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Squalene synthase deficiency(SQSD)

MedGen UID:
1648421
Concept ID:
C4748427
Disease or Syndrome
Synonym: NEURODEVELOPMENTAL DISORDER WITH LOW CHOLESTEROL AND ABNORMAL URINE ORGANIC ACIDS
 
Gene (location): FDFT1 (8p23.1)
 
Monarch Initiative: MONDO:0032566
OMIM®: 618156

Disease characteristics

Excerpted from the GeneReview: Squalene Synthase Deficiency
Squalene synthase deficiency (SQSD) is a rare inborn error of cholesterol biosynthesis with multisystem clinical manifestations similar to Smith-Lemli-Optiz syndrome. Key clinical features include facial dysmorphism, a generalized seizure disorder presenting in the neonatal period, nonspecific structural brain malformations, cortical visual impairment, optic nerve hypoplasia, profound developmental delay / intellectual disability, dry skin with photosensitivity, and genital malformations in males. [from GeneReviews]
Authors:
David Coman  |  Lisenka Vissers  |  Hans Waterham, et. al.   view full author information

Additional description

From OMIM
Squalene synthase deficiency (SQSD) is an autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, and facial dysmorphisms, as well as low total and LDL-cholesterol and abnormal urine organic acids (Coman et al., 2018).  http://www.omim.org/entry/618156

Clinical features

From HPO
Bilateral cryptorchidism
MedGen UID:
96568
Concept ID:
C0431663
Congenital Abnormality
Absence of both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Elevated urine mesaconic acid level
MedGen UID:
1863641
Concept ID:
C5937234
Finding
The amount of mesaconic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Elevated urine 3-methyladipic acid level
MedGen UID:
1863947
Concept ID:
C5937235
Finding
The amount of 3-methyladipic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Elevated urinary mevalonate lactone level
MedGen UID:
1863443
Concept ID:
C5937415
Finding
The amount of mevalonate lactone in the urine, normalized for urine concentration, is above the upper limit of normal.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
2-3 toe syndactyly
MedGen UID:
1645640
Concept ID:
C4551570
Congenital Abnormality
Syndactyly with fusion of toes two and three.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Gastrostomy tube feeding in infancy
MedGen UID:
892362
Concept ID:
C4023342
Finding
Feeding problem necessitating gastrostomy tube feeding.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Polymicrogyria
MedGen UID:
78605
Concept ID:
C0266464
Congenital Abnormality
Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Elevated methylhex-dienedioic level by MRS
MedGen UID:
1863563
Concept ID:
C5937609
Finding
An increase in the level of 3-methylhex-2,4-dienedioic acid or 3-methylhex-3,4-dienedioic acid in the brain identified by magnetic resonance spectroscopy (MRS).
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Slender long bone
MedGen UID:
331446
Concept ID:
C1833144
Finding
Reduced diameter of a long bone.
Hypocholesterolemia
MedGen UID:
57479
Concept ID:
C0151718
Disease or Syndrome
An decreased concentration of cholesterol in the blood.
Decreased LDL cholesterol concentration
MedGen UID:
776554
Concept ID:
C0853085
Finding
An decreased concentration of low-density lipoprotein cholesterol in the blood.
Increased circulating farnesol concentration
MedGen UID:
1756698
Concept ID:
C5421597
Finding
An elevated level of farnesol in the blood circulation.
Elevated circulating methylsuccinic acid concentration
MedGen UID:
1753480
Concept ID:
C5421640
Finding
Increased concentration of methylsuccinic acid in the blood circulation.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Abnormality of hair pigmentation
MedGen UID:
869743
Concept ID:
C4024172
Finding
An abnormality of hair pigmentation (color).
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

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