Differential Diagnosis
The phenotypic features associated with SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) are not sufficiently specific to diagnose this condition clinically; all disorders with intellectual disability and/or seizures without other distinctive findings should be considered in the differential diagnosis. See OMIM Phenotypic Series: • Autosomal Dominant Intellectual Developmental Disorder • Autosomal Recessive Intellectual Developmental Disorder • Nonsyndromic X-Linked Intellectual Developmental Disorder • Syndromic X-Linked Intellectual Developmental Disorder • Developmental and Epileptic Encephalopathy SLC6A1-NDD shares phenotypic similarities, including developmental delay, epilepsy, and autism spectrum disorder, with the disorders listed in . In particular, Rett syndrome may be considered in individuals with developmental regression, and Angelman syndrome may be considered in those with intermittent rhythmic delta activity on their EEG. Finally, sodium channelopathies (SCN1A, SCN2A, SCN8A) and GABAA receptor-related epilepsies (GABRA1, GABRB2, GABRB3, GABRG2) also have a broad phenotypic spectrum that includes epilepsy, developmental delay, and autism spectrum disorder. Table 3. Selected Genes of Interest in the Differential Diagnosis of SLC6A1-Related Neurodevelopmental Disorder
Gene(s) | Disorder | MOI | Clinical Characteristics | Comment |
|---|
GABRG2 | GABAA receptor-related epilepsies (OMIM 137160, 600232, 137192, 137164) | AD | Generalized epilepsy w/or w/o NDD. Some individuals have ASD, behavioral issues, or movement disorders. EEGs can have variable findings ranging from normal to abnormal w/focal or generalized spike-wave discharges, hypsarrhythmia, or burst-suppression pattern. Fever-related seizures are common. | Persons w/SLC6A1-NDD are unlikely to have hypsarrhythmia or burst-suppression pattern on EEG may be more likely to have NDD. |
MECP2 | Rett syndrome (See MECP2 Disorders.) | XL | Progressive NDD primarily affecting females characterized by apparently normal psychomotor development in 1st 6-18 mos of life, followed by short period of developmental stagnation, then rapid regression in language motor skills, followed by long-term stability. | Persons w/Rett syndrome typically have more severe DD/ID than those w/SLC6A1-NDD. SCN1A SCN2A |
SCN8A | Sodium channelopathies (See, e.g., SCN1A Seizure Disorders and SCN8A-Related Epilepsy w/Encephalopathy.) | AD | Epilepsy, ASD, DD. Seizures are often exacerbated by heat persons are prone to status epilepticus. May have encephalopathic features on EEG consistent w/DEE or LGS. Seizure onset is typically w/in 1st yr of life, there is risk of SUDEP. | — |
Source: GeneReviews — "SLC6A1-Related Neurodevelopmental Disorder"
