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Fetal Alcohol Spectrum Disorders: Guidance for Recognition, Diagnosis, Differential Diagnosis and Referral Yasmin Senturias, MD, FAAP,a,b,c and Alexander Asamoah, MD, PhDd
etal alcohol syndrome (FAS) is defined by specific diagnostic criteria as delineated by the National Center on Birth Defects and Developmental Disabilities (NCBDD), Centers for Disease Control and Prevention (CDC), and the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect1 (Table 1)1 (Fig 1).2 It is one of the most common causes of developmental and intellectual disabilities in the US, occurring in 0.2–1.5/1000 births in the United States.3 Symptoms can range in severity but usually include a combination of physical, neurological, behavior, and learning problems. Children with the characteristic facial features, growth deficits, and central nervous system (CNS) abnormalities meet the criteria for FAS with or without documented prenatal alcohol exposure. For other disorders in the spectrum, as originally outlined by the Institute of Medicine (IOM), the full facial, growth, and CNS criteria for FAS may not be met but there must be confirmation of prenatal alcohol exposure. This is a narrow set of criteria that can miss many patients who have neurocognitive effects from alcohol exposure but do not have the classic triad essential for the diagnosis of FAS. In fact, research has shown that children who were exposed to alcohol in utero but do not meet the criteria for FAS have similar cognitive and behavioral characteristics.4
F
From the aDevelopmental-Behavioral Pediatrics Program, Levine Children's Hospital, Charlotte, NC; bDevelopmental and Behavioral Pediatrics of the Carolinas-Charlotte, Carolinas Healthcare System, Charlotte, NC; c Department of Pediatrics, University of North Carolina, Charlotte, NC; and dUniversity of Louisville, Louisville, KY. Curr Probl Pediatr Adolesc Health Care 2014;44:88-95 1538-5442/$ - see front matter & 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.cppeds.2013.12.008
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Other disorders on the spectrum include AlcoholRelated Neurodevelopmental Disorder (ARND), Partial FAS (PFAS), and Alcohol-Related Birth Defects (ARBD). Using the revised Institute of Medicine Criteria set forth by Hoyme et al.,5 ARND can be diagnosed in children with normal growth and structural development and who have characteristic cognitive or neurobehavioral abnormalities that are typical of prenatal alcohol exposure, including problems in executive functioning, communication, emotional lability, motor dysfunction, poor academic performance, deficits in social interactions, and unusual physiologic responses (including problems in sleep and hyperresponsiveness to sensory stimuli). Neurodevelopmental Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) is the new terminology that has been proposed in the Diagnostic and Statistical Manual (DSM) V, and the criteria for the ND-PAE diagnosis is listed in the appendix of DSM-V. The proposed criteria includes that the patient was “exposed to alcohol at any time during gestation, including prior to pregnancy recognition and the exposure level was more than minimal”6 along with presence of neurocognitive impairment, impairment in self-regulation, and impairment in adaptive functioning. Minimal intake means “no more than 1–13 drinks per month and no more than 2 drinks per occasion.”6 Neurocognitive impairments in ND-PAE include global intellectual impairment, impairment in executive functioning, impairment in learning, impairment in memory, and impairment in visual–spatial reasoning. Impairment in self-regulation includes impairment in mood or behavioral regulation, attention deficit, and impairment in impulse control. Deficits in adaptive functioning include communication deficit, social impairment, impairment in daily living, and motor impairment.6,7 PFAS is diagnosed in the presence of facial
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TABLE 1. The criteria for FAS diagnosis1
A. Requires all three of the following findings: 1. Documentation of all three facial abnormalities (smooth philtrum, thin vermillion, and small palpebral fissures). 2. Documentation of growth deficits. 3. Documentation of CNS abnormality. B. Facial dysmorphia. Based on racial norms, individual exhibits all three characteristic facial features: 1. Smooth philtrum (the University of Washington Lip–Philtrum Guide rank 4 or 5). 2. Thin vermillion border (the University of Washington Lip–Philtrum Guide rank 4 or 5). 3. Small palpebral fissures (at or below the 10th percentile). C. Growth problems. Confirmed prenatal or postnatal height, or weight, or both, at or below the 10th percentile, documented at any one point in time (adjusted for age, sex, gestational age, and race or ethnicity). D. Central nervous system abnormalities Structural Head circumference (OFC) at or below the 10th percentile adjusted for age and sex. Clinically significant brain abnormalities observable through imaging. Neurological Neurological problems not due to a postnatal insult or fever or other soft neurological signs outside normal limits. Functional Performance substantially below that expected for an individual's age, schooling, or circumstances, as evidenced by the following: 1. Global cognitive or intellectual deficits representing multiple domains of deficit (or significant developmental delay in younger children) with performance below the 3rd percentile (2 standard deviations below the mean for standardized testing). OR 2. Functional deficits below the 16th percentile (1 standard deviation below the mean for standardized testing) in at least three of the following domains: Cognitive or developmental deficits or discrepancies. Executive functioning deficits. Motor functioning delays. Problems with attention or hyperactivity. Poor social skills. Other (e.g., sensory problems, pragmatic language problems, or memory deficits). E. Maternal alcohol exposure 1. Confirmed prenatal alcohol exposure. 2. Unknown prenatal alcohol exposure.
characteristics that meet the criteria for FAS and abnormalities in either in growth or in the CNS domain.5 ARBDs are diagnosed when there is confirmed exposure to alcohol in utero, normal growth, the typical facial characteristics, and specific structural abnormalities (either major malformations or a pattern of minor
malformations).5 It is now known that relying on facial features for the identification of children with FASDs largely underidentifies the population of all alcoholexposed pregnancies as the vast majority of individuals exposed to alcohol during pregnancy do not present with the FAS facial phenotype but rather with the CNS
Fig 1. Examples of the FAS facial phenotype (small eyes, smooth philtrum, and thin upper lip) across three races: (A) Caucasian, (B) Native American, (C) African American. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.9
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effects.8 Of all the conditions in the spectrum, ARND (more currently referenced as ND-PAE) is estimated to be 10 times more common than FAS.3
The Facial and the Growth Criteria in FAS The facial and the growth criteria are quite straightforward, but in order to evaluate the facial criteria, it is helpful to use the following: a clear plastic ruler with blunt edges and the University of Washington Lip– Philtrum guides (Fig 2).9 The Lip–Philtrum Guide (www.fasdpn.org)10 is a 5-point pictorial scale that measures the smoothness of the philtrum and the thinness of the upper lip. A rank of “1” on the scale depicts a deeply grooved philtrum and a thick upper lip; a rank of “5” depicts a smooth philtrum and thin upper lip that is characteristic of a child with FAS. There are two lip– philtrum guides. Guide 1 is used for Caucasians and all other races with lips similar to Caucasians. Guide 2 is used for African-American and all other races with lips as full as African-Americans. FAS facial features require a Rank 4 or Rank 5 lip and philtrum (Fig 2).9 Palpebral fissure length is measured using a clear plastic ruler from the inner to outer corners of the eye (the endocanthion to the exocanthion) (Fig 3)9 and then the measurement is compared to a nomogram or plotted in an excel file using the following link: http://depts.washington.edu/fasdpn/ pdfs/astley-pfl-zscore-calculator.xls11; these would account for variations due to age. Further training on the diagnosis of facial criteria can be obtained by accessing the American Academy of Pediatrics FASD Pedialink at aap.org/fasd12 or the 4-Digit Diagnostic Code of the University of Washington.9 As defined in the 2004 NCBDD-CDC National Task Force guidelines, the growth criteria requires the usual height and weight measures and is positive when there is confirmed prenatal or postnatal height, weight, or both at or below the 10th percentile documented at any point in time and adjusted for age, sex, gestational age, race, ethnicity, and even nutritional or genetic factors, when applicable.
