Welcome to PhenoDis

Autosomal dominant spastic paraplegia type 9

General Information (adopted from Orphanet):

Synonyms, Signs:	SPG9 Cataracts with motor neuronopathy, short stature, and skeletal abnormalities Spastic paraparesis - amyopathy - cataracts - gastroesophageal reflux Spastic paraparesis with amyopathy, cataracts, and gastroesophageal reflux Cataracts motor neuropathy - short stature - skeletal anomalies
Number of Symptoms	30
OrphanetNr:	100990
OMIM Id:	601162
ICD-10:	G11.4
UMLs:	C1832669
MeSH:	C536868
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	1 family [Orphanet]
Inheritance:	Autosomal dominant 9973297 [IBIS]
Age of onset:	Childhood Adult 9973297 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases:

Autosomal dominant complex spastic paraplegia
-Rare genetic disease
-Rare neurologic disease

Comment:

ALDH18A1 (= GSAS; P5CS; PYCS; SPG9; ADCL3; SPG9A; SPG9B; ARCL3A) gene mutations cause dominant spastic paraplegia SPG9.

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Pubmed	Source	DB Freq
1	(HPO:0002013)	Vomiting	19390613	IBIS	191 / 7739
2	(HPO:0000518)	Cataract	19007737	IBIS	454 / 7739
3	(HPO:0004322)	Short stature	8779323	IBIS	1232 / 7739
4	(HPO:0003202)	Skeletal muscle atrophy	9973297	IBIS	281 / 7739
5	(HPO:0003700)	Generalized amyotrophy	9973297	IBIS	39 / 7739
6	(HPO:0002460)	Distal muscle weakness	8779323	IBIS	122 / 7739
7	(HPO:0007340)	Lower limb muscle weakness	8779323	IBIS	61 / 7739
8	(HPO:0003701)	Proximal muscle weakness	8779323	IBIS	105 / 7739
9	(HPO:0002127)	Abnormal upper motor neuron morphology	8779323	IBIS	15 / 7739
10	(MedDRA:10007697)	Carpal tunnel syndrome	8779323	IBIS	16 / 7739
11	(HPO:0007002)	Motor axonal neuropathy	9973297	IBIS	17 / 7739
12	(HPO:0007178)	Motor polyneuropathy	9973297	IBIS	31 / 7739
13	(HPO:0000763)	Sensory neuropathy	9973297	IBIS	78 / 7739
14	(HPO:0003487)	Babinski sign	9973297	IBIS	179 / 7739
15	(HPO:0007299)	Dysfunction of lateral corticospinal tracts	8779323	IBIS	1 / 7739
16	(HPO:0001347)	Hyperreflexia	8779323	IBIS	363 / 7739
17	(HPO:0001276)	Hypertonia	8779323	IBIS	317 / 7739
18	(HPO:0001258)	Spastic paraplegia	26297558	IBIS	97 / 7739
19	(HPO:0003470)	Paralysis	19390613	IBIS	11 / 7739
20	(HPO:0001328)	Specific learning disability	8779323	IBIS	114 / 7739
21	(HPO:0001263)	Global developmental delay	8779323	IBIS	853 / 7739
22	(HPO:0001288)	Gait disturbance	9973297	IBIS	318 / 7739
23	(MedDRA:10033985)	Paresis	19390613	IBIS	2 / 7739
24	(HPO:0001760)	Abnormality of the foot	19390613	IBIS	96 / 7739
25	(HPO:0001761)	Pes cavus	9973297	IBIS	225 / 7739
26	(HPO:0001498)	Carpal bone hypoplasia	8779323	IBIS	17 / 7739
27	(HPO:0002750)	Delayed skeletal maturation	8779323	IBIS	250 / 7739
28	(HPO:0002020)	Gastroesophageal reflux	19007737	IBIS	101 / 7739
29	(HPO:0002036)	Hiatus hernia	8779323	IBIS	24 / 7739
30	(HPO:0000924)	Abnormality of the skeletal system	19007737	IBIS	114 / 7739

Associated genes:

ALDH18A1;

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Slavotinek et al. (1996) presented a 4-generation family in which affected individuals had cataracts, a motor neuronopathy with upper motor neuron signs, short stature, developmental delay, and skeletal abnormalities. In the affected females, weakness developed during pregnancy and ... Slavotinek et al. (1996) presented a 4-generation family in which affected individuals had cataracts, a motor neuronopathy with upper motor neuron signs, short stature, developmental delay, and skeletal abnormalities. In the affected females, weakness developed during pregnancy and resolved after delivery. The condition was inherited in an autosomal dominant manner with an instance of male-to-male transmission in the first 2 generations. Bilateral lamellar cataracts were noted in the first year or so of life and lensectomy was performed early. Delayed bone age, shallow acetabulum, and small carpal bones were described. Poor muscle mass, weakness of the distal muscle groups in the arms and the proximal muscle groups in the lower limbs was observed. Dysplastic base of the skull was also mentioned as a feature in a woman who developed weakness and wasting in the small muscles of her hands at 7 months of pregnancy. With the proband a benign form of muscular atrophy was considered but abandoned when the weakness improved and the patient recovered with no weakness and normal reflexes at 6 months after delivery. A similar illness was noted during her second pregnancy. The products of both the pregnancies were affected. Anticipation was thought to occur in this family. The proband had neurologic signs in his first year of life, whereas his mother's symptoms were first apparent at age 22 years, and in the preceding generation, an affected member presented with weak legs at age 37 years. Several of the affected members were under the third centile for height; the mother of the proband was 147.5 cm tall at the age of 32 years and had a short fifth finger with clinodactyly. The disorder described here and designated SPG9 is a complicated form of spastic paraparesis. Seri et al. (1999) reported ocular abnormalities occurred in all affected individuals in a large Italian pedigree, with the exception of one who presented with myopia and chorioretinal dystrophy. Furthermore, all subjects presented with persistent vomiting, and in 2 of them, gastroesophageal reflux was diagnosed. The presence of hiatal hernia was ascertained by esophageal endoscopy in 4 affected subjects. Spastic paraparesis showed incomplete penetrance and/or variable expressivity. Pes cavus and the Babinski sign, along with different degrees of muscle wasting in the hands and forelegs, were present in some subjects. Electrophysiologic studies confirmed involvement of the central motor pathways and revealed a peripheral neuropathy that involved mainly the motor axons. Spastic paraparesis appeared in the first and in the third decade of life in different members of the family, with some indications of anticipation. One patient presented with difficulties with ambulation in later adulthood only. His daughter manifested muscle weakness and difficulties walking during pregnancy, at age 25 years. By the age of 35 years, she had severe impairment of ambulation. Her son showed gait disturbances and pes cavus at the age of 4 years.

Symptoms & Signs

	Field	Query
	Disease
	Symptom