two. The type and severity of symptoms depends on the location and length of genetic material duplicated....read more » 34. Chromosome 9q deletion syndrome A rare chromosomal disorder where the long arm (q) of chromosome 9 is deleted resulting in variable symptoms....read more » 35. Coffin-Siris Syndrome A rare genetic disorder characterized by underdeveloped or absent fifth finger and toenails and coarse facial features....read more » 36. Dubowitz Syndrome A rare genetic and developmental disorder characterized by infantile eczema, small stature, microcephaly and peculiar facial features....read more » 37. Facial ectodermal dysplasia A very rare inherited disorder characterized by hair, teeth, nail and skin abnormalities. The type and severity of symptoms is variable....read more » 38. Fibrochondrogenesis A rare genetic disorder characterized by short stature, abnormal bone formation and stillbirth or neonatal death....read more » 39. Goldblatt-Viljoen syndrome A rare syndrome characterized by a fully or partially blocked nasal passage and abnormalities of the forearm bone (radius) and thumbs....read more » 40. Hypohidrotic Ectodermal Dysplasia An inherited disorder involving the developmental abnormalities during the fetal stage that can affect the skin, hair, nails, teeth and sweat glands. This form of ectodermal dysplasia is characterized by a reduced ability to sweat due to a lack of sweat g...read more » 41. Juberg-Marsidi syndrome A very rare inherited disorder characterized by severe mental retardation, delayed developmental milestones, muscle problems and growth retardation. The range and severity of symptoms is variable....read more » 42. Marshall syndrome A rare genetic disorder characterized by a distinctive face and vision and hearing impairment....read more » 43. Metaphyseal dysplasia Pyle type A rare genetic disorder characterized by bone deformities involving the limbs, skull and other parts of the skeleton....read more » 44. Metatrophic dysplasia A very rare form of dwarfism involving short limbs and a long trunk. Less than 100 cases of the condition have been reported....read more » 45. Opitz syndrome A rare genetic disorder characterized by wide-set eyes, hypospadias and swallowing difficulties....read more » 46. Pallister-Hall Syndrome A rare genetic disorder characterized by hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and polydactyly....read more » 47. Pierre-Robin syndrome with fetal chondrodysplasia A very rare inherited disorder involving bone growth abnormalities, impaired hearing and a characteristic face....read more » 48. Pseudodiastrophic dysplasia A rare genetic disorder characterized by short stature, contractures and joint dislocations....read more » 49. Simpson-Golabi-Behmel syndrome A rare genetic disorder characterized by accelerated growth and other defects....read more » 50. Tricho-hepato-enteric syndrome A very rare syndrome characterized mainly by hair and liver abnormalities as well as severe diarrhea that usually starts in early infancy and can lead to death....read more » 51. Type II Achondrogenesis-Hypochondrogenesis A rare genetic disorder characterized by very small stature, abnormal bone formation and early death
48 ANUS GENITALIA 1. Atresia 1. Hypogenitalism 2. Genital Ambiguity2. Displacement GENITALIA 1. Hypogenitalism 2. Genital Ambiguity 3. Virilization