The CNS Criteria for FAS The CNS criteria for FAS can be met by documenting structural, neurological, or functional abnormality in FAS. The structural criteria are met either when there is a small head size (head size at or below the 10th percentile) or when there are structural
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abnormalities seen on imaging. Neurological abnormalities can be seen on exam and can consist of either focal findings (such as tremor) or unprovoked seizures. The CNS functional abnormalities are often best gauged by how the child thinks, learns, and behaves, as well as by reviewing information obtained from neuropsychological or developmental testing. Examples of CNS abnormalities are seen in Table 2.1 In infancy, the CNS dysfunction may be characterized by poor suck and irritability. These infants may benefit from nutritional support and from decreasing environmental overstimulation. Toddlers with an FASD may appear to be very busy and distractible and may have problems with balance and coordination. They may also have difficulties in sleep and in managing sensory stimuli, and these items need to be noted by clinicians. Difficulties in sleep and in managing sensory stimuli may be manageable by guidance in the medical home but referrals to a sleep clinic and to an occupational therapy, respectively, may also be necessary. The toddler's difficulties with comprehension and problem solving may result in prolonged tantrums. This problem becomes more evident in the preschool years when children are expected to have more self-regulation abilities. In fact, poor “self-soothing” appears to be one of the most common presenting symptoms of an alcohol-related neurodevelopmental disorder.13 Although early expressive language milestones may be normal, comprehension and understanding of concepts may lag behind and require language therapy. Furthermore, causeand-effect reasoning is less efficient for children with FASDs, making it more difficult for them to learn from past experience. Parenting can be confusing and challenging because these children may be able to repeat rules verbatim and yet may not be able to apply them to real-life situations. Behaviors will always have to be viewed through the lens of brain differences, and behavioral therapists need to realize this when planning interventions. School-age children with an FASD may continue to display the same struggles and, in addition, struggle with academic demands. Children with an FASD may struggle in all academic areas, but areas that appear to be most difficult include mathematics, writing, and language arts, not because of poor ability to decode the written word but due to difficulties in understanding abstract language. In addition, children with an FASD may exhibit slow processing of information. Poor attention and executive function may also limit academic progress. In addition, weak visual–spatial skills
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Fig 2. Lip-Philtrum Guides 1 (A) and 2 (B) are used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guides reflect the full range of lip thickness and philtrum depth with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 1 is used for Caucasians and all other races with lips like Caucasians. Guide 2 is used for African Americans and all other races with lips as full as African Americans. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.9
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addressed using social skills training. Finally, children and adolescents with an FASD should have a psychoeducational evaluation to inform implementation of appropriate educational interventions.14
Evaluating Maternal Alcohol Use
Fig 3. Palpebral fissure length (PFL). Distance between the endocanthion and exocanthion landmarks. Copyright 2014, Susan Astley PhD, University of Washington Recommended Legend. The palpebral fissure length (the distance from the inner corner to outer corner of the eye) being measured with a small plastic ruler. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.
and motor skills may adversely impact adaptive daily living skills. This is even more pronounced in the adolescent years when children are expected to do more and more for themselves. Individuals with an FASD may struggle from lack of social boundaries that make close supervision and instruction about boundaries that are mandatory for safety. In adolescence, social immaturity makes them an obvious target for bullies. Parents and teachers should be proactive about these issues and supervise social interactions of children and adolescents with an FASD. These could be
All clinicians should ask about maternal alcohol use, but sometimes it is challenging to obtain a positive history as in the case of foster or adoptive families, the information may be unavailable. Pregnant women or biological mothers may feel stigmatized and therefore hesitant to report alcohol intake during pregnancy. There are available screening tools that are designed to identify risky drinking in pregnant women, one of which is the T-ACE.3,9–11 The T-ACE was discussed extensively in the article on Screening and Brief Interventions. The T-ACE considers any alcohol use during pregnancy as at-risk drinking. If all the diagnostic criteria (face, growth, and CNS) are present, FAS can be diagnosed even when maternal alcohol use is unknown. In order to document the exposure, a clinician could use clinical observation, self-report, reports of heavy alcohol use during pregnancy by a reliable informant, and medical records documenting positive blood alcohol levels or even treatment for alcohol abuse during pregnancy. In addition, any other social, legal, or medical problems related to drinking during the index pregnancy
TABLE 2. CNS functional domains affected in FASD1
Functional domain
Examplesa
Cognitive or developmental deficits or Specific learning disabilities (especially math and/or visual–spatial deficits); uneven profile of cognitive skills; discrepancies poor academic achievement; discrepancy between verbal and nonverbal skills; and slowed movements or reaction to people and stimuli (e.g., poor information processing). Executive functioning deficits Poor organization, planning, or strategy use; concrete thinking; lack of inhibition; difficulty grasping cause and effect; inability to delay gratification; difficulty following multi-step directions; difficulty changing strategies or thinking of things in a different way (i.e., perseveration); poor judgment; and inability to apply knowledge to new situations. Motor functioning delays Delayed motor milestones; difficulty with writing or drawing; clumsiness; balance problems; tremors; and poor dexterity. For infants, a poor suck is often observed. Attention deficit or hyperactivity Described as “busy”; inattentive; easily distracted; difficulty calming down; overly active; difficulty completing tasks; and/or trouble with transitions. Parents might report inconsistency in attention from day to day (e.g., “on” days and “off” days). Poor social skills Lack of stranger fear; often the scapegoat; naiveté and gullibility; easily taken advantage of; inappropriate choice of friends; preference for younger friends; immaturity; superficial interactions; adaptive skills significantly below cognitive potential; inappropriate sexual behaviors; difficulty understanding the perspective of others; poor social cognition; and clinically significant inappropriate initiations or interactions. Other Sensory problems (e.g., tactile defensiveness and oral sensitivity); pragmatic language problems (e.g., difficulty reading facial expressions and poor ability to understand the perspectives of others); memory deficits (e.g., forgetting well-learned material and needing many trials to remember); and difficulty responding appropriately to common parenting practices (e.g., not understanding cause-and-effect discipline). a
These examples are not exhaustive or mutually exclusive. All domains should be assessed using norm-referenced standardized measures and by appropriate professionals using reliable and validated instruments.
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TABLE 3. Differential diagnosis of craniofacial features found in Fetal alcohol syndrome (Adapted from multiple sources)1,22,24,25
Syndromes
Overlapping features
Difference from FAS
Fetal hydantoin Maternal PKU effects
Hypertelorism, flat nasal bridge Epicanthal folds, short palpebral fissures, a long smooth philtrum, and a thin vermillion border A long philtrum, a thin upper lip, an upturned nose, and a depressed nasal bridge A small upturned nose, hypertelorism, a broad philtrum, and maxillary hypoplasia Short palpebral fissures, a smooth philtrum, a thin vermillion border, and midface hypoplasia Prenatal growth restriction, flat midface, and microcephaly Prenatal growth deficiency, microcephaly, hypertelorism, and short palpebral fissures Short palpebral fissures, upturned nostrils, long philtrum, a flat nasal bridge, and epicanthal folds
A short nose and a bowed upper lip A prominent glabella, rounded facies, and a small upturned nose Synophrys, long eyelashes downturned corners of mouth, high arched palate, and short limbs Rounded face, downslanting palpebral fissures, rounded face, widow's peak, and dental eruption problems A large anterior fontanel, micrognathia, downturned corners of mouth, bifrontal narrowing, and ear anomalies Telangiectatic erythema of the face, skin pigmentary abnormalities, and a tendency to develop malignancies Infantile eczema, a high-pitched hoarse cry, limb anomalies, variable ptosis, and cryptorchidism Wide mouth with full lower lip and periorbital fullness, stellate irises, connective tissue disorder, and a hoarse voice Downslanting, palpebral fissures, ptosis of eyes, a wide mouth, keratoconus, webbed neck, low nuchal hairline, pectus excavatum, pulmonic stenosis Broad bulbous nose, wide columella, prominent eyes in infancy, and deep-set eyes in older children Cranial asymmetry, widow's peak, and grooving of the nasal tip Round full face and gradual coarsening of face with growth
Cornelia de Lange Aarskog Toluene embryopathy Bloom syndrome Dubowitz syndrome Williams syndrome
Noonan syndrome
Hypertelorism, a flat nasal bridge, and epicanthal folds
Floating–Harbor syndrome Opitz syndrome
A smooth philtrum and thin lips
Geleophysic dysplasia Fetal valproate effects Miller–Dieker syndrome FG syndrome
Hypertelorism, smooth philtrum, short, palpebral fissures, and anteverted nostrils A thin vermillion border, a long smooth philtrum, a short nose, and anteverted nares Epicanthal folds, a long philtrum with a thin vermillion border, upturned nostrils, and telecanthus A thin vermillion border and a small nose with anteverted nostrils Short palpebral fissures and Hypertelorism
would be high risk for potential use. For ND-PAE, since the other physical criteria may not be present, in order to make the diagnosis, there should be history of more than minimal amounts of alcohol intake during pregnancy, which means “no more than 1–13 drinks per month and no more than 2 drinks per occasion.” Although ND-PAE cannot be diagnosed when alcohol intake does not meet the above criteria, there is no known safe amount or timing of alcohol use during pregnancy.
Other Physical Findings in FAS/FASDs As noted above, three facial features are considered to be central to the diagnosis of FAS: short palpebral fissures, a thin vermillion border or upper lip, and a smooth or flattened philtrum.9,15,16 A number of other physical anomalies are associated with but not necessarily unique to prenatal alcohol exposure. These include epicanthal folds, ptosis, strabismus, “railroad track” ears, small upturned nose, flattened nasal bridge, maxillary hypoplasia, dental malocclusions, cleft palate, narrow- or high-arched palates, “hockey stick” or Curr Probl PediatrAdolesc Health Care, April 2014
High forehead, a narrow bifrontal diameter, and an infraorbital groove or crease Vertical ridging and furrowing in the central forehead, bitemporal narrowing, and variable high forehead Large anterior fontanel, prominent
other abnormal palmar creases, camptodactyly and clinodactyly, nail hypoplasia, joint contractures, and cardiac defects.17–21
Differential Diagnosis of FAS/FASDs Some of the craniofacial features that make up the facial dysmorphia of FAS may be confused with other genetic or teratogenic syndromes. The craniofacial features of FAS that may be confused with other syndromes are smooth philtrum (the University of Washington Lip–Philtrum rank 4 or 5), thin vermillion border (ranks 4 or 5), and short palpebral fissures (at or below the 10th percentile for racial norm). Smooth philtrum is seen in Opitz syndrome, Cornelia de Lange syndrome, Toluene embryopathy, Floating–Harbor syndrome, and Geleophysic dysplasia. Thin vermillion border is seen in Miller–Dieker syndrome, Cornelia de Lange syndrome, Toluene embryopathy, Geleophysic dysplasia, and fetal valproic syndrome. Short palpebral fissures are features of Toluene embryopathy, Williams syndrome, Trisomy 18 syndrome, maternal phenylketonuria (PKU) fetal effects, Campomelic dysplasia,
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TABLE 4. Differential diagnosis of neurobehavioral features in fetal alcohol syndrome1,
3, 4, 6–10, 12–21
(Adapted from multiple sources)22,25
Syndromes
Overlapping features
Difference from FAS
22q11 deletion
Learning disabilities, speech deficits, and low normal-tomild intellectual disabilities
Opitz syndrome
Mild-to-moderate intellectual disability
Fragile X syndrome
ADHD and speech–language deficits
Turner syndrome
Low normal IQ, difficulties with math and problem solving, and hearing impairment
Psychiatric disorders in 10% of patients, velopharyngeal insufficiency, T-cell dysfunction, parathyroid problems, conotruncal heart defects, and strong social skills Intellectual disability is usually associated with structural CNS deficits Hand flapping, poor eye contact, autism, and more severe intellectual disability Performance better in relation to IQ level
Chromosome deletion Syndromes 16p11
10p
Developmental delay more with expressive language delay, ADHD, variable intellectual disability, and autism spectrum disorder Variable developmental delay, hyperactivity Hypotonia
Deep-set eyes, open mouth due to low muscle tone, and PDA Hypoparathyroidism, deafness, renal anomalies, and cardiac abnormalities
Astley, Susan. Palpebral fissure picture [has consent—will be released to Elsevier]. Jones KL, Jones M, Campo M. Smith’s Recognizable Patterns in Human Malformations 6th ed: Elsevier Saunders; 2007. Stoler JM, Holmes LB. Recognition of facial features of fetal Alcohol Syndrome in the Newborn. Am J Med Genet (Semin Med Genet). 2004;127C:21–27. Thackray HM, Tifft C. Fetal Alcohol Syndrome. Pediatr Rev. 2001;22:47–55.
