This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of isolated dysmorphic features

Cole, Sarah

Taylor, Matthew

English

University of Missouri: MOspace

Isolated Dysmorphologies         Page 1 of 8    7.7.10 Dysmorphic Features: Isolated Dysmorphologies Background 1. Dysmorphic features  o Abnormal body variations that can be measured or characterized (congenital anomalies or birth defects')  Singular anomalies often diagnostically insignificant, but multiples can aid the dx of a larger synd  Epidemiology of dysmorphology  o Incidence of major malformations is approximately 2-3% of live births o Congenital malformations account for approximately 20% of infant deaths  o This summary is limited to dysmorphic features that may be found on physical exam   Pathophysiology 1. Etiology is diverse but may include genetic, infectious, chemical or metabolic causes  o Physical causes may include decreased amniotic fluid, compression, torsion 2. Different organ systems are susceptible to teratogenesis during different stages of development  o Most major malformations occur in the embryonic period (3 to 8 weeks) o Functional defects and minor malformations may occur throughout the fetal period (9-38 weeks)   CNS, sensory organs, teeth, and external genitalia remain susceptible  Diagnosis 1. Abnormalities of the head and face  o Size - etiology of macro / microcephaly is diverse and poorly understood   Macrocephaly - Occipitofrontal circumference above 98th percentile for age. Often associated with megalencpaly  Microcephaly - Occipitofrontal circumference 2 SD below mean for age 2. Abnormalities of the skull and facial bones  o Craniosynostosis - Premature fusion of one or more cranial sutures   Appears on physical examination as abnormal head shape   Dolichocephaly: premature sagittal suture closure; long skull with a prominent forehead and occiput; approximately 1.9 per 10,000 births  Brachycephaly: premature coronal suture closure; short skull with a high, wide forehead; approximately 0.8 per 10,000 births  Trigonocephaly: premature metopic suture closure; triangle-shaped skull; approximately 0.67 per 10,000 births  Craniosynostosis is an indication for referral to a neurosurgeon to prevent neurologic complications o Micrognathia - a reduction in size in part or all of the mandible   Relatively common (approximately 1 in 100 newborns) Isolated Dysmorphologies         Page 2 of 8    7.7.10  Often part of a multiple congenital anomaly syndrome; can also be familial, teratogenic, or mechanical (e.g. in olygohydramnios sequence)  o Malar hyploplasia - characteristic of Treacher-Collins syndrome 3. Abnormalities of the ear  o Size: Microtia is characteristic of trisomy 21  o Protrusion: may be secondary to compression / injury, hypotonia, collagen defects, turner syndrome o Auricular tags ("ear tags"): anomalous nodules or protrusions, usually anterior to the ear   Common (approximately 1% of newborns), usually isolated (approximately 95% of cases)  If no other obvious defect present, and family history negative, not significant o Auricular pits: depressions, dimples, or fossae antr or slightly superior to the ear   Common (approximately 1% of newborns), not significant  o Abnormalities of the ear (including abnormal position, rotation, or shape) assoc w/ renal anomalies 4. Abnormalities of the eye  o Coloboma (absent tissue in the eye - iris)   Isolated (primary ocular defect), including familial  Syndromic, most commonly CHARGE syndrome (coloboma, heart defects, atresia of the nasal choanae, retardation of growth / development, genitourinary anomalies, ear abnormalities)   W/o a postive family history for isolated coloboma, echocardiography and renal ultrasound are indicated o Cataracts (incidence 2 / 10,000 births)   Isolated (most common, 50-60% of cases)   Hereditary (most commonly autosomal dominant), sporadic / idiopathic  Galactosemia / galactokinase deficiency (sole clinical manifestation)  With other defects   With ocular defects  Ocular disorders (e.g. anirida, micropthalmia)  With other non-ocular congenital anomalies  Chromosomal disorders (trisomies 13, 18, 21; XO syndrome)  Intrauterine infections (esp. TORCHES)  Metabolic disorders (e.g. Zellweger, galactosemia, Smith-Lemli-Opitz)  Chromosomal analysis and genetic testing are indicated o Red reflex   Test should be performed in a darkened room, from a distance of 18 inches   Potential causes for an abnormal red reflex  o Cataracts o Foreign bodies Isolated Dysmorphologies         Page 3 of 8    7.7.10 o Opacities o Iris abnormalities o Retinal abnormalities (including tumors, e.g. retinoblastoma  Dark spots, asymmetry, markedly diminished reflex, or a white reflex are all indications for referral to an ophthalmologist  Pos family hx for retinoblastoma; congenital, infantile, or juvenile cataracts; or retinal abnors should be referred to an ophthalmologist for a complete eye examination, regardless of the findings of the red reflex test o Inner canthal fold, Brushfield spots (white / gray spots on iris): characteristic of Trisomy 21 5. Abnormalities of the mouth and palate  o Cleft lip and/or palate   Assoc w/ many syndromes; sometimes isolated  In combination w/ other malformations, chromosomal analysis indicated o Micrognathia   Oculo-auriculo-vertebral spectrum disorders (with other craniofacial findings)  Treacher Collins syndrome (with malar hypoplasia)  Robin sequence (with cleft palate)   Teratogens (including radiation and drugs)  o Facial asymmetry   Asymmetric facies at rest   Absence / hypoplasia of facial bones, soft tissue  Oculo-auriculo-vertebral spectrum disorders (see above, with micrognathia)  Asymmetric crying facies   Absence / hypoplasia of depressor anguli oris muscle; may be associated with other malformations  6. Abnormalities of the nose  o Arhinia (partial or complete absence of nose), bifid nose, polyrrhinia, and nostril coloboma: all sporadic and very rare o Choanal atresia   Presumptively diagnosed by the inability to pass a rubber catheter more than 32 mm into the nose   Associated anomalies, including CHARGE syndrome and Treacher Collins syndrome, occur in 50% of cases o Proboscis (blind-ended, tubelike structure)   Holoprosencephalic proboscis is the m/c form, w/ a poor prognosis  Other forms (lateral nasal, supernumerary, and disruptive probosci) are rare  7. Abnormalities of the neck  o Webbing   Characteristic of Turner syndrome and Noonan syndrome   Isolated Dysmorphologies         Page 4 of 8    7.7.10 o Neck masses   Congenital, developmental, neoplastic, or inflammatory   In children, inflammatory > congenital / developmental > neoplastic   80% of neck masses in children are benign   Anterior triangle masses   Thyroglossal duct cyst (m/c, behind adenopathy)  o Midline, painless, moves with swallowing, elevates with tongue protrusion  Dermoid cyst (teratoma)  o Midline, most commonly submental, does not move w/ swallowing or elevate with tongue protrusion; distinguish from thyroglossal duct cyst o May become secondarily infected and painful  Thyroid mass (thyrotoxicosis, thymoma)  Sialadenitis  o Exquisitely tender; may be secondary to dehydration, poor hygiene, obstruction  Branchial cyst  o Common, anterior to SCM; may become secondarily infected; can cause abscess  Posterior triangle masses   Lipoma  Vascular / lymphatic malformation  Masses in either triangle  o Lymphadenitis (most common) o Infantile hemangioma  o M/c congenital malformations o Appear at or after birth; rapid proliferation from 6 to 18 months followed by slow involution over 6 to 8 years  Rhabdomyosarcoma  o Common; painless, expanding mass, may cause obstruction o Neuroblastoma o Lymphoma o Abscess  Masses in the sternocleidomastoid  o Fibromatosis coli  o Diffuse muscular swelling; presents as torticollisis 8. Abnormalities of the limbs  o Polydactyly   Use the following terminology:   Preaxial: involving the radial side of the limb  o Duplication of a normal biphalangeal thumb (type I) o Opposable thumb w/ three phalanges (type II) o Duplication of the index finger, w/ or w/o a thumb (type III) Isolated Dysmorphologies         Page 5 of 8    7.7.10  Postaxial: polydactyly on the ulnar or fibular side of the limb  Central: duplication of the second, third or fourth digit  Often occur simultaneously w/ syndactyly o Syndactyly: failed separation of the digits   May be cutaneous (involving soft tissue) or osseous (involving the bones)  Often occur w/ polydactyly, brachydactyly, or camptodactyly o Limb deficiencies   Use the following terminology:   Total (amelia) or partial (meromelia) absence of limb  Terminal (all segments beyond a point involved) or intercalary (proximal segment involved w/ at least part of distal segment present)  Transverse (extending across the width of the limb) or longitudinal (extending along the length of the limb)  Upper or lower limb; right or left side  Bones involved; portion of bone deficient (proximal, middle, distal)   Etiology may include:   Genetic causes (30% of cases)  Vascular disruptions (35% of cases)  Teratogens, including maternal diabetes, thalidomide, warfarin, cocaine (4% of cases)  Unknown cause (32% of cases)  o Constriction rings: distinctive soft tissue depressions encircling a limb (esp. the digits but also the limbs, neck, trunk, or head)   May involve a single limb, more commonly involves multiple limbs; associated w/ other deformations, including amputations, skin defects, syndactyly, and club-foot  Incidence approximately 1 per 10,000 live births; low recurrence risk 9. Genitourinary abnormalities  o Male   Cryptorchidism: failure of one or both testes to descend   Common, esp. w/ lower birth weights   3-4% of male infants w/ BW >2500 grams, 21-23% of male infants with BW <2500 grams; incidence falls to 0.8% at 3 months  Normal in the preterm male; examination should be repeated at intervals postnatally  Dx at birth or later, based on palpation of the scrotum  To exclude retractile testis, examine in various positions or in a warm bath  Isolated, or may be related to various male pseudohermaphroditic syndromes  Treatment should involve first hormonal stimulation, followed if necessary by surgical release of the testes (orchidopexy) to improve fertility and reduce cancer risk Isolated Dysmorphologies         Page 6 of 8    7.7.10  Inguinal hernia: hernation of the abdominal contents into the inguinal canal   Direct (medial to the inferior epigastric artery) or indirect (lateral to the artery)  Common (incidence of 20 to 30 per 1000 male live births)  o Occurs occasionally in females (3 to 4 per 1000 female live births) o Esp. preterm infants o Recurrence risk for siblings is high (approximately 30%)  Usu. isolated; may be associated with Marfan, Ehler-Danlos or cutis-laxa sydromes  Risk of incarceration of hernial contents higher in infants than children or adults  Repair involves replacement of abdominal contents into the abdomen and ligation of the hernial sac  Male pseudohermaphroditism: abnormalities of external genitalia that preclude determination of genetic sex from physical examination alone   Of greatest concern to the family physician and the parent is deciding the sex of rearing  Hypospadias: displacement of the urethral meatus from the tip to the ventral surface of the penis   Common (approximately 4 in 1000 male births)  Dx may be made at birth based on visual inspection, or later in life based on deviation of the urinary stream  Usu. isolated; may be part of a syndrome; urogenital anomalies especially assoc. w/ more severe (I.e., proximal) forms of hypospadia  Should be distinguished from congenital adrenal hyperplasia (enlarged clitorus) by the presence of testes o Female   Vaginal atresia: absence of the lower third of the vagina, w/ normal external vagina, cervix, and uterus   Occurs in approximately 1 in 40,000 female births  Most cases of "absent vagina" are Müllerian aplasia (below); only about 10% are isolated vaginal atresia  Presents as amenorrhea, often endometriosis secondary to retrograde menstruation through the uterine tubes   Usu. occurs as an isolated anomaly, but may also occur as a component of a major malformation syndrome  Tx requires surgical creation of a neovagina  Müllerian aplasia: absence of vagina, uterus, uterine tubes, and cervix   Occurs in approximately 1 in 4000 to 5000 female births  Rarely diagnosed before puberty; more commonly pts present with amenorrhea (but otherwise normal sex characteristics) Isolated Dysmorphologies         Page 7 of 8    7.7.10  Associated urinary tract anomalies (e.g. ectopic kidney, renal agenesis, etc.) and skeletal abnormalities common  Clitoromegaly: isolated hypertrophy of the clitorus (w/o other signs of masculinization)   Dx at birth; may be isolated, related to an endocrine disorder, or related to a multisystem disorder  May complicate determination of sex; palpation of testes to distinguish from a normal penis  Tx involves correction of the etiologic factor and possibly surgical correction  