Table 1

Comparison of clinical features in patients with VPS35L, CCDC22 and WASHC5 pathogenic variantstable 1

VPS35L CCDC22 WASHC5
Pt-1A
(previous
case)
Pt-1B
(previous
case)
Pt-2
(present
case)
Pt-3
(present
case)
Pt-4
(present
case)
Gender/AgeFemale/0 year* Male/7 yearsMale/31 yearsMale/8 yearsMale/32 years
Intellectual disabilityNASevereMildMildProfoundNormal to profound10/10
Postnatal growth retardationNA−6.2 SD−2.1 SD−2.9 SD−6.5 SD−3.7 SD to normalND
Brain MRI findings
 Cerebellar dysplasia+++3/85/10
 Cortical dysplasia+ (PNH)+ (PNH)+ (Enlarged ventricles)1/10
 Calcification+ (Falx cerebri)+ (Cerebellum and BG)
Craniofacial dysmorphism
 Relative macrocephaly++++2/810/10
 Arched eyebrows+++++5/10
 Thin upper lips++++3/85/10
 Macrodontia++NDND
Limb abnormalities
 Brachymelia/Brachydactyly++++ND2/10
 Reduced distal creases++++1/81/10
Congenital heart diseasesAVSDVSD3/86/10
Ophthalmological changes
 Glaucoma+++1/8ND
 Coloboma+ (Choroidal coloboma)+ (Choroidal coloboma)ND3/10
 Microphthalmus+ (Optic nerve atrophy)NDND
ProteinuriaNA+++NANDND
DyslipidaemiaNA+++NA2/8ND
Increased transaminasesNA+++NANDND
HypogammaglobulinaemiaNA+++NANDND
Generalised hypotoniaNA++++3/8ND
OthersCDPEpilepsy, CDP, hypoplasia of vertebral body and breast boneIntestinal lymphangiectasia
Hearing impairment
Congenital scalp defect, cutis marmorataHearing impairment, ocular albinism, large anterior fontanelleHypoplastic lungHydrocephaly
Variant 1†c.2755G>A; p.A919Tc.2755G>A; p.A919Tc.1650+2T>Ac.3057del; p.M1020Wfs*2c.2627C>T; p.P876L
Variant 2†c.1097dup; p.C366Wfs*28c.1097dup; p.C366Wfs*28c.2988_2990del;
p.N996del
c.1577del;
p.A526_K550del‡‡
c.2627C>T; p.P876L
  • *Sudden death at infantile period.

  • †Transcript, NM_020314.5.

  • ‡p.A526_K550del was experimentally confirmed while p.A526Vfs*14 was estimated in silico.

  • §

  • –, not present; +, present; AVSD, atrioventricular defect; BG, basal ganglia; CDP, chondrodysplasia punctata; NA, information not available; ND, information not described; PNH, periventricular nodular heterotopia; Pt, patient; VSD, ventricular septal defect.