Table 1 Clinical features of five pediatric patients with dual genetic diseases
Clinical features | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 |
|---|---|---|---|---|---|
Gender | M | F | M | F | M |
Age at diagnosis | 7 years | 3 months | 10 years | 3 years | 1 year and 8 months |
Genetic diseases | Angelman syndrome | Citrin deficiency | Homocysteinemia type 2 | Isolated methylmalonic acidemia | Isolated methylmalonic acidemia |
Krabbe disease | Kabuki syndrome | Copy number variant | Niemann-Pick disease type B | 21-hydroxylase deficiency | |
Neurology | General developmental delay, increased muscle tension, poor grasping | Developmental delay, increased muscular tension | Severe mental delay, seizures, dysarthria, increased muscle tension | General developmental delay | Psychomotor retardation |
Skeletal and muscle | Thumb buckling | - | Dorsiflexion restriction and varus of both feet | - | - |
Digestive | - | Liver dysfunction | - | Abnormal liver function | Feeding difficulties, diarrhea, metabolic acidosis |
Appearance | - | Long cleft on the eyelid, elongated lateral canthus, heavy eyebrows, cleft palate | - | - | - |
Endocrine | - | - | - | - | Precocious puberty |
Other features | Irritability and a distinctive giggle | - | - | - | - |
Genes with pathogenic variants | |||||
Gene A | 15q11.2q13.1del | KMT2D | 16p11.2del | MMUT | MMUT |
Gene B | GALC | SLC25A13 | MTHFR | SMPD1 | CYP21A2 |
Modes of inheritance (Gene A + Gene B) | AD + AR | AD + AR | AD + AR | AR + AR | AR + AR |