Table 1

Genetic and phenotypical overview of affected individuals with changes in SHROOM4

FamilyFamily AFamily BFamily CFamily D
IndividualIII-1II-3II-1II-1II-2II-4
SexFemaleMaleMaleMaleMaleMale
Chr. position (hg19)chrX:g.50378133chrX:g.50378133chrX:g.50345632Xp11.23p11.22Xp11.23p11.22Xp11.23p11.22
InheritanceMaternally inherited (skewed X chr)Maternally inheritedMaternally inheritedParents not available for testingParents not available for testingMaternally inherited
Nucleotide changeNM_020717.4:
c.940G>A
NM_020717.4:
c.940G>A
NM_020717.4:
c.3942+1G>A
TypeDeletionDeletionDeletion
Amino acid changep.(Glu314Lys)p.(Glu314Lys)p.?Minimal region affectedchrX:g.49,369,600–50,447,320chrX:g.49,369,600–50,447,320chrX:g.49,375,617–52,838,206
CADD20.520.5NASize1.07 Mb1.07 Mb3.46 Mb
gnomAD allele frequencies (hom/hemi/het/wt)0/0/1/178,7000/0/1/178,700Not reported
Renal and GUUnilateral renal agenesisUnilateral renal agenesisRenal dysplasia and micropenisPUV, cryptorchidism, proteinuria, hypercalciuria and nephrocalcinosis (Dent’s disease)PUV, proteinuria and nephrocalcinosis (Dent’s disease)PUV, bilateral hydronephrosis, renal cortical microcyst, micropenis, cryptorchidism, proteinuria and hypercalciuria (Dent’s disease)
Neurological developmentHypotoniaDD and intellectual disabilityDD, delayed speech and intraventricular bleedingDD, increased muscular tone of lower limbs and epilepsy
GastrointestinalEA with fistula (Vogt type 3b)EA with fistula (Vogt type 3b)Gastric reflux and failure to thriveFailure to thriveFailure to thrive
AnorectalARM with vestibular fistulaARM
CardiacTetralogy of FallotASD and persistent foramen ovale
SkeletalAplasia of right radius bone and left preaxial polydactylyClinodactyly of the fifth finger and equinovarusShort statureShort stature and extremeties
Craniofacial featuresOverfolded helix, depressed nasal bridge, highly arched eyebrow, hypertelorism, micrognathia and posteriorly rotated earsProminent frontal tumours, depressed nasal bridge, hypertelorism, high arched palate and retinal thinningProtruding eyes
Skin and hairMongolian blue spot and single transverse palmar creasesAtopic skin, oedema of the dorsal parts of the feet and lower legs, and periodic red colour of oedematous skinSingle transverse palmar crease
EndocrineHypothyreosis
ImmuneLow C3/C4 and low immunoglobulinsLow C3/C4 and low immunoglobulins
ElectrolytesHypomagnesaemia, hyponatraemia, hypophosphataemia, hypokalaemia, hypokalcaemia and hypochloremiaHypophosphataemia
OtherSingle umbilical artery, nuchal cord and sacral dimpleFanconi syndrome, suspected shaken baby syndrome with subdural hygroma and retinal bleedingRetinitis pigmentosa, omphalocele and inguinal hernia
  • ARM, anorectal malformation; ASD, atrial septal defect; CADD, Combined Annotation Dependent Depletion; chr, chromosome; DD, developmental delay; EA, oesophageal atresia; GU, genitourinary; hemi, hemizygous; het, heterozygous; hom, homozygous; Mb, megabase; NA, not applicable; PUV, posterior urethral valve; wt, wild type.