22Q11.2 deletion syndrome, Opitz syndrome, FG syndrome, Dubowitz syndrome, chromosome 10q duplication syndrome, chromosome 15q duplication syndrome, and Oculodentodigital syndrome.1,22 Some of the neurobehavioral features of FAS may be seen in syndromes such as Fragile X syndrome, 22Q11 deletion syndrome, Opitz syndrome, Turner syndrome,1 and even in traumatic brain disorder, but the triad of problems in neurocognition, poor adaptive skills, and poor self-regulation have been recognized by many experts as common features of the FASDs. Further research needs to examine the level of specificity of this triad of findings, and this is one of the conditions under study in the Diagnosis and Statistical Manual of Mental Disorders-5 (DSM-5). Prenatal and/or postnatal growth deficiency is seen in several chromosome and single gene disorder syndromes. Several of these syndromes have other features that help the diagnostician to discriminate them from FAS and the FASDs.22 Tables 3 and 4 summarize some of the genetic syndromes with overlapping craniofacial or neurobehavioral features with FAS.
Summary FASDs are the most common preventable cause of developmental and intellectual disabilities in the United States and yet can easily be overlooked in
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pediatric and adolescent practices. Early diagnosis, presence of developmental and educational services, and a nurturing home environment have been associated with decreased occurrence of secondary disabilities such as substance use and criminal involvement.23 Therefore, it is important for providers to know how to go about the identification, diagnostic, and evaluation process. Pediatric care clinicians should be knowledgeable about the diagnostic criteria for fetal alcohol syndrome and know common differentiating conditions. Furthermore, they should be able to recognize other disorders on the spectrum, and in doing so, they should facilitate appropriate referral, initial management, and coordination of care.
References 1. Bertrand J, Floyd RL, Weber MK, et al. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Atlanta, GA: Centers for Disease Control and Prevention, 2004. 2. Astley figure 1—pictures of children with FAS. 3. Stratton K, Howe C, Battaglia F, eds. Institute of Medicine Report. FAS: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, DC: National Academy Press, 1996. 4. Burgess D,Streissguth AP. Educating students with FAS/FAE. Pennsylvania Reporter. 22(1):2211. 5. Hoyme HE, May PA, Kalberg WO, et al. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 Institute of Medicine criteria. Pediatrics 2005;115:39–47.
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6. American Psychiatric Association. 2013 Diagnostic and Statistical Manual (DSM)-V. 5th ed. 798–99. 7. Kable J. Neurodevelopmental disorders associated with prenatal alcohol exposure (ND-PAE). Presentation to the American Academy of Pediatrics (AAP) Alcohol Related Neurodevelopmental Disorders (ARND) Work Group Meeting. May 1, 2013. 8. Bookstein FL, Connor PD, Sampson PD, Streissguth AP. Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage. Anat Rec 2002;269:162–74. 9. Astley SJ. Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code. 3rd ed. Seattle, WA: University of Washington, 2004. 10. FAS Diagnostic and Prevention Network. 〈http://depts.washing ton.edu/fasdpn/htmls/lip-philtrum-guides.htm〉 Accessed 15.06.13. 11. 〈http://depts.washington.edu/fasdpn/pdfs/astley-pfl-zscore-cal culator.xls〉. 12. Senturias Y, Vincent V, and the AAP FASD expert panel. AAP FASD pedialink. 〈http://pedialink.aap.org/visitor/cme/cmedetail?guid=1ACDFA6F-71BC-4631-A8C0-F20A78AEAA27〉. 2011. 13. ARND consensus in primary care. 〈http://www.niaaa.nih.gov/sites/ default/files/ARNDConferenceConsensusStatementBooklet_ Complete.pdf〉; 2011. 14. FASD Regional Training Centers Curriculum Development Team. Fetal Alcohol Spectrum Disorders Competency-Based Curriculum Development Guide for Medical and Allied Health Education and Practice. Atlanta, GA: Centers for Disease Control and Prevention, 2009. 15. Astley SJ, Clarren SK. Diagnosing the full spectrum of fetal alcohol exposed individuals: introducing the 4-digit diagnostic code. Alcohol Alcohol 2000;35(4):400–10.
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16. Astley SJ, Clarren SK. Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction. Alcohol Alcohol 2001;36(2):147–59. 17. Autti-RämöI, Fagerlunch A, Ervalahti N, Loimu L, Korkman M, Hoyme HE. Fetal alcohol spectrum disorders in Finland: clinical delineation of 77 older children and adolescents. Am J Med Genet 2006;140(2):137–43. 18. Church MW, Eldis F, Blakley BW, Bawle EV. Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcohol Clin Exp Res 1997;21(3):227–37. 19. Jones KL. From recognition to responsibility: Josef Warkany, David Smith, and the fetal alcohol syndrome in the 21st century. Birth Defects Res A Clin Mol Teratol 2003;67(1): 13–20. 20. Jones KL, Smith DW, Ulleland CN, Streissguth AP. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1973;301(7815):1267–71. 21. May PA, Fiorentino J, Gossage JP, et al. Epidemiology of FASD in a province in Italy: prevalence of characteristics of children in a random sample of schools. Alcohol Clin Exp Res 2006;30(9):1562–75. 22. Jones KL, Jones M, Campo M. Smith's Recognizable Patterns in Human Malformations. 6th ed. Elsevier Saunders, 2007. 23. Streissguth AP. Fetal Alcohol Syndrome: A Guide for Families and Communities. Baltimore, Maryland: Paul Brookes Publishing Co, 1997. 24. Stoler JM, Holmes LB. Recognition of facial features of fetal Alcohol Syndrome in the Newborn. Am J Med Genet (Semin Med Genet) 2004;127C:21–7. 25. Thackray HM, Tifft C. Fetal Alcohol Syndrome. Pediatrics in Review 2001;22:47–55.
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Fetal Alcohol Spectrum Disorders: Guidance for Recognition, Diagnosis, Differential Diagnosis and Referral Yasmin Senturias, MD, FAAP,a,b,c and Alexander Asamoah, MD, PhDd
etal alcohol syndrome (FAS) is defined by specific diagnostic criteria as delineated by the National Center on Birth Defects and Developmental Disabilities (NCBDD), Centers for Disease Control and Prevention (CDC), and the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect1 (Table 1)1 (Fig 1).2 It is one of the most common causes of developmental and intellectual disabilities in the US, occurring in 0.2–1.5/1000 births in the United States.3 Symptoms can range in severity but usually include a combination of physical, neurological, behavior, and learning problems. Children with the characteristic facial features, growth deficits, and central nervous system (CNS) abnormalities meet the criteria for FAS with or without documented prenatal alcohol exposure. For other disorders in the spectrum, as originally outlined by the Institute of Medicine (IOM), the full facial, growth, and CNS criteria for FAS may not be met but there must be confirmation of prenatal alcohol exposure. This is a narrow set of criteria that can miss many patients who have neurocognitive effects from alcohol exposure but do not have the classic triad essential for the diagnosis of FAS. In fact, research has shown that children who were exposed to alcohol in utero but do not meet the criteria for FAS have similar cognitive and behavioral characteristics.4
F
From the aDevelopmental-Behavioral Pediatrics Program, Levine Children's Hospital, Charlotte, NC; bDevelopmental and Behavioral Pediatrics of the Carolinas-Charlotte, Carolinas Healthcare System, Charlotte, NC; c Department of Pediatrics, University of North Carolina, Charlotte, NC; and dUniversity of Louisville, Louisville, KY. Curr Probl Pediatr Adolesc Health Care 2014;44:88-95 1538-5442/$ - see front matter & 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.cppeds.2013.12.008
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Other disorders on the spectrum include AlcoholRelated Neurodevelopmental Disorder (ARND), Partial FAS (PFAS), and Alcohol-Related Birth Defects (ARBD). Using the revised Institute of Medicine Criteria set forth by Hoyme et al.,5 ARND can be diagnosed in children with normal growth and structural development and who have characteristic cognitive or neurobehavioral abnormalities that are typical of prenatal alcohol exposure, including problems in executive functioning, communication, emotional lability, motor dysfunction, poor academic performance, deficits in social interactions, and unusual physiologic responses (including problems in sleep and hyperresponsiveness to sensory stimuli). Neurodevelopmental Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) is the new terminology that has been proposed in the Diagnostic and Statistical Manual (DSM) V, and the criteria for the ND-PAE diagnosis is listed in the appendix of DSM-V. The proposed criteria includes that the patient was “exposed to alcohol at any time during gestation, including prior to pregnancy recognition and the exposure level was more than minimal”6 along with presence of neurocognitive impairment, impairment in self-regulation, and impairment in adaptive functioning. Minimal intake means “no more than 1–13 drinks per month and no more than 2 drinks per occasion.”6 Neurocognitive impairments in ND-PAE include global intellectual impairment, impairment in executive functioning, impairment in learning, impairment in memory, and impairment in visual–spatial reasoning. Impairment in self-regulation includes impairment in mood or behavioral regulation, attention deficit, and impairment in impulse control. Deficits in adaptive functioning include communication deficit, social impairment, impairment in daily living, and motor impairment.6,7 PFAS is diagnosed in the presence of facial
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TABLE 1. The criteria for FAS diagnosis1
A. Requires all three of the following findings: 1. Documentation of all three facial abnormalities (smooth philtrum, thin vermillion, and small palpebral fissures). 2. Documentation of growth deficits. 3. Documentation of CNS abnormality. B. Facial dysmorphia. Based on racial norms, individual exhibits all three characteristic facial features: 1. Smooth philtrum (the University of Washington Lip–Philtrum Guide rank 4 or 5). 2. Thin vermillion border (the University of Washington Lip–Philtrum Guide rank 4 or 5). 3. Small palpebral fissures (at or below the 10th percentile). C. Growth problems. Confirmed prenatal or postnatal height, or weight, or both, at or below the 10th percentile, documented at any one point in time (adjusted for age, sex, gestational age, and race or ethnicity). D. Central nervous system abnormalities Structural Head circumference (OFC) at or below the 10th percentile adjusted for age and sex. Clinically significant brain abnormalities observable through imaging. Neurological Neurological problems not due to a postnatal insult or fever or other soft neurological signs outside normal limits. Functional Performance substantially below that expected for an individual's age, schooling, or circumstances, as evidenced by the following: 1. Global cognitive or intellectual deficits representing multiple domains of deficit (or significant developmental delay in younger children) with performance below the 3rd percentile (2 standard deviations below the mean for standardized testing). OR 2. Functional deficits below the 16th percentile (1 standard deviation below the mean for standardized testing) in at least three of the following domains: Cognitive or developmental deficits or discrepancies. Executive functioning deficits. Motor functioning delays. Problems with attention or hyperactivity. Poor social skills. Other (e.g., sensory problems, pragmatic language problems, or memory deficits). E. Maternal alcohol exposure 1. Confirmed prenatal alcohol exposure. 2. Unknown prenatal alcohol exposure.
characteristics that meet the criteria for FAS and abnormalities in either in growth or in the CNS domain.5 ARBDs are diagnosed when there is confirmed exposure to alcohol in utero, normal growth, the typical facial characteristics, and specific structural abnormalities (either major malformations or a pattern of minor
malformations).5 It is now known that relying on facial features for the identification of children with FASDs largely underidentifies the population of all alcoholexposed pregnancies as the vast majority of individuals exposed to alcohol during pregnancy do not present with the FAS facial phenotype but rather with the CNS
Fig 1. Examples of the FAS facial phenotype (small eyes, smooth philtrum, and thin upper lip) across three races: (A) Caucasian, (B) Native American, (C) African American. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.9
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effects.8 Of all the conditions in the spectrum, ARND (more currently referenced as ND-PAE) is estimated to be 10 times more common than FAS.3
The Facial and the Growth Criteria in FAS The facial and the growth criteria are quite straightforward, but in order to evaluate the facial criteria, it is helpful to use the following: a clear plastic ruler with blunt edges and the University of Washington Lip– Philtrum guides (Fig 2).9 The Lip–Philtrum Guide (www.fasdpn.org)10 is a 5-point pictorial scale that measures the smoothness of the philtrum and the thinness of the upper lip. A rank of “1” on the scale depicts a deeply grooved philtrum and a thick upper lip; a rank of “5” depicts a smooth philtrum and thin upper lip that is characteristic of a child with FAS. There are two lip– philtrum guides. Guide 1 is used for Caucasians and all other races with lips similar to Caucasians. Guide 2 is used for African-American and all other races with lips as full as African-Americans. FAS facial features require a Rank 4 or Rank 5 lip and philtrum (Fig 2).9 Palpebral fissure length is measured using a clear plastic ruler from the inner to outer corners of the eye (the endocanthion to the exocanthion) (Fig 3)9 and then the measurement is compared to a nomogram or plotted in an excel file using the following link: http://depts.washington.edu/fasdpn/ pdfs/astley-pfl-zscore-calculator.xls11; these would account for variations due to age. Further training on the diagnosis of facial criteria can be obtained by accessing the American Academy of Pediatrics FASD Pedialink at aap.org/fasd12 or the 4-Digit Diagnostic Code of the University of Washington.9 As defined in the 2004 NCBDD-CDC National Task Force guidelines, the growth criteria requires the usual height and weight measures and is positive when there is confirmed prenatal or postnatal height, weight, or both at or below the 10th percentile documented at any point in time and adjusted for age, sex, gestational age, race, ethnicity, and even nutritional or genetic factors, when applicable.
