Table 1.
Detailed phenotypic manifestations of families with ID syndromes.
| Family/Disease | Approaches | Gene (mutation) | Cognition | Movement | Seizure | Consanguinity | Other |
|---|---|---|---|---|---|---|---|
|
ID-Fam01 (Sanfilippo syndrome) |
HM & WGS |
Pts. II-1, - 2, -3 NAGLU (p.D312N) |
Severe ID | No movement abnormalities | yes | Yes | — |
|
ID-Fam02 (Renal glycosuria and ID) |
HM & WGS |
Pts. II-1, -2, -3 SLC5A2 (p.C361Y) |
Moderate ID and dysarthria | Truncal ataxia and titubation, impaired finger to nose exam, increased tone in lower limbs and spasticity, increased deep tendon reflexes, upward plantar reflexes, and spastic-ataxic gait | Yes | Yes | Glucosuria |
|
ID-Fam03 (Familial hypomagnesemia) |
HM & WGS |
Pt. II-1 POLR3B (p.V609M, p.V667M) |
ID from childhood and mental regression, anxiety and abnormal social behavioral disorders, pseudobulbar affect, and autistic-like symptoms | Stereotyped abnormal cervical movements, hyperreflexia (DTR: + 3), hesitate speech and stuttering, mild spastic muscle tone, babinski sign, terminal dysmetry and abnormal tandem gait, wide base spastic and ataxic gait with flexed arms on elbow and fisting | Yes | Yes | Bilateral cataract, basal ganglia calcification, mild hydrocephaly and generalized and cerebellar atrophy |
|
Pt. II-2 POLR3B (p.V609M, p.V667M) |
ID from childhood and mental regression ADHD, OCD (washing) and aggressive disorders |
Mild Spastic muscle tone, hyperreflexia (DTR: + 3), babinski sign, terminal dysmetry and abnormal tandem gait, wide base spastic and ataxic gait with flexed arms on elbow and fisting | No | Yes | Bilateral cataract, basal ganglia calcification, mild hydrocephaly and generalized and cerebellar atrophy | ||
|
ID-Fam04 (Chorea-acanthocytosis) |
WGS |
Pt. II-1 VPS13A (p.R1922X, p.R1961X) |
Mental regression and impaired recent memory | Oromandibular dyskinesia, choreaic movement of tongue that interfere with eating and speaking, rubber man like body movement and some motor tics, dystonic gait with bilateral foot drop | Yes | Yes | Generalized atrophy in brain MRI |
|
ID-Fam05 (Autism and progressive ID without epilepsy) (3 male patients) |
HM & WGS |
Pts. II-4, -5 SYN1 (p.R420Q) |
ID from early childhood mental regression Autistic features |
No marked rigidity or tremor | No | No | Abnormal eye contact and language problem, sphincter dysfunction, marked generalized frontal atrophy in brain MRI |
|
ID-Fam06 (HSP and mild intellectual disability) |
HM & WGS |
Pt. II-1 SPG11 (p.M245Vfs*2) |
Mild ID | Resting tremor that aggravated with action and intention, severe spastic gait with some knee and ankle contracture, hyperreflexia with bilateral, babinski sign, mild bilateral dysmetry in finger to nose test | No | Yes | Typical thinning of corpus callusom and “ear of the lynx” appearance in anterior, aspect of ventriculs on MRI, bilateral jerk gaze evoked horizontal nystagmus, swan neck deformity in fingers and mild hyper-laxity of phalanx, discoloration of frontal skin to a blue-gray color |
|
Pt. II-2 SPG11 (p.M245Vfs*2) |
Mild ID | Spastic gait with severe hyperreflexia and Babinski sign, mild bilateral dysmetry in finger to nose test | No | Yes |
Discoloration of frontal skin to a blue-gray color Typical thinning of corpus callusom and “ear of the lynx” appearance in anterior aspect of ventriculs on MRI |
||
|
Pt. II-3 SPG11 (p.M245Vfs*2) |
Mild ID | Hyperreflexia and Babinski sign, mild terminal dysmetry in finger to nose test, resting tremor, spastic gait | No | Yes | Hyperlaxity in phalanx with swan neck appearance, blue-gray discoloration of skin (especially frontal), typical thinning of corpus callusom and “ear of the lynx” appearance in anterior aspect of ventriculus on MRI | ||
|
ID-Fam07 (HSP and mild intellectual disability) |
HM & WGS |
Pt. II-1/Pt. II-2 NSL1 (p.R74P) |
Mild ID | Spastic paraparesis with hyperreflexia, Babinski sign and spastic gait | Yes | Yes | gradually decreasing vision |
ADHD: Attention deficit hyperactivity disorder; OCD: Obsessive-compulsive disorder.