snyder-robinson syndrome a 46 year odyssey

Snyder-Robinson Syndrome A 46 Year Odyssey

Arlington, VA

July 16, 2015

Clinical Pediatrics 8:669, 1969

Russell Snyder Arthur Robinson

1969 - Snyder-Robinson publication

1989 - NIH funding to GGC-Miami for XLID research

Aarskog S.

Mohr-Tranebjaerg S.

Hydrocephaly-MASA spectrum

Carpenter-Waziri S.

Snyder-Robinson S.

Allan-Herndon S.

Christianson, Angelman-like S.

Renpenning S.

Carpenter S.

Miles-Carpenter S.

Golabi-Ito-Hall S.

Porteous S.

Chudley-Lowry S.

Holmes-Gang S.

XLID-arch fingerprints-hypotonia S.

22.3

22.1

21.1

21.3

13

25

28

11 12

26

27

24

23

22.3

22.2

22.1

21.2

11.4

11.3

11.1

21.1

21.2

21.3

22.2

11.23

11.22

11.21

Lujan S.

Juberg-Marsidi S.

(ATRX)

(HUWE1) (ZC4H2) (PQBP1)

(MCT8) (MED12)

(SMS)

(SLC9A6)

(AP1S2)

(FGDY)

(TIMM8A)

(L1CAM)

(UPF3B)

XLID-hypogonadism-tremor (CUL4B)

Coffin-Lowry (RPSKA3, RSK2)

Aarskog (FGDY)

Telecanthus-hypospadias (MID1)

Pyruvate dehydrogenase deficiency (PDHA1) Glycerol kinase deficiency (GKD)

Duchenne muscular dystrophy (DMD) Ornithine transcarbamoylase deficiency (OTC)

Monoamine oxidase-A deficiency (MAOA) Norrie (NDP)

Pelizaeus-Merzbacher (PLP) Mohr-Tranebjaerg (TIMM8A, DDP)

Lissencephaly, X-linked (DCX)

Lowe (OCRL1) Simpson-Golabi-Behmel (GPC3)

Lesch-Nyhan (HPRT) Fragile XA (FMR1) Mucopolysaccharidosis IIA (IDS)

Myotubular myopathy (MTM1)

Adrenoleukodystrophy (ABCD1)

Hydrocephaly-MASA spectrum (L1CAM)

Rett, PPM-X (MECP2)*

Incontinentia pigmenti (IKBKG, NEMO) Dyskeratosis congenita (DKC1)

-Thalassemia Intellectual Disability XLID-hypotonic facies, Carpenter-Waziri,

Holmes-Gang, Chudley-Lowry, XLID-arch

fingerprints-hypotonia, Smith-Fineman-Myers(?)

(ATRX, XNP,

XH2)

XLID-optic atrophy (AGTR2)

Partington, West, Proud, XLAG (ARX)

Börjeson-Forssman-Lehmann (PHF6)

Oral-facial-digital I (OFD1)

Snyder-Robinson (SMS)

XLID-growth hormone deficiency (SOX3)

Periventricular nodular heterotopia, Otopalatodigital I, Otopalatodigital II, Melnick-Needles

(FLNA, FLN1)

Phosphoglycerate kinase deficiency (PGK1) Menkes disease (ATP7A)

XLID-infantile seizures, Rett like (CDKL5, STK9) Nance-Horan (NHS)

XLID-cerebellar dysgenesis (OPHN-1)

XIDE (Renin receptor; ATP6AP2)

Autism (NLGN4)

OFCD, Lenz microphthalmia (BCOR)

XLID-choreoathetosis (HADH2)

Stocco dos Santos (SHROOM4, KIAA1202)

XLID-cleft lip/palate (PHF8)

Epilepsy/macrocephaly (SYN1)

Allan-Herndon (SLC16A2, MCT8)

Creatine transporter deficiency (SLC6A8)

Danon cardiomyopathy (LAMP2)

Arts, PRPP synthetase superactivity (PRPS1)

Cornelia de Lange, X-linked (SMC1L1, SMC1A)

Opitz-Kaveggia FG, Lujan (MED12, HOPA)

MIDAS (HCCS) Turner, XLID-hydrocephaly-

basal ganglia calcification

XLID-nail dystrophy-seizures (UBE2A)

XLID-macrocephaly-large ears (BRWD3)

XLID-macrocephaly-Marfanoid habitus (ZDHHC9)

Christianson, Angelman-like (SLC9A6)