Ambiguous genitalia: external genitalia that display both male and female characteristics   Causes include:  o Chromosomal aneuploidies o Deficiencies in adrenal steroid synthesis (e.g. congenital adrenal hypoplasia) o Multiple anomaly syndromes   Requires consultation with specialists in genetics, urology, endocrinology, and family counseling   Sex of rearing is of primary importance  Hermaphroditism: presence of both ovarian and testicular tissues   Patient may be 46,XX (approximately 60% of cases), 46,XY (approximately 7% of cases), or mosaic (approximately 33% of cases)  Must exclude male and female pseudohermaphroditism  Of greatest concern to the family physician and parent is deciding the sex of rearing 10. Miscellaneous abnormalities  o Anal / rectal atresia   Relatively common (approximately 1 in 2500 births)  Detected at birth or soon after, based on visual inspection or failure to pass meconium  Associated with genitourinary malformations (e.g. rectourethral fistula, renal malformations), various other malformations (gut atresias, vertebral anomalies, etc.)  o Spina bifida   Myelomeningocele or meningocele   Readily diagnosed prenatally or at birth based on the presence of the lesion on an infant's back  Spina bifida occulta   Less readily visible; diagnostic signs include neurological impairment below the lesion, and cutaneous markers on the surface of the lesion, including a tuft of hair ("faun's beard"), hemangioma, or lipoma  Spina bifida is also associated with cardiac, anal, renal, abdominal wall, facial, and ophthalmic defects  Suspicion of spina bifida should be investigated via CT or MR  Isolated Dysmorphologies         Page 8 of 8    7.7.10   References 1. Kumar, Praveen & Burton, Barbara K. Congenital malformations: evidence-based evaluation and management. (2008). New York: McGraw Hill Medical. 3-4.  2. Stevenson, Roger E. & Hall, Judith G. Human malformations and related anomalies (2nd edition). (2006.) Oxford: Oxford University Press. 221-234, 288-289. 3. Bodhurtha, Joann. (1999). Assessment of the newborn with dysmorphic features. Neonatal Network 18(2); 28. 4. Hunter, A. G. W., & Yotzuyanagi, T. (2005). The external ear: more attention to detail may aid syndrome diagnosis and contribute answers to embryological questions. American Journal of Medical Genetics 135A; 241-242. 5. Stevenson, Roger E. & Hall, Judith G. Human malformations and related anomalies (2nd edition). (2006.) Oxford: Oxford University Press. 351-354. 6. Kumar &c. 113, 122-129. 7. Kliegman, Robert M., Behrman, Richard E., Jenson, Hal B. & Stanton, Bonita F. Nelson Textbook of Pediatrics (18th edition). (2007.) Philadelphia: Saunders Elsevier. Chapter 627. 8. (2008). Policy statement: Red reflex examination in neonates, infants, and children. Pediatrics 122; 1401-1404. 9. Kumar &c. 97, 101-103. 10. Stevenson &c. 288. 11. Kumar &c. 105-107. 12. Stevenson &c. 374-379. 13. Cummings, Charles. Cummings: Otolaryngology: Head & Neck Surgery, 4th Ed. (2005.) Mosby: Philadelphia, Pennsylvania. Chapter 112. 14. Marx, John A. Marx: Rosen's Emergency Medicine, 7th Ed. (2009.) Mosby: Philadelphia, Pennsylvania. Chapter 70. 15. Turkington, J R A, Paterson, A, Sweeney, L E, & Thornbury, G D. (2005). Pictorial review: neck masses in children. The British Journal of Radiology 78; 75-84. 16. Rakel, Robert E. Rakel: Textbook of Family Medicine, 7th ed. (2007.) Saunders: Philadelphia, Pennsylvania. Chapter 25, subsection: "The Neck". 17. Rosa PA, Hirsch DL, Dierks EJ. (2008.) Congenital neck masses. Oral and Maxillofacial Surgery Clinics of North America 20: 342. 18. Adam, Andy and Dixon, Adrian K. Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging (5th ed.). (2008.) Elsevier: Philadelphia, Pennsylvania. Chapter 45, subsection: "Fibrous tumors." 19. Stevenson &c. 937-966, 840. 20. McGuirk, CK, Westgate, MN, & Holmes, LB. (2001). Limb deficiencies in newborn infants. Pediatrics 108.4.e64; 1-2. 21. Stevenson &c. 871-874, 1116-1120, 1258-1302. 22. Kumar &c. 44-45.   Authors:  Matthew Taylor, DO, & Sarah Cole, DO, St. Louis University FMRP  Editor:  Kara Cadwallader, MD, Rural FMR of Idaho 

Dysmorphic features: isolated dysmorphologies

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Dysmorphic features: isolated dysmorphologies

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