The CNS Criteria for FAS The CNS criteria for FAS can be met by documenting structural, neurological, or functional abnormality in FAS. The structural criteria are met either when there is a small head size (head size at or below the 10th percentile) or when there are structural
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abnormalities seen on imaging. Neurological abnormalities can be seen on exam and can consist of either focal findings (such as tremor) or unprovoked seizures. The CNS functional abnormalities are often best gauged by how the child thinks, learns, and behaves, as well as by reviewing information obtained from neuropsychological or developmental testing. Examples of CNS abnormalities are seen in Table 2.1 In infancy, the CNS dysfunction may be characterized by poor suck and irritability. These infants may benefit from nutritional support and from decreasing environmental overstimulation. Toddlers with an FASD may appear to be very busy and distractible and may have problems with balance and coordination. They may also have difficulties in sleep and in managing sensory stimuli, and these items need to be noted by clinicians. Difficulties in sleep and in managing sensory stimuli may be manageable by guidance in the medical home but referrals to a sleep clinic and to an occupational therapy, respectively, may also be necessary. The toddler's difficulties with comprehension and problem solving may result in prolonged tantrums. This problem becomes more evident in the preschool years when children are expected to have more self-regulation abilities. In fact, poor “self-soothing” appears to be one of the most common presenting symptoms of an alcohol-related neurodevelopmental disorder.13 Although early expressive language milestones may be normal, comprehension and understanding of concepts may lag behind and require language therapy. Furthermore, causeand-effect reasoning is less efficient for children with FASDs, making it more difficult for them to learn from past experience. Parenting can be confusing and challenging because these children may be able to repeat rules verbatim and yet may not be able to apply them to real-life situations. Behaviors will always have to be viewed through the lens of brain differences, and behavioral therapists need to realize this when planning interventions. School-age children with an FASD may continue to display the same struggles and, in addition, struggle with academic demands. Children with an FASD may struggle in all academic areas, but areas that appear to be most difficult include mathematics, writing, and language arts, not because of poor ability to decode the written word but due to difficulties in understanding abstract language. In addition, children with an FASD may exhibit slow processing of information. Poor attention and executive function may also limit academic progress. In addition, weak visual–spatial skills
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Fig 2. Lip-Philtrum Guides 1 (A) and 2 (B) are used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guides reflect the full range of lip thickness and philtrum depth with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 1 is used for Caucasians and all other races with lips like Caucasians. Guide 2 is used for African Americans and all other races with lips as full as African Americans. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.9
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addressed using social skills training. Finally, children and adolescents with an FASD should have a psychoeducational evaluation to inform implementation of appropriate educational interventions.14
Evaluating Maternal Alcohol Use
Fig 3. Palpebral fissure length (PFL). Distance between the endocanthion and exocanthion landmarks. Copyright 2014, Susan Astley PhD, University of Washington Recommended Legend. The palpebral fissure length (the distance from the inner corner to outer corner of the eye) being measured with a small plastic ruler. Copyright 2014, Susan Astley PhD, University of Washington. Copyright of the Picture(s) is not being released to the authors or publisher, only permission to incorporate it as described here.
and motor skills may adversely impact adaptive daily living skills. This is even more pronounced in the adolescent years when children are expected to do more and more for themselves. Individuals with an FASD may struggle from lack of social boundaries that make close supervision and instruction about boundaries that are mandatory for safety. In adolescence, social immaturity makes them an obvious target for bullies. Parents and teachers should be proactive about these issues and supervise social interactions of children and adolescents with an FASD. These could be
All clinicians should ask about maternal alcohol use, but sometimes it is challenging to obtain a positive history as in the case of foster or adoptive families, the information may be unavailable. Pregnant women or biological mothers may feel stigmatized and therefore hesitant to report alcohol intake during pregnancy. There are available screening tools that are designed to identify risky drinking in pregnant women, one of which is the T-ACE.3,9–11 The T-ACE was discussed extensively in the article on Screening and Brief Interventions. The T-ACE considers any alcohol use during pregnancy as at-risk drinking. If all the diagnostic criteria (face, growth, and CNS) are present, FAS can be diagnosed even when maternal alcohol use is unknown. In order to document the exposure, a clinician could use clinical observation, self-report, reports of heavy alcohol use during pregnancy by a reliable informant, and medical records documenting positive blood alcohol levels or even treatment for alcohol abuse during pregnancy. In addition, any other social, legal, or medical problems related to drinking during the index pregnancy
TABLE 2. CNS functional domains affected in FASD1
Functional domain
Examplesa
Cognitive or developmental deficits or Specific learning disabilities (especially math and/or visual–spatial deficits); uneven profile of cognitive skills; discrepancies poor academic achievement; discrepancy between verbal and nonverbal skills; and slowed movements or reaction to people and stimuli (e.g., poor information processing). Executive functioning deficits Poor organization, planning, or strategy use; concrete thinking; lack of inhibition; difficulty grasping cause and effect; inability to delay gratification; difficulty following multi-step directions; difficulty changing strategies or thinking of things in a different way (i.e., perseveration); poor judgment; and inability to apply knowledge to new situations. Motor functioning delays Delayed motor milestones; difficulty with writing or drawing; clumsiness; balance problems; tremors; and poor dexterity. For infants, a poor suck is often observed. Attention deficit or hyperactivity Described as “busy”; inattentive; easily distracted; difficulty calming down; overly active; difficulty completing tasks; and/or trouble with transitions. Parents might report inconsistency in attention from day to day (e.g., “on” days and “off” days). Poor social skills Lack of stranger fear; often the scapegoat; naiveté and gullibility; easily taken advantage of; inappropriate choice of friends; preference for younger friends; immaturity; superficial interactions; adaptive skills significantly below cognitive potential; inappropriate sexual behaviors; difficulty understanding the perspective of others; poor social cognition; and clinically significant inappropriate initiations or interactions. Other Sensory problems (e.g., tactile defensiveness and oral sensitivity); pragmatic language problems (e.g., difficulty reading facial expressions and poor ability to understand the perspectives of others); memory deficits (e.g., forgetting well-learned material and needing many trials to remember); and difficulty responding appropriately to common parenting practices (e.g., not understanding cause-and-effect discipline). a
These examples are not exhaustive or mutually exclusive. All domains should be assessed using norm-referenced standardized measures and by appropriate professionals using reliable and validated instruments.
