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Gaze palsy, familial horizontal, with progressive scoliosis 1(HGPPS1)

MedGen UID:
1647423
Concept ID:
C4551964
Disease or Syndrome
Synonym: HGPPS1
 
Gene (location): ROBO3 (11q24.2)
 
Monarch Initiative: MONDO:0020790
OMIM®: 607313

Definition

Familial horizontal gaze palsy with progressive scoliosis-1 (HGPPS1) is an autosomal recessive neurologic disorder characterized by eye movement abnormalities apparent from birth and childhood-onset progressive scoliosis. These features are associated with a developmental malformation of the brainstem including hypoplasia of the pons and cerebellar peduncles and defective decussation of certain neuronal systems. Cognitive function is normal (summary by Bosley et al., 2005). Genetic Heterogeneity of Familial Horizontal Gaze Palsy with Progressive Scoliosis See also HGPPS2 (617542), caused by mutation in the DCC gene (120470) on chromosome 18q21. [from OMIM]

Additional description

From MedlinePlus Genetics
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects vision and also causes an abnormal curvature of the spine (scoliosis). People with this condition are unable to move their eyes side-to-side (horizontally). As a result, affected individuals must turn their head instead of moving their eyes to track moving objects. Up-and-down (vertical) eye movements are typically normal.

In people with HGPPS, an abnormal side-to-side curvature of the spine develops in infancy or childhood. It tends to be moderate to severe and worsens over time. Because the abnormal spine position can be painful and interfere with movement, it is often treated with surgery early in life.  https://medlineplus.gov/genetics/condition/horizontal-gaze-palsy-with-progressive-scoliosis

Clinical features

From HPO
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hypoplasia of the pons
MedGen UID:
341246
Concept ID:
C1848529
Finding
Underdevelopment of the pons.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Plagiocephaly
MedGen UID:
78562
Concept ID:
C0265529
Congenital Abnormality
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Thoracolumbar scoliosis
MedGen UID:
196671
Concept ID:
C0749379
Anatomical Abnormality
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Impaired ocular abduction
MedGen UID:
375894
Concept ID:
C1846462
Finding
An impaired ability of the eye to move in the outward direction (towards the side of the head).
Hyperopic astigmatism
MedGen UID:
376146
Concept ID:
C1847524
Disease or Syndrome
A form of astigmatism in which one meridian is hyperopic while the one at a right angle to it has no refractive error.
Progressive ophthalmoplegia
MedGen UID:
384479
Concept ID:
C2062713
Disease or Syndrome
Horizontal supranuclear gaze palsy
MedGen UID:
870350
Concept ID:
C4024794
Disease or Syndrome
A supranuclear gaze palsy is an inability to look in a horizontal direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.

Recent clinical studies

Etiology

Günbey C, Çavdarlı B, Göçmen R, Yazıcı M, Temuçin ÇM, Özdemir Ö, Çırak S, Haliloğlu G
Ann Clin Transl Neurol 2024 Aug;11(8):2088-2099. Epub 2024 Jun 21 doi: 10.1002/acn3.52129. PMID: 39030736Free PMC Article

Diagnosis

Günbey C, Çavdarlı B, Göçmen R, Yazıcı M, Temuçin ÇM, Özdemir Ö, Çırak S, Haliloğlu G
Ann Clin Transl Neurol 2024 Aug;11(8):2088-2099. Epub 2024 Jun 21 doi: 10.1002/acn3.52129. PMID: 39030736Free PMC Article
Ucan B, Kaynak Sahap S, Bako D, Tıras ST, Ceylaner S, Fitöz S
Klin Padiatr 2022 Jan;234(1):52-55. Epub 2021 Jul 20 doi: 10.1055/a-1478-4528. PMID: 34284498

Prognosis

Günbey C, Çavdarlı B, Göçmen R, Yazıcı M, Temuçin ÇM, Özdemir Ö, Çırak S, Haliloğlu G
Ann Clin Transl Neurol 2024 Aug;11(8):2088-2099. Epub 2024 Jun 21 doi: 10.1002/acn3.52129. PMID: 39030736Free PMC Article
Zaka A, Shahzad S, Rao HZ, Hashim Y, Basit S
Am J Med Genet A 2021 Feb;185(2):355-361. Epub 2020 Nov 3 doi: 10.1002/ajmg.a.61952. PMID: 33141514

Clinical prediction guides

Zaka A, Shahzad S, Rao HZ, Hashim Y, Basit S
Am J Med Genet A 2021 Feb;185(2):355-361. Epub 2020 Nov 3 doi: 10.1002/ajmg.a.61952. PMID: 33141514

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