X-linked intellectual disability, Siderius type

Alternate names[edit]

MRXSSD; Intellectual deficit X-linked Siderius type; Siderius Hamel syndrome

Definition[edit]

X-linked intellectual disability, Siderius type is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present.

Epidemiology[edit]

The syndrome has been described in seven boys from two families.

Cause[edit]

X-linked intellectual disability, Siderius type is caused by mutations in the PHF8 gene.
This gene provides instructions for making a protein that is found in the nucleus of cells, particularly in brain cells before and just after birth.

Inheritance[edit]

File:X-linked recessive (2).svg

X-linked recessive inheritance

This condition is inherited in an X-linked recessive pattern.

Signs and symptoms[edit]

This condition is characterized by mild to moderate intellectual disability that affects only males.
Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed.
Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate).
A cleft can occur on one or both sides of the upper lip.
Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures).
Affected individuals may also have low-set ears and large hands.

Diagnosis[edit]

Treatment[edit]

X-linked disorders

Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton)

Arrestin

* Oguchi disease 1

Myelin

* Pelizaeus–Merzbacher disease

Pulmonary surfactant

* Surfactant metabolism dysfunction 1, 2

Cell adhesion molecule

IgSF CAM:	* OFC7
Integrin:	* cell surface receptor deficiencies

Tetraspanin

* TSPAN7

See also other cell membrane proteins

Deficiencies of intracellular signaling peptides and proteins

GTP-binding protein regulators

GTPase-activating protein	* Neurofibromatosis type I Watson syndrome Tuberous sclerosis
Guanine nucleotide exchange factor	* Marinesco–Sjögren syndrome Aarskog–Scott syndrome Juvenile primary lateral sclerosis X-Linked mental retardation 1

G protein

Heterotrimeic	* cAMP/GNAS1: Pseudopseudohypoparathyroidism Progressive osseous heteroplasia Pseudohypoparathyroidism Albright's hereditary osteodystrophy McCune–Albright syndrome CGL 2
Monomeric	* RAS: HRAS Costello syndrome KRAS Noonan syndrome 3 KRAS Cardiofaciocutaneous syndrome RAB: RAB7 Charcot–Marie–Tooth disease RAB23 Carpenter syndrome RAB27 Griscelli syndrome type 2 RHO: RAC2 Neutrophil immunodeficiency syndrome ARF: SAR1B Chylomicron retention disease ARL13B Joubert syndrome 8 ARL6 Bardet–Biedl syndrome 3

MAP kinase

* Cardiofaciocutaneous syndrome

See also intracellular signaling peptides and proteins

Genetic disorders relating to deficiencies of transcription factor or coregulators

(1) Basic domains

1.2	* Feingold syndrome Saethre–Chotzen syndrome
1.3	* Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	* (Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis
2.2	* Barakat syndrome Tricho–rhino–phalangeal syndrome
2.3	* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2
2.5	* Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	* ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome
3.2	* PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3
3.3	* FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX
3.5	* IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	* Hyperimmunoglobulin E syndrome
4.3	* Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome
4.7	* Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome
4.11	* Cleidocranial dysostosis

(0) Other transcription factors

0.6	* Kabuki syndrome

Inherited disorders of trafficking / vesicular transport proteins

Vesicle formation

Lysosome/Melanosome:	* HPS1–HPS7 Hermansky–Pudlak syndrome LYST Chédiak–Higashi syndrome
COPII:	* SEC23A Cranio-lenticulo-sutural dysplasia
APC:	* AP1S2 X-linked intellectual disability AP3B1 Hermansky–Pudlak syndrome 2 AP4M1 CPSQ3

Rab

Cytoskeleton

Myosin:	* MYO5A Griscelli syndrome 1
Microtubule:	* SPG4 Hereditary spastic paraplegia 4
Kinesin:	* KIF5A Hereditary spastic paraplegia 10
Spectrin:	* SPTBN2 Spinocerebellar ataxia 5

Vesicle fusion

Synaptic vesicle:	* SNAP29 CEDNIK syndrome STX11 Hemophagocytic lymphohistiocytosis 4
Caveolae:	* CAV1 Congenital generalized lipodystrophy 3 CAV3 Limb-girdle muscular dystrophy 2B, Long QT syndrome 9
Vacuolar protein sorting:	* VPS33B ARC syndrome VPS13B Cohen syndrome

See also vesicular transport proteins

NIH genetic and rare disease info[edit]

NIH info on X-linked intellectual disability, Siderius type

X-linked intellectual disability, Siderius type is a rare disease.

Rare and genetic diseases

Rare diseases - X-linked intellectual disability, Siderius type

A-Z list of rare diseases	* 0-9 \| A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z
Also see	* Comprehensive list of genetic and rare diseases
Resources	* NIH GARD, US Genetic and Rare Diseases Info Rare Disease Day Undiagnosed Diseases Network Database of rare diseases at Orphanet Rare Disease UK Rare diseases search engine

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