Facial characteristics of a child with FAS The key of<unk>  can vary between individuals exposed to<unk>  during pregnancy. While consensus exists for the definition and diagnosis of FAS, minor variations among the systems lead to differences in definitions and diagnostic cut-off criteria for other diagnoses across the<unk>  continuum. The central nervous system damage criteria particularly lacks clear consensus. A working knowledge of the key features is helpful in understanding<unk>  diagnoses and conditions, and each is reviewed with attention to similarities and differences across the four diagnostic systems. More than 400 problems, however, can occur with<unk> . Growth In terms of<unk> , growth deficiency is defined as significantly below average height, weight or both due to prenatal<unk>  exposure and can be assessed at any point in the lifespan. Growth measurements must be adjusted for parental height, gestational age (for a premature infant), and other postnatal insults (e.g., poor nutrition), although birth height and weight are the preferred measurements. Deficiencies are documented when height or weight falls at or below the 10th percentile of standardized growth charts appropriate to the population. Prenatal or postnatal presentation of growth deficits can occur, but are most often postnatal. Criteria for<unk>  are least specific in the Institute of Medicine (IOM) diagnostic system ("low birth weight..., decelerating weight not due to nutrition..., or disproportional low weight to height" p. 4 of executive summary), while the CDC and Canadian guidelines use the 10th percentile as a cut-off to determine growth deficiency. The "4-Digit Diagnostic Code" allows for mid-range gradations in growth deficiency (between the 3rd and 10th percentiles) and severe growth deficiency at or below the 3rd percentile. Growth deficiency (at severe, moderate, or mild levels) contributes to diagnoses of FAS and pFAS, but not ARND or static encephalopathy. Growth deficiency is ranked as follows by the "4-Digit Diagnostic Code": * Severe: Height and weight at or below the 3rd percentile. * Moderate: Either height or weight at or below the 3rd percentile, but not both. * Mild: Either height or weight or both between the 3rd and 10th percentiles. * None: Height and weight both above the 10th percentile. In the initial studies that discovered FAS, growth deficiency was a requirement for inclusion in the studies; thus, all the original people with FAS had growth deficiency as an artifact of sampling characteristics used to establish criteria for the syndrome. That is, growth deficiency is a key feature of<unk>  because growth deficiency was a criterion for inclusion in the study that defined FAS. This suggests growth deficiency may be less critical for understanding the disabilities of<unk>  than the neurobehavioral sequelae to the brain damage. Facial features Several characteristic craniofacial abnormalities are often visible in individuals with FAS. The presence of FAS facial features indicates brain damage, although brain damage may also exist in their absence. FAS facial features (and most other visible, but non-diagnostic, deformities) are believed to be caused mainly during the 10th to 20th week of gestation. Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features known to result from prenatal<unk>  exposure and distinguishes FAS from other<unk> s with partially overlapping characteristics. The three FAS facial features are: * A smooth philtrum: The divot or groove between the nose and upper lip flattens with increased prenatal<unk>  exposure. * Thin vermilion: The upper lip thins with increased prenatal<unk>  exposure. * Small palpebral fissures: Eye width decreases with increased prenatal<unk>  exposure. Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a five-point Likert scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington. Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal<unk> . A summary of the criteria follows: * Severe: All three facial features ranked independently as severe (lip ranked at 4 or 5, philtrum ranked at 4 or 5, and PFL two or more standard deviations below average). * Moderate: Two facial features ranked as severe and one feature ranked as moderate (lip or philtrum ranked at 3, or PFL between one and two standard deviations below average). * Mild: A mild ranking of FAS facial features covers a broad range of facial feature combinations: * Two facial features ranked severe and one ranked within normal limits, * One facial feature ranked severe and two ranked moderate, or * One facial feature ranked severe, one ranked moderate and one ranked within normal limits. * None: All three facial features ranked within normal limits. Central nervous system Central nervous system (CNS) damage is the primary feature of any<unk>  diagnosis. Prenatal<unk>  exposure, which is classified as a teratogen, can damage the brain across a continuum of gross to subtle impairments, depending on the amount, timing, and frequency of the exposure as well as genetic predispositions of the fetus and mother. While functional abnormalities are the behavioral and cognitive expressions of the<unk>  disability, CNS damage can be assessed in three areas: structural, neurological, and functional impairments. All four diagnostic systems allow for assessment of CNS damage in these areas, but criteria vary. The IOM system requires structural or neurological impairment for a diagnosis of FAS, but also allows a "complex pattern" of functional anomalies for diagnosing PFAS and ARND. The "4-Digit Diagnostic Code" and CDC guidelines allow for a positive CNS finding in any of the three areas for any<unk>  diagnosis, but functional anomalies must measure at two standard deviations or worse in three or more functional domains for a diagnosis of FAS, PFAS, and ARND. The "4-Digit Diagnostic Code" also allows for an<unk>  diagnosis when only two functional domains are measured at two standard deviations or worse. The "4-Digit Diagnostic Code" further elaborates the degree of CNS damage according to four ranks: * Definite: Structural impairments or neurological impairments for FAS or static encephalopathy. * Probable: Significant dysfunction of two standard deviations or worse in three or more functional domains. * Possible: Mild to moderate dysfunction of two standard deviations or worse in one or two functional domains or by judgment of the clinical evaluation team that CNS damage cannot be dismissed. * Unlikely: No evidence of CNS damage. Structural Structural abnormalities of the brain are observable, physical damage to the brain or brain structures caused by prenatal<unk>  exposure. Structural impairments may include microcephaly (small head size) of two or more standard deviations below the average, or other abnormalities in brain structure (e.g., agenesis of the corpus callosum, cerebellar hypoplasia). Microcephaly is determined by comparing head circumference (often called occipitofrontal circumference, or OFC) to appropriate OFC growth charts. Other structural impairments must be observed through medical imaging techniques by a trained physician. Because imaging procedures are expensive and relatively inaccessible to most people, diagnosis of FAS is not frequently made via structural impairments, except for microcephaly. Evidence of a CNS structural impairment due to prenatal<unk>  exposure will result in a diagnosis of FAS, and neurological and functional impairments are highly likely. During the first trimester of pregnancy,<unk>  interferes with the migration and organization of brain cells, which can create structural deformities or deficits within the brain. During the third trimester, damage can be caused to the hippocampus, which plays a role in memory, learning, emotion, and encoding visual and auditory information, all of which can create neurological and functional CNS impairments as well. As of 2002, there were 25 reports of autopsies on infants known to have FAS. The first was in 1973, on an infant who died shortly after birth. The examination revealed extensive brain damage, including microcephaly, migration anomalies, callosal dysgenesis, and a massive neuroglial, leptomeningeal heterotopia covering the left hemisphere. In 1977, Dr. Clarren described a second infant whose mother was a binge drinker. The infant died ten days after birth. The autopsy showed severe hydrocephalus, abnormal neuronal migration, and a small corpus callosum (which connects the two brain hemispheres) and cerebellum. FAS has also been linked to brainstem and cerebellar changes, agenesis of the corpus callosum and anterior commissure, neuronal migration errors, absent olfactory bulbs, meningomyelocele, and porencephaly. Neurological When structural impairments are not observable or do not exist, neurological impairments are assessed. In the context of<unk> , neurological impairments are caused by prenatal<unk>  exposure which causes general neurological damage to the central nervous system (CNS), the peripheral nervous system, or the autonomic nervous system. A determination of a neurological problem must be made by a trained physician, and must not be due to a postnatal insult, such as meningitis, concussion, traumatic brain injury, etc. All four diagnostic systems show virtual agreement on their criteria for CNS damage at the neurological level,
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