FG/Lujan phenotype (UPF3B)

Graham coloboma (IGBP1)

Autism (RPL10)

XLID-short stature-muscle wasting (NXF5)

Cantagrel spastic paraplegia (KIAA2022)

VACTERL-hydrocephalus (FANCB)

Mitochondrial encephalopathy (NDUFA1)

Chiyonobu XLID (GRIA3)

Renpenning, Sutherland-Haan,

Cerebropalatocardiac (Hamel),

Golabi-Ito-Hall, Porteous (PQBP1)

1 3

2 5

2 8

1 1 1 2

2 6

2 7

2 4

2 3

22.3

22.2

22.1

21.3

21.2

21.1

11.4

11.3

11.1

21.1

21.2

21.3

22.1 22.2 22.3

11.23

11.22 11.21

XLID-hyperekplexia-seizures (ARHGEF9)

Goltz (PORCN)

(AP1S2)

Epilepsy-intellectual disability limited to females (PCDH19)

Ichthyosis follicularis, atrichia, photophobia (MBTPS2)

Microcephaly-pachygyria-dysmorphism (NSDHL)

XLID-macrocephaly-seizures-autism (RAB39B)

XLID-macrocephaly Juberg-Marsidi-Brooks

(HUWE1)

Chaissaing-Lacombe chondrodysplasia (HDAC6)

Martin-Probst (RAB40AL)

XLID-nystagmus-seizures (CASK)

MEHMO (EIF2S3)

N-Alpha acetyltransferase deficiency (NAA10)

TARP (RBM10)

Wilson-Turner (LAS1L)

Cornelia de Lange, X-linked (HDAC8)

XLID-Rolandic seizures (SRPX2)

XLID-cardiomegaly-seizures (CLIC2)

XLID-microcephaly-seizures (CNKSR2)

XLID-aggression (EBP)

Cardiofacioskeletal (CCDC22)

Charcot-Marie-Tooth, Cowchock variant (AIFM1)

Microcephaly-stereotypies-seizures (IQSEC2)

Wieacker-Wolff,

Miles-Carpenter (ZC4H2)

XLID-microcephaly-dystonia (BCAP31)

X-linked Kabuki (KDM6A)

XLID-iron accumulation (PIGA)

NBIA-XLID (WDR45)

XLID-glycosylation defect (SSR4)

Autism-ID (TMLHE)

XLID-aortic stenosis-hypospadias (ZMYM3)

XLID-coarse facies (RBMX)

XLID-ubiquitin peptidase deficiency (USP27X)

XLID-facial dysmorphism (KLHL15)

XLID-aphasia-seizures (FRMPD4)

1991 - Visits with Gallagher/Leis/Marchetti Families

1991 Minnesota (MG, DG, CG, JG, MaG, TG, EG, JB, NS)

1991 Rochester (SL)

1992 Denver (JB)

2002 Minnesota (EG, TG, NL, SL, JG, MG, CPG, DG, MaG)

2002 Greenwood (SL, TG)

2009 Greenwood (DM)

IV V VI

1996 Mapping of gene - Xp22.11

(Arena et al., AJMG 64:50, 1996)

2003 Identification of gene- SMS

(Cason et al., Eur J Hum Gent 11:937, 2003)

2009 First treatment trial -

(Spermine Supplements)

Mexico

Canada

Brazil

Belgium

Switzerland

Italy

Snyder-Robinson Syndrome Clinical Manifestations

Growth

Birth (usually normal)

Adult height-variable (<3rd >9th centiles)

Adult weight (usually low)

Adult head circumference (usually large)


Development

Sit alone (delayed)

Walking alone (3 yr - never)

1st words (8 mo - never)

Phrases/sentences (3 yr - never)


Large head

Facial asymmetry

Mid-face flatness

High palate*

Prominent lower lip

Narrow chest

Pectus excavatum (sunken chest)

Kyphosis/scoliosis*

Long thin digits*

Hyperextensible fingers

Craniofacial & Skeletal Manifestations

Neurological Manifestations

Hypotonia*

Nasal speech*

Unsteady gait

Seizures (none - intractable)

Intellectual disability (none-severe)*



Brain Imaging

Enlarged ventricles

Small/thin corpus callosum

White matter volume loss


Possible Other Manifestations

Low/high blood sugar

Anemia

Thrombocytopenia

Heart defect (mild)

Fatty disposition in soft tissues

Osteoporosis*

snyder-robinson syndrome a 46 year odyssey

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