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TABLE 3. Differential diagnosis of craniofacial features found in Fetal alcohol syndrome (Adapted from multiple sources)1,22,24,25
Syndromes
Overlapping features
Difference from FAS
Fetal hydantoin Maternal PKU effects
Hypertelorism, flat nasal bridge Epicanthal folds, short palpebral fissures, a long smooth philtrum, and a thin vermillion border A long philtrum, a thin upper lip, an upturned nose, and a depressed nasal bridge A small upturned nose, hypertelorism, a broad philtrum, and maxillary hypoplasia Short palpebral fissures, a smooth philtrum, a thin vermillion border, and midface hypoplasia Prenatal growth restriction, flat midface, and microcephaly Prenatal growth deficiency, microcephaly, hypertelorism, and short palpebral fissures Short palpebral fissures, upturned nostrils, long philtrum, a flat nasal bridge, and epicanthal folds
A short nose and a bowed upper lip A prominent glabella, rounded facies, and a small upturned nose Synophrys, long eyelashes downturned corners of mouth, high arched palate, and short limbs Rounded face, downslanting palpebral fissures, rounded face, widow's peak, and dental eruption problems A large anterior fontanel, micrognathia, downturned corners of mouth, bifrontal narrowing, and ear anomalies Telangiectatic erythema of the face, skin pigmentary abnormalities, and a tendency to develop malignancies Infantile eczema, a high-pitched hoarse cry, limb anomalies, variable ptosis, and cryptorchidism Wide mouth with full lower lip and periorbital fullness, stellate irises, connective tissue disorder, and a hoarse voice Downslanting, palpebral fissures, ptosis of eyes, a wide mouth, keratoconus, webbed neck, low nuchal hairline, pectus excavatum, pulmonic stenosis Broad bulbous nose, wide columella, prominent eyes in infancy, and deep-set eyes in older children Cranial asymmetry, widow's peak, and grooving of the nasal tip Round full face and gradual coarsening of face with growth
Cornelia de Lange Aarskog Toluene embryopathy Bloom syndrome Dubowitz syndrome Williams syndrome
Noonan syndrome
Hypertelorism, a flat nasal bridge, and epicanthal folds
Floating–Harbor syndrome Opitz syndrome
A smooth philtrum and thin lips
Geleophysic dysplasia Fetal valproate effects Miller–Dieker syndrome FG syndrome
Hypertelorism, smooth philtrum, short, palpebral fissures, and anteverted nostrils A thin vermillion border, a long smooth philtrum, a short nose, and anteverted nares Epicanthal folds, a long philtrum with a thin vermillion border, upturned nostrils, and telecanthus A thin vermillion border and a small nose with anteverted nostrils Short palpebral fissures and Hypertelorism
would be high risk for potential use. For ND-PAE, since the other physical criteria may not be present, in order to make the diagnosis, there should be history of more than minimal amounts of alcohol intake during pregnancy, which means “no more than 1–13 drinks per month and no more than 2 drinks per occasion.” Although ND-PAE cannot be diagnosed when alcohol intake does not meet the above criteria, there is no known safe amount or timing of alcohol use during pregnancy.
Other Physical Findings in FAS/FASDs As noted above, three facial features are considered to be central to the diagnosis of FAS: short palpebral fissures, a thin vermillion border or upper lip, and a smooth or flattened philtrum.9,15,16 A number of other physical anomalies are associated with but not necessarily unique to prenatal alcohol exposure. These include epicanthal folds, ptosis, strabismus, “railroad track” ears, small upturned nose, flattened nasal bridge, maxillary hypoplasia, dental malocclusions, cleft palate, narrow- or high-arched palates, “hockey stick” or Curr Probl PediatrAdolesc Health Care, April 2014
High forehead, a narrow bifrontal diameter, and an infraorbital groove or crease Vertical ridging and furrowing in the central forehead, bitemporal narrowing, and variable high forehead Large anterior fontanel, prominent
other abnormal palmar creases, camptodactyly and clinodactyly, nail hypoplasia, joint contractures, and cardiac defects.17–21
Differential Diagnosis of FAS/FASDs Some of the craniofacial features that make up the facial dysmorphia of FAS may be confused with other genetic or teratogenic syndromes. The craniofacial features of FAS that may be confused with other syndromes are smooth philtrum (the University of Washington Lip–Philtrum rank 4 or 5), thin vermillion border (ranks 4 or 5), and short palpebral fissures (at or below the 10th percentile for racial norm). Smooth philtrum is seen in Opitz syndrome, Cornelia de Lange syndrome, Toluene embryopathy, Floating–Harbor syndrome, and Geleophysic dysplasia. Thin vermillion border is seen in Miller–Dieker syndrome, Cornelia de Lange syndrome, Toluene embryopathy, Geleophysic dysplasia, and fetal valproic syndrome. Short palpebral fissures are features of Toluene embryopathy, Williams syndrome, Trisomy 18 syndrome, maternal phenylketonuria (PKU) fetal effects, Campomelic dysplasia,
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TABLE 4. Differential diagnosis of neurobehavioral features in fetal alcohol syndrome1,
3, 4, 6–10, 12–21
(Adapted from multiple sources)22,25
Syndromes
Overlapping features
Difference from FAS
22q11 deletion
Learning disabilities, speech deficits, and low normal-tomild intellectual disabilities
Opitz syndrome
Mild-to-moderate intellectual disability
Fragile X syndrome
ADHD and speech–language deficits
Turner syndrome
Low normal IQ, difficulties with math and problem solving, and hearing impairment
Psychiatric disorders in 10% of patients, velopharyngeal insufficiency, T-cell dysfunction, parathyroid problems, conotruncal heart defects, and strong social skills Intellectual disability is usually associated with structural CNS deficits Hand flapping, poor eye contact, autism, and more severe intellectual disability Performance better in relation to IQ level
Chromosome deletion Syndromes 16p11
10p
Developmental delay more with expressive language delay, ADHD, variable intellectual disability, and autism spectrum disorder Variable developmental delay, hyperactivity Hypotonia
Deep-set eyes, open mouth due to low muscle tone, and PDA Hypoparathyroidism, deafness, renal anomalies, and cardiac abnormalities
Astley, Susan. Palpebral fissure picture [has consent—will be released to Elsevier]. Jones KL, Jones M, Campo M. Smith’s Recognizable Patterns in Human Malformations 6th ed: Elsevier Saunders; 2007. Stoler JM, Holmes LB. Recognition of facial features of fetal Alcohol Syndrome in the Newborn. Am J Med Genet (Semin Med Genet). 2004;127C:21–27. Thackray HM, Tifft C. Fetal Alcohol Syndrome. Pediatr Rev. 2001;22:47–55.
22Q11.2 deletion syndrome, Opitz syndrome, FG syndrome, Dubowitz syndrome, chromosome 10q duplication syndrome, chromosome 15q duplication syndrome, and Oculodentodigital syndrome.1,22 Some of the neurobehavioral features of FAS may be seen in syndromes such as Fragile X syndrome, 22Q11 deletion syndrome, Opitz syndrome, Turner syndrome,1 and even in traumatic brain disorder, but the triad of problems in neurocognition, poor adaptive skills, and poor self-regulation have been recognized by many experts as common features of the FASDs. Further research needs to examine the level of specificity of this triad of findings, and this is one of the conditions under study in the Diagnosis and Statistical Manual of Mental Disorders-5 (DSM-5). Prenatal and/or postnatal growth deficiency is seen in several chromosome and single gene disorder syndromes. Several of these syndromes have other features that help the diagnostician to discriminate them from FAS and the FASDs.22 Tables 3 and 4 summarize some of the genetic syndromes with overlapping craniofacial or neurobehavioral features with FAS.
Summary FASDs are the most common preventable cause of developmental and intellectual disabilities in the United States and yet can easily be overlooked in
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pediatric and adolescent practices. Early diagnosis, presence of developmental and educational services, and a nurturing home environment have been associated with decreased occurrence of secondary disabilities such as substance use and criminal involvement.23 Therefore, it is important for providers to know how to go about the identification, diagnostic, and evaluation process. Pediatric care clinicians should be knowledgeable about the diagnostic criteria for fetal alcohol syndrome and know common differentiating conditions. Furthermore, they should be able to recognize other disorders on the spectrum, and in doing so, they should facilitate appropriate referral, initial management, and coordination of care.
References 1. Bertrand J, Floyd RL, Weber MK, et al. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Atlanta, GA: Centers for Disease Control and Prevention, 2004. 2. Astley figure 1—pictures of children with FAS. 3. Stratton K, Howe C, Battaglia F, eds. Institute of Medicine Report. FAS: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, DC: National Academy Press, 1996. 4. Burgess D,Streissguth AP. Educating students with FAS/FAE. Pennsylvania Reporter. 22(1):2211. 5. Hoyme HE, May PA, Kalberg WO, et al. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 Institute of Medicine criteria. Pediatrics 2005;115:39–47.
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6. American Psychiatric Association. 2013 Diagnostic and Statistical Manual (DSM)-V. 5th ed. 798–99. 7. Kable J. Neurodevelopmental disorders associated with prenatal alcohol exposure (ND-PAE). Presentation to the American Academy of Pediatrics (AAP) Alcohol Related Neurodevelopmental Disorders (ARND) Work Group Meeting. May 1, 2013. 8. Bookstein FL, Connor PD, Sampson PD, Streissguth AP. Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage. Anat Rec 2002;269:162–74. 9. Astley SJ. Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code. 3rd ed. Seattle, WA: University of Washington, 2004. 10. FAS Diagnostic and Prevention Network. 〈http://depts.washing ton.edu/fasdpn/htmls/lip-philtrum-guides.htm〉 Accessed 15.06.13. 11. 〈http://depts.washington.edu/fasdpn/pdfs/astley-pfl-zscore-cal culator.xls〉. 12. Senturias Y, Vincent V, and the AAP FASD expert panel. AAP FASD pedialink. 〈http://pedialink.aap.org/visitor/cme/cmedetail?guid=1ACDFA6F-71BC-4631-A8C0-F20A78AEAA27〉. 2011. 13. ARND consensus in primary care. 〈http://www.niaaa.nih.gov/sites/ default/files/ARNDConferenceConsensusStatementBooklet_ Complete.pdf〉; 2011. 14. FASD Regional Training Centers Curriculum Development Team. Fetal Alcohol Spectrum Disorders Competency-Based Curriculum Development Guide for Medical and Allied Health Education and Practice. Atlanta, GA: Centers for Disease Control and Prevention, 2009. 15. Astley SJ, Clarren SK. Diagnosing the full spectrum of fetal alcohol exposed individuals: introducing the 4-digit diagnostic code. Alcohol Alcohol 2000;35(4):400–10.
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16. Astley SJ, Clarren SK. Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction. Alcohol Alcohol 2001;36(2):147–59. 17. Autti-RämöI, Fagerlunch A, Ervalahti N, Loimu L, Korkman M, Hoyme HE. Fetal alcohol spectrum disorders in Finland: clinical delineation of 77 older children and adolescents. Am J Med Genet 2006;140(2):137–43. 18. Church MW, Eldis F, Blakley BW, Bawle EV. Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcohol Clin Exp Res 1997;21(3):227–37. 19. Jones KL. From recognition to responsibility: Josef Warkany, David Smith, and the fetal alcohol syndrome in the 21st century. Birth Defects Res A Clin Mol Teratol 2003;67(1): 13–20. 20. Jones KL, Smith DW, Ulleland CN, Streissguth AP. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1973;301(7815):1267–71. 21. May PA, Fiorentino J, Gossage JP, et al. Epidemiology of FASD in a province in Italy: prevalence of characteristics of children in a random sample of schools. Alcohol Clin Exp Res 2006;30(9):1562–75. 22. Jones KL, Jones M, Campo M. Smith's Recognizable Patterns in Human Malformations. 6th ed. Elsevier Saunders, 2007. 23. Streissguth AP. Fetal Alcohol Syndrome: A Guide for Families and Communities. Baltimore, Maryland: Paul Brookes Publishing Co, 1997. 24. Stoler JM, Holmes LB. Recognition of facial features of fetal Alcohol Syndrome in the Newborn. Am J Med Genet (Semin Med Genet) 2004;127C:21–7. 25. Thackray HM, Tifft C. Fetal Alcohol Syndrome. Pediatrics in Review 2001;22:47–55.
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