Failure to thrive, and Retrognathia

High match SECKEL SYNDROME 4; SCKL4

Seckel syndrome is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, severe microcephaly with mental retardation, and specific dysmorphic features (Faivre et al., 2002).For a general description and a discussion of genetic heterogeneity of Seckel syndrome, see {210600}.

• Intellectual disability
• Short stature
• Microcephaly
• Growth delay
• Failure to thrive

SOURCES: OMIM MENDELIAN

High match INTELLECTUAL DISABILITY-SEVERE SPEECH DELAY-MILD DYSMORPHISM SYNDROME

Intellectual disability-severe speech delay-mild dysmorphism syndrome is a rare, genetic, syndromic intellectual disability disorder, with highly variable phenotype, typically characterized by mild to severe global development delay, severe speech and language impairment, mild to severe intellectual disability, dysphagia, hypotonia, relative to true macrocephaly, and behavioral problems that may include autistic features, hyperactivity, and mood lability. Facial gestalt typically features a broad, prominent forehead, hypertelorism, downslanting palpebral fissures, ptosis, a short bulbous nose with broad tip, thick vermilion border, wide, and open mouth with downturned corners. Brain, cardiac, urogenital and ocular malformations may be associated.

INTELLECTUAL DISABILITY-SEVERE SPEECH DELAY-MILD DYSMORPHISM SYNDROME Is also known as foxp1 syndrome

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hypertelorism
• Nystagmus

SOURCES: ORPHANET OMIM MENDELIAN

High match CLASSIC MULTIMINICORE MYOPATHY

CLASSIC MULTIMINICORE MYOPATHY Is also known as classic multiminicore disease|classic mmd

• Short stature
• Generalized hypotonia
• Scoliosis
• Failure to thrive
• High palate

SOURCES: ORPHANET MENDELIAN

High match SQUALENE SYNTHASE DEFICIENCY; SQSD

Squalene synthase deficiency is an autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, and facial dysmorphisms, as well as low total and LDL-cholesterol and abnormal urine organic acids (Coman et al., 2018). Squalene synthase deficiency has been reported in 3 patients from 2 families.

SQUALENE SYNTHASE DEFICIENCY; SQSD Is also known as neurodevelopmental disorder with low cholesterol and abnormal urine organic acids

• Seizures
• Global developmental delay
• Failure to thrive
• Micrognathia
• Cataract

SOURCES: OMIM MENDELIAN

High match MENTAL RETARDATION, AUTOSOMAL DOMINANT 22; MRD22

Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severe mental retardation, limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may be explained in some cases by incomplete penetrance or variable expressivity (summary by Ballif et al., 2012).Patients with autosomal dominant mental retardation-22 have a phenotype similar to that in patients with chromosome 1q43-q44 deletion syndrome (de Munnik et al., 2014).

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

SOURCES: MESH OMIM MENDELIAN

High match SHORT STATURE, RHIZOMELIC, WITH MICROCEPHALY, MICROGNATHIA, AND DEVELOPMENTAL DELAY; SRMMD

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

SOURCES: OMIM MENDELIAN

High match MOGS-CDG

MOGS-CDG is a form of congenital disorders of N-linked glycosylation characterized by generalized hypotonia, craniofacial dysmorphism (prominent occiput, short palpebral fissures, long eyelashes, broad nose, high arched palate , retrognathia), hypoplastic genitalia, seizures, feeding difficulties, hypoventilation, severe hypogammaglobulinemia with generalized edema, and increased resistance to particular viral infections (particularly to enveloped viruses). The disease is caused by loss-of-function mutations in the gene MOGS (2p13.1).

MOGS-CDG Is also known as glucosidase i deficiency|cdg-iib|cdgiib|cdg iib|carbohydrate deficient glycoprotein syndrome type iib|congenital disorder of glycosylation type 2b