HIST1H1E Clinical Phenotype
Individuals with HIST1H1E mutations had similar facial appearance in childhood with full cheeks, high hairline, and telecanthus (Figures 2B–2D). Height, head circumference, and degree of intellectual disability were variable, as were the additional clinical features. It is currently unclear whether these additional features are HIST1H1E associations or coincidental findings. Individual case descriptions are below.
COG0405, a female individual, was born at term with a weight of 3.58 kg (+0.1 SD) and a length of 53 cm (+1.5 SD). She was floppy in the neonatal period. A brain MRI scan at 4 months demonstrated mild ventricular dilatation but no other abnormalities. Her bone age at chronological age of 7 months was advanced to 18–24 months. By 19 months, her length was 87 cm (+2.0 SD) with a weight of 13.4 kg (+1.8 SD) and she had developed a strabismus. At 13 years of age, the individual was noted to have normal growth with a height of 150.8 cm (−0.6 SD), a head circumference of 55.8 cm (−0.5 SD), and a weight of 48.85 kg (+0.4 SD). She has developed a severe kyphoscoliosis for which she required surgery and has a mild intellectual disability.
COG0412, a male individual, was born at 1 week after term following an uncomplicated pregnancy and delivery. He weighed 4.75 kg (+2.4 SD). In the neonatal period he was noted to be floppy; he had poor feeding and undescended testes. At 1.5 years he was very tall at 105 cm (+8.3 SD) with a weight of 18.8 kg (+4.6 SD) and a head circumference of 52.5 cm (+2.6 SD). He was reported to have multiple nevi and redundant skin on the palms of his hands. He had a moderate intellectual disability and no behavioral issues at that time. When he was reviewed at 15.5 years, he was no longer tall with a height of 166.5 cm (−0.6 SD). His head circumference was 58.7 cm (+1.4 SD). By this age he had developed an anxiety disorder that was refractory to medical treatment. He had also developed phobias. In addition, he had major dental problems with crumbling teeth and he had dry, flaky nails.
COG0552, a female individual, was born at term with a weight of 4.79 kg (+2.5 SD) and length of 57 cm (+3.6 SD). She was floppy in the neonatal period with poor feeding. She developed no new medical problems in childhood. At the age of 4.2 years she was reported to be delayed in her development. She had a height of 108 cm (+1.2 SD), head circumference of 55 cm (+3.2 SD), and weight of 24 kg (+2.7 SD).
COG1739, a female individual, was initially thought clinically to have Weaver syndrome. She was born at 37 weeks after an uncomplicated pregnancy and labor with a weight of 3.25 kg (+0.8 SD), length of 49 cm (+0.7 SD), and head circumference of 37 cm (+3.3 SD). She was hypoglycemic and hypertonic in the neonatal period, and was also noted to have camptodactyly. At 1.9 years she was diagnosed with a moderate intellectual disability and had a height of 85 cm (mean), head circumference of 51 cm (+1.8 SD), and weight of 12 kg (−0.3 SD).
COG1832, a male individual, was born at 1 week after term weighing 3.74 kg (+0.4 SD). The pregnancy had been complicated by exposure to chicken pox. At birth, COG1832 was noted to have talipes equinovarus and later in the neonatal period was diagnosed with delayed visual maturation. A brain MRI scan showed a slender corpus callosum and unusual ventricular outline, possibly indicative of a periventricular leukomalacia. At 8.5 years, height was 133.2 cm (+0.5 SD) with a weight of 33 kg (+1.2 SD). The head circumference at 6.3 years was 59 cm (+3.7 SD). He has limited speech but with verbal comprehension markedly ahead of this ability to express himself. He has left amblyopia and astigmatism. His hearing is normal. He suffers from constipation. At times his behavior is challenging.