Abnormality of the skeletal system, and Narrow mouth

X-linked autism-6 is a neurodevelopmental disorder that affects only males. Some patients may respond favorably to carnitine supplementation (summary by Ziats et al., 2015).Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; {608638}) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).For a discussion of heterogeneity of autism, see {209850}.

AUTISM, SUSCEPTIBILITY TO, X-LINKED 6; AUTSX6 Is also known as tmlhed|epsilon-trimethyllysine hydroxylase deficiency

• Intellectual disability
• Seizures
• Ptosis
• Delayed speech and language development
• Atrial septal defect

SOURCES: OMIM MENDELIAN

Oral submucous fibrosis (OSMF) is a chronic, progressive disease that alters the fibroelasticity of the oral submucosa, prevalent in India and Southeast Asia but rare elsewhere, and characterized by burning and pain in the oral cavity, loss of gustatory sensation, the presence of blanched fibrous bands and stiffening of the oral mucosa and oro-pharynx (leading to trismus and a progressive reduction in mouth opening) and an increased risk of developing oral squamous cell cancer (3-19%). It is usually associated with the chewing of the areca nut (an ingredient in betel quid) but the exact etiology is unknown and there is currently no effective treatment.

ORAL SUBMUCOUS FIBROSIS Is also known as osmf

• Flexion contracture
• Narrow mouth
• Trismus
• Cheilitis
• Abnormality of the pharynx

SOURCES: MESH ORPHANET MENDELIAN

Digitotalar dysmorphism, also known as distal arthrogryposis type 1 (DA1), is an autosomal dominant congenital anomaly characterized by contractures of the distal regions of the hands and feet with no facial involvement or any additional anomalies. It is the most common type of distal arthrogryposis (see this term).

DIGITOTALAR DYSMORPHISM Is also known as ulnar drift, hereditary|da1|distal arthrogryposis type 1|da1a

• Flexion contracture
• Talipes equinovarus
• Narrow mouth
• Camptodactyly
• Joint stiffness

SOURCES: ORPHANET OMIM MENDELIAN

• Micrognathia
• Cryptorchidism
• Ptosis
• Low-set ears
• Narrow mouth

SOURCES: OMIM MENDELIAN

Carney complex-trismus-pseudocamptodactyly syndrome is a rare genetic heart-hand syndrome characterized by typical manifestations of the Carney complex (spotty pigmentation of the skin, familial cardiac and cutaneous myxomas and endocrinopathy) associated with trismus and distal arthrogryposis (presenting as involuntary contraction of distal and proximal interphalangeal joints of hands evident only on dorsiflexion of wrist and similar lower-limb contractures producing foot deformities).

CARNEY COMPLEX-TRISMUS-PSEUDOCAMPTODACTYLY SYNDROME Is also known as carney complex variant

• Short stature
• Talipes equinovarus
• Narrow mouth
• Camptodactyly of finger
• Freckling

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency is a rare, hereditary ataxia characterized by an early onset symptomatic generalized epilepsy, progressive cerebellar ataxia resulting in significant difficulties to walk or wheelchair dependency, and intellectual disability.

AUTOSOMAL RECESSIVE CEREBELLAR ATAXIA-EPILEPSY-INTELLECTUAL DISABILITY SYNDROME DUE TO TUD DEFICIENCY Is also known as scar23|spinocerebellar ataxia autosomal recessive type 23

• Intellectual disability
• Seizures
• Generalized hypotonia
• Ataxia
• Abnormal facial shape

SOURCES: ORPHANET OMIM MENDELIAN

Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (OMIM ) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic LeukemiaIn up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (OMIM ), KRAS (OMIM ), and NRAS (OMIM ) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26 ) have also been found in patients with JMML.About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1 ) due to germline mutations in the NF1 gene (OMIM ). In addition, patients with Noonan syndrome (NS1, {163950}; NS3, {609942}) or Noonan syndrome-like disorder (NSLL ) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic LeukemiaSomatic mutations in the CBL, ASXL1 (OMIM ), TET2 (OMIM ), and SF3B1 (OMIM ) genes have been found in patients with CMML.

JUVENILE MYELOMONOCYTIC LEUKEMIA Is also known as juvenile chronic myelomonocytic leukemia|jmml|leukemia, juvenile myelomonocytic

• Generalized hypotonia
• Abnormal facial shape
• Anemia
• Anteverted nares
• Splenomegaly

SOURCES: ORPHANET MESH OMIM MENDELIAN

Hamel cerebro-palato-cardiac syndrome is an X-linked intellectual disability syndrome (XLMR; see this term) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome (see this term).

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Micrognathia

SOURCES: ORPHANET MENDELIAN

Benign Samaritan congenital myopathy is a rare, genetic, skeletal muscle disease characterized by severe neonatal hypotonia with respiratory insufficiency, delay in motor milestones, and dysmorphic features including bitemporal narrowing, epicanthal folds and hypertelorism. Affected individuals show gradual improvement in hypotonia and muscle weakness within the first two years of life resulting in minimal clinical manifestations in adulthood.

• Generalized hypotonia
• Hypertelorism
• Motor delay
• Epicanthus
• Wide nasal bridge

SOURCES: ORPHANET MENDELIAN

Fraser syndrome is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract (summary by van Haelst et al., 2008).For a general phenotypic description and a discussion of genetic heterogeneity of Fraser syndrome, see {219000}.

• Hydrocephalus
• Syndactyly
• Narrow mouth
• Anal atresia
• Pulmonary hypoplasia

SOURCES: OMIM MENDELIAN