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Table 1 Clinical characteristics of male FLNA mutation-positive survivors with PVNH and/or EDS-like connective tissue disease

From: FLNA mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature

Mutation (AA)

Age

Age of death

PVNH

Other neurological findings

Aortic dilatation

Other cardiac involvement

Skeletal findings

Skin findings

Gastro-intestinal involvement

Other

Reference

1

p.Ala39Glu

37y

ND

Yes

Transient neonatal convulsions

Mega cisterna magna

No

MVP with mild MR

TAV with mild AR

No

No

ND

Bilateral epicanthic folds

Telecanthus

Anteverted nared

Anteverted helices

[11]

2

p.Leu80Val

5y

ND

Yes

ND

No

MVP with MR

TVP with TR

Bilateral hip dislocation

Joint hypermobility

Brachydactyly

Genu recurvatum

Skin laxity

Excess skin folds over the fingers

ND

Low set, posteriorly rotated ears

Telecanthus

Epicanthal folds

Periorbital fullness

Infraorbital creases

This report

3

p.Met102Val

3y

ND

Yes

Cerebellar hypoplasia Mildly delayed milestones

No

PDA

ND

ND

ND

Cryptorchidism

[47]

4

p.Ile119Asn

ND

57y

Yes

Mega cisterna magna

Yes (60 mm)

MVP with MR

ND

ND

ND

Thrombopenia

[11]

5

p.Lys127Asn

15y

ND

Yes

Mega cisterna magna

Yes (31 mm)

Mild MVP

Thick MV

Joint hypermobility (8/9)

Mild pectus carinatumScoliosis

Soft, mildly hyperelastic skin Umbilical hernia

ND

ND

[43]

6

p.Ile129Met

1d

ND

Yes

ND

No

Dysplastic MV and TV

ND

Skin laxity

ND

High arched palate

[43]

7

p.Ser149Phe

38y

ND

Yes

Complex partial and generalized seizures

No

AR

ND

ND

ND

ND

[47]

8

p.Arg285Cys

10y

ND

Yes

Seizures

No

MVP, small ASD

Joint hypermobility (6/9)

Thin,translucent, elastic skin Supraumbilical hernia

ND

High arched palate

[43]

9

p.Lys331* (mosaic)

1d

ND

Yes

Cerebral vasculature dysplasia

Corpus callosum hypoplasia

No

PDA, VSD

ND

ND

Intestinal pseudo-obstruction (IPO)

Malrotation

Short gut syndrome with dilated small intestine

Bifid uvula

Persistent Thrombocytopenia

[10]

10

p.Gly475*

17y

ND

Yes

ND

ND

ND

ND

ND

ND

ND

[7]

11

c.1692-2A > G (mosaic)

49y

ND

Yes

Cerebellar hypoplasia

Partial complex and generalized seizures

Yes

AV replacement at 26y

Pes cavus

ND

ND

Bifid epiglottis

[47]

12

p.Phe611_Gly615del

18y

50y

ND*

Spinal osteo-arthritis

Muscle hypotonia

No

Severe polyvalvular heart dysplasia

Dilatation of both atria

Chronic heart failure

Joint hypermobility (8/9)

Scoliosis

Genua valga, Bilateral varus deformity

Soft and doughy skin

Skin laxity

Atrophic scar

Prominent veins

ND

Dysmorphic facial features

[20]

13

p.Gly641Gly

1d

ND

Yes

ND

No

Septal defect

PVP

Dysplastic TV

Talipes equinovarus

Inguinal hernia

Severe constipation

Malrotation

Hypertelorism

Downslanting palpebral fissures

Low set, posteriorly rotated ears

[12]

14

p.Leu656Phe

ND

ND

Yes

Seizures

ND

ND

ND

ND

ND

ND

[21]

15

p.Ala1833_Ser1835delinsAsp

1d

2 m

Yes

Corpus callosum hypoplasia

Cervical syringomyelia

Yes

Dysplastic aorta, MV and TV

ASD, small VSD, PDA

Tortuous supra-aortic vessels

Pulmonary hypertension with heart failure

Joint hypermobility

Skin laxity

Malrotation (autopsy)

ND

[43]

16

p.Gly1896Arg (mosaic)

57y

ND

Yes

Seizures

Mega cisterna magna

No

ND

ND

ND

ND

Progressive obstructive lung disease

[27]

17a

p.Glu2142AlafsTer22

19y

ND

No

No

Yes

Severe MR with MVP

Moderate AR

Dilatation of the bilateral pulmonary arteries

Pectus excavatum

Bilateral inguinal hernias

Thin skin

Intestinal malrotation

CIPO

Crohn’s disease

Thrombocytopenia

[34]

17b

 

11y

ND

No

No

No

Moderate MR with MVP

ASD

No

Bilateral inguinal hernias

Intestinal malrotation

CIPO

Cryptorchidism

 

18

p.Ala2257Pro

16y

ND

Yes

Moderate weakness and atropy of the intrinsic hand muscles and wrist extensors bilaterally Seizures

No

PDA

AV dysfunction

Joint hypermobility (7/9)

Pectus excavatum

Bilateral genu recurvatum

Skin laxity

Malrotation

Short gut syndrome

ND

[42]

19a

p.Tyr2305*

ND

ND

Yes

Seizures

ND

ND

ND

ND

ND

ND

[21, 46]

19b

 

36y

36y

Yes

Seizures

Yes

AR

Left ventricular hypertrophy

Left atrial enlargement

ND

ND

ND

ND

 

20

p.Gln2341*

Prenatally

6w

Yes

Posterior fossa arachnoid cyst

ND

ND

Spina bifida occulta

Proximally placed thumbs

ND

Diaphragmatic defect Displaced stomach and spleen

Short gut syndrome with dilated loops of small intestine

“Square face”, flat philtrum

Wide metopic suture

High-arched palate

[18]

21

p.Ser2352* (mosaic)

38y

ND

Yes

Inward rotation of anterior ventricular horns

Corpus callosum hypoplasia

Mega cisterna magna

ND

ND

Broad and flattened OPD I-like end phalanges of both feet

ND

ND

Retrognathia

Hypertelorism

Low-set ears

[27]

22

p.Pro2554Leu

56y

ND

Yes

ND

ND

ND

ND

ND

ND

ND

[7]

23

p.Gly2593Glu

ND

ND

Yes

Seizures

Migraines

No

ND

Joint hypermobility Tall thin habitus

ND

ND

Left-sided sensorineural hearing loss

Retinal lattice degeneration

High arched palate

[44]

24a

p.Asp2622_Lys2623del

5y

ND

Yes

Corpus callosum hypoplasia

Mega cisterna magna

ND

ND

Scoliosis

Mild platyspondyly Spatulate finger tips

Short, broad phalanges and metacarpus

Skeletal dysplasia of the posterior fossa and frontal sinuses

Delayed bone age

ND

ND

Dysmorphic facial features

[8, 9]

24b

 

Neonatal

ND

Yes

Corpus callosum hypoplasia

Mega cisterna Magna

ND

ND

Mild platyspondyly, Spatulate finger tips

Short broad phalanges and metacarpus

Skeletal dysplasia of the posterior fossa and frontal sinuses

Delayed bone age

ND

Malrotation

Dysmorphic facial features

25

p.Pro2641Ala

p.Tyr2642ThrfsTer63

1d

2y

ND*

Broad interhemispheric fissures and subarchnoid spaces with echogenic parenchyma

Muscle hypoplasia and hypotonia

No

Dysmorphic/elongated cusps TV with TVR

Thinned/elongated cusps MV with MVP, ASD

Dilated pulmonary arteries

Pulmonary hypertension, leading to heart failure and early demise

Joint hypermobility

Pectus excavatum

Translucent skin

Chronic diarrhea

Dysmorphic facial features

Food allergies

Recurrent bronchitis

This report

26a

p.Pro2641Leu

1d

ND

Yes

Enlarged anterior fontanel Ventriculomegaly

Seizures

Mental retardation

No

PDA

ND

ND

ND

Severe bronchodysplasia

[41]

26b

 

1d

8 m

Yes

Enlarged anterior fontanel Ventriculomegaly

Microgyria

Microcephaly

No

PDA

ND

ND

ND

Severe bronchodysplasia resulting in death

27a

p.*2648Serext*101

Neonatal

ND

Yes

Corpus callosum hypoplasia

Retrocerebellar cyst

No

PDA

ND

Inguinal hernia

Pyloric stenosis

Constipation

Malrotation

Short gut syndrome

Dysmorphic facial features

[40, 19]

27b

 

Neonatal

ND

Yes

Mildly delayed motor development – hyptonia

Retrocerebellar cyst

No

Mildly dysplastic MV

PDA

Mild pectus excavatum

ND

Severe constipation

Gastro-intestinal obstruction

Short gut syndrome

Recurrent upper respiratory tract infections

Dysmorphic facial features

27c

 

1d

ND

Yes

Hypoplastic cerebellum and vermis

No

ASD

ND

ND

Short gut syndrome Malrotation

Dysmorphic facial features

  1. AR aortic regurgitation, ASD atrial septal defect, AV aortic valve, MVR: mitral valve regurgitation, MR mitral regurgitation, MV mitral valve, MVP mitral valve prolapse, ND not described, PDA patent ductus arteriosus, PVP pulmonary valve prolapse, TAV tricuspid aortic valve, TV tricuspid valve, TVP tricuspid valve prolapse, TVR tricuspid valve regurgitation, VSD ventricular septal defect, CIPO chronic intestinal pseudo-obstruction. Patient 23a is brother of patient 23b