Developmental milestones and daily living skills in individuals with Angelman syndrome

Abstract

Background: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants.

Methods: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living skills. The Cox Proportional Hazard model was applied to analyze differences in the probability of achievement of skills at various ages among five molecular subtypes of AS.

Results: Almost all individuals, regardless of molecular subtype, were able to walk with support by five years of age. By age 15, those with a deletion had at least a 50% probability of acquiring 17 out of 30 skills compared to 25 out of 30 skills among those without a deletion. Overall, fine and gross motor skills such as holding and reaching for small objects, sitting, and walking with support were achieved within a fairly narrow range of ages, while toileting, feeding, and hygiene skills tend to have greater variability in the ages at which these skills were achieved. Those without a deletion had a higher probability (25-92%) of achieving daily living skills such as independently toileting and dressing compared to those with a deletion (0-13%). Across all molecular subtypes, there was a low probability of achieving independence in bathing and brushing teeth.

Conclusion: Individuals with AS without a deletion are more likely to achieve developmental milestones and daily living skills at an earlier age than those with a deletion. Many individuals with AS are unable to achieve daily living skills necessary for independent self-care.

Keywords: Activities of Daily Living; Child development; Developmental disabilities; Intellectual disability.

Fig. 1

Probability of Skill Achievement for Critical Developmental Milestones and Daily Living Skills by Molecular Subtype Note. Dashed lines indicate point on the curve associated with a 50% probability of achieving the skill. Higher probabilities indicate that more individuals with AS are expected to achieve the skill. Steeper curves indicate that individuals tend to achieve the skill in a relatively narrow age range whereas flatter curves indicate a wide range of ages where individuals achieve the skill

Fig. 2

Probability of Skill Achievement in Class I Deletion From left to right, the first black triangle represents a probability of 0.05, the beginning of the shaded gray bar represents a probability of 0.25, the black circle represents a probability of 0.50, the end of shaded gray bar on the right represents a probability of 0.75, and a second black triangle on the right represents a probability of 0.95. The red X indicates the age at which the milestone is achieved by ≥ 75% children in the general population. For the feeding skill of independent utensil use ("Utensils Independ") the first red X indicates use of a spoon, the second red X indicates use of a fork. The axis on the right indicates the probability of skill achievement. This value is either 0.95, or the probability of skill achievement at 15 years of age in cases where the probability did not reach 0.95

Fig. 3

Probability of Skill Achievement in Class II Deletion From left to right, the first black triangle represents a probability of 0.05, the beginning of the shaded gray bar represents a probability of 0.25, the black circle represents a probability of 0.50, the end of shaded gray bar on the right represents a probability of 0.75, and a second black triangle on the right represents a probability of 0.95. The red X indicates the age at which the milestone is achieved by ≥ 75% children in the general populationFor the feeding skill of independent utensil use ("Utensils Independ") the first red X indicates use of a spoon, the second red X indicates use of a fork. The axis on the right indicates the probability of skill achievement. This value is either 0.95, or the probability of skill achievement at 15 years of age in cases where the probability did not reach 0.95

Fig. 4

Probability of Skill Achievement in UBE3A Mutation From left to right, the first black triangle represents a probability of 0.05, the beginning of the shaded gray bar represents a probability of 0.25, the black circle represents a probability of 0.50, the end of shaded gray bar on the right represents a probability of 0.75, and a second black triangle on the right represents a probability of 0.95. The red X indicates the age at which the milestone is achieved by ≥ 75% children in the general populationFor the feeding skill of independent utensil use ("Utensils Independ") the first red X indicates use of a spoon, the second red X indicates use of a fork. The axis on the right indicates the probability of skill achievement. This value is either 0.95, or the probability of skill achievement at 15 years of age in cases where the probability did not reach 0.95

Fig. 5

Probability of Skill Achievement in Uniparental Disomy From left to right, the first black triangle represents a probability of 0.05, the beginning of the shaded gray bar represents a probability of 0.25, the black circle represents a probability of 0.50, the end of shaded gray bar on the right represents a probability of 0.75, and a second black triangle on the right represents a probability of 0.95. The red X indicates the age at which the milestone is achieved by ≥ 75% children in the general populationFor the feeding skill of independent utensil use ("Utensils Independ") the first red X indicates use of a spoon, the second red X indicates use of a fork. The axis on the right indicates the probability of skill achievement. This value is either 0.95, or the probability of skill achievement at 15 years of age in cases where the probability did not reach 0.95

Fig. 6

Probability of Skill Achievement in Imprinting Defect From left to right, the first black triangle represents a probability of 0.05, the beginning of the shaded gray bar represents a probability of 0.25, the black circle represents a probability of 0.50, the end of shaded gray bar on the right represents a probability of 0.75, and a second black triangle on the right represents a probability of 0.95. The red X indicates the age at which the milestone is achieved by ≥ 75% children in the general populationFor the feeding skill of independent utensil use ("Utensils Independ") the first red X indicates use of a spoon, the second red X indicates use of a fork. The axis on the right indicates the probability of skill achievement. This value is either 0.95, or the probability of skill achievement at 15 years of age in cases where the probability did not reach 0.95