Downslanted palpebral fissures, and Joint laxity

Intellectual developmental disorder with persistence of fetal hemoglobin is characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin (HbF) (summary by Dias et al., 2016).Many of these features overlap with chromosome 2p16.1-p15 deletion syndrome (OMIM ).

INTELLECTUAL DEVELOPMENTAL DISORDER WITH PERSISTENCE OF FETAL HEMOGLOBIN Is also known as dias-logan syndrome|intellectual developmental disorder with hereditary persistence of fetal hemoglobin

• Intellectual disability
• Global developmental delay
• Microcephaly
• Strabismus
• Low-set ears

SOURCES: OMIM MENDELIAN

Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A ), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS ), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015).

PMP22-RAI1 CONTIGUOUS GENE DUPLICATION SYNDROME Is also known as trisomy 17p11.2-p12|dup(17)(p11.2p12)|trisomy 17p11.2p12|yuan-harel-lupski syndrome|17p11.2p12 microduplication syndrome

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Failure to thrive
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Ehlers-Danlos syndrome, spondylocheirodysplastic type is a subtype of Ehlers-Danlos syndrome characterized by skeletal dysplasia comprising platyspondyly with moderate short stature, osteopenia and widened metaphyses, in addition to hyperextensible, thin, easily bruised skin, hypermobility of small joints with tendency to contractures, prominent eyes with bluish sclerae, wrinkled palms, atrophy of the thenar muscle and tapering fingers.

EHLERS-DANLOS SYNDROME, SPONDYLOCHEIRODYSPLASTIC TYPE Is also known as eds, spondylocheirodysplastic type|spondylocheirodysplasia, ehlers-danlos syndrome-like|scd-eds

• Short stature
• Growth delay
• Failure to thrive
• Flexion contracture
• High palate

SOURCES: MESH OMIM ORPHANET MENDELIAN

Gabriele-de Vries syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable cognitive impairment, often with behavioral problems, feeding problems, some movement abnormalities, and dysmorphic facial features. Affected individuals may also have a variety of congenital abnormalities (summary by Gabriele et al., 2017).

GABRIELE-DE VRIES SYNDROME Is also known as yy1 haploinsufficiency syndrome

• Intellectual disability
• Global developmental delay
• Growth delay
• Micrognathia
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Noonan syndrome-like disorder with loose anagen hair is characterized by facial features similar to those observed in Noonan syndrome (OMIM ), including hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly angulated ears, and overfolded pinnae. In addition, patients display short stature, frequently with growth hormone (GH; see {139250}) deficiency; cognitive deficits; relative macrocephaly; small posterior fossa resulting in Chiari I malformation; hypernasal voice; cardiac defects, especially dysplasia of the mitral valve and septal defects; and ectodermal abnormalities, in which the most characteristic feature is the hair anomaly, including easily pluckable, sparse, thin, slow-growing hair (summary by Bertola et al., 2017). Genetic Heterogeneity of Noonan Syndrome-Like Disorder with Loose Anagen HairNSLH2 (OMIM ) is caused by mutation in the PPP1CB gene (OMIM ) on chromosome 2p23.

NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR 1; NSLH1 Is also known as tosti syndrome|nslh

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hypertelorism

SOURCES: OMIM MENDELIAN

Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations.

SYNDROMIC MICROPHTHALMIA TYPE 5 Is also known as mcops5|syndromic microphthalmia/anophthalmia due to otx2 mutation

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: MESH OMIM ORPHANET MENDELIAN

Autosomal recessive cutis laxa type IB (ARCL1B) is characterized by the presence of severe systemic connective tissue abnormalities, including emphysema, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels. All symptoms refer to disturbed elastic fiber formation (summary by Hoyer et al., 2009).For a complete phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (OMIM ).

• Generalized hypotonia
• Microcephaly
• Hypertelorism
• Micrognathia
• Abnormal facial shape

SOURCES: OMIM MENDELIAN

Autosomal recessive cutis laxa type 2B is a rare, hereditary, developmental defect with connective tissue involvement characterized by cutis laxa of variable severity, in utero growth restriction, congenital hip dislocation and joint hyperlaxity, wrinkling of the skin, in particular the dorsum of hands and feet, and progeroid facial features. Hypotonia, developmental delay, and intellectual disability are common. In addition, cataracts, corneal clouding, wormian bones, lipodystrophy and osteopenia have been reported.

AUTOSOMAL RECESSIVE CUTIS LAXA TYPE 2B Is also known as autosomal recessive cutis laxa type 2, progeroid type|cutis laxa with progeroid features|arcl2, progeroid type|arcl2b

• Intellectual disability
• Global developmental delay
• Microcephaly
• Scoliosis
• Growth delay

SOURCES: OMIM ORPHANET MESH MENDELIAN

Loeys-Dietz syndrome is a rare genetic connective tissue disorder characterized by a broad spectrum of craniofacial, vascular and skeletal manifestations with four genetic subtypes described forming a clinical continuum.

LOEYS-DIETZ SYNDROME Is also known as aortic aneurysm syndrome due to tgf-beta receptors anomalies|aneurysm, aortic and cerebral, with arterial tortuosity and skeletal manifestations

• Scoliosis
• Hypertelorism
• Micrognathia
• High palate
• Downslanted palpebral fissures

SOURCES: OMIM ORPHANET MENDELIAN

TMEM165-CDG is a form of congenital disorders of N-linked glycosylation characterized by a psychomotor delay-dysmorphism (pectus carinatum, dorsolumbar kyphosis and severe sinistroconvex scoliosis, short distal phalanges, genua vara, pedes planovalgi syndrome) with postnatal growth deficiency and major spondylo-, epi-, and metaphyseal skeletal involvement. Additional features include facial dysmorphism (midface hypoplasia, internal strabism of the right eye, low-set ears, moderately high arched palate, small teeth), nephrotic syndrome, cardiac defects, and feeding problems. The disease is caused by mutations in the gene TMEM165 (4q12).

TMEM165-CDG Is also known as congenital disorder of glycosylation type 2k|cdg iik|cdg2k|congenital disorder of glycosylation type iik|cdg-iik|cdgiik|cdg syndrome type iik|carbohydrate deficient glycoprotein syndrome type iik

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN