Table 2.
Phenotypes, genotypes, and demographic features of individuals with an AHDC1 missense mutation
| Patient ID | 1 | 3 | 5 | 6 | 7 | 8 | 9 | 10 | |
|---|---|---|---|---|---|---|---|---|---|
| Mutation | |||||||||
| Nucleotide change | c.139C>T | c.1610G>A | c.1646G>A | c.1819G>A | c.2374G>C | c.4042T>C | c. 4370A>G | c.4432C>T | |
| Protein change | p.Pro47Ser | p.Gly537Asp | p.Arg549His | p.Asp607Asn | p.Gly792Arg | p.Ser1348Pro | p.Asp1457Gly | p.Pro1478Ser | |
| Age | 14 years | 10 years | 6 years | 23 years | 12 years | 10 years | 2 years | 11 years | |
| Sex | M | F | F | M | F | M | F | F | |
| Ethnicity | white | African American/white | white | white | white | white | NA | Latino/Hispanic | |
| Growth | |||||||||
| Stature (percentile) | <10th | 99th | >90th | 43rd | 99th | 30th | 1st | 1st | |
| Scoliosis | Y | N | N | N | N | N | NA | N | |
| Comprehensive skills and language | |||||||||
| M-CHAT score | 4 | NA | NA | 15 | 4 | NA | 0 | ||
| Autism diagnosis | Y | N | N | Y | N | Y | NA | Y | |
| Current languagea | 3 | 3 | 2 | 3 | 3 | 0 | 1 | 1 | |
| Age at first word | 11 months | 3 years | ~2 years | 2.5 years | 2 years | NA | NA | 2–3 years | |
| Age using two words together | ~2 years | ~4 years | ~12–13 years | not recalled | NA | NA | |||
| Age at following command | 2 years | NA | NA | has trouble following command | not reported | NA | 1.5 years | ||
| Mobility | |||||||||
| Hypotonia diagnosis | Y | N | N | Y | Y | Y | Y | Y | |
| Independent walking | Y | Y | Y | Y | walking with support | Y | Y | ||
| Age at independent walking | ~2 years | 11 months | 15 months | 1.5 years | 2 years | 1 year | |||
| Sleep/airway | |||||||||
| Sleep apnea | N | Y | N | N | N | N | |||
| Using breathing support | N | Y (CPAP at night) | N | N | N | N | |||
| Neurology | |||||||||
| MRI | normal | NA | not done | abnormal | abnormal | abnormal | abnormal | abnormal | |
| EEG | normal | NA | NA | NA | normal | NA | abnormal | normal | |
| Seizure | Y | Y | NA | Y | Y | Y | Y | N | |
| Age at first seizure | 3 years | NA | 22 years | 2–3 years | 6 years | 3 days | NA | ||
| Ataxia | N | N | N | Y | Y | Y | |||
| Vision | |||||||||
| Wearing glasses or contacts | N | Y | N | N | Y | Y | N | N | |
| Visual acuity | 20/30 | hyperopia, night blindness | normal | NA | NA | hypermetropia | hypermetropia | NA | |
| Strabismus | N | N | N | N | N | Y | Y | N | |
| Dysmorphic features | |||||||||
| Features | coarse facial features | long palpebral fissures, deep-set eyes, hypertelorism, macrocephaly, cleft palate | broad forehead, thin upper lip | macrocephaly (likely familial) | upslanted palpebral fissures, microcephaly, low-set ears | broad forehead, wide nasal bridge, brachycephaly, microtia, clinodactyly 5th finger, mild microcephaly | almond-shaped eyes, thin upper lip, brachycephaly, microcephaly, protuberant ears | upslanting palpebral fissures, microcephaly | |
Of the total of 10 individuals, five joined the XGS Registry and provided all available clinical data (individuals 1, 3, 6, 7, and 10). Partial data were available for three of the additional five known individuals (5, 8, 9). M-CHAT, Modified Checklist for Autism in Toddlers; CPAP, continuous positive airway pressure; MRI, magnetic resonance imaging; EEG, electroencephalogram; M, male; F, female; Y, yes; N, no; NA, not applicable.
a
Current language: 0, no words; 1, <50 words; 2, no sentence but >50 words; and 3, full sentence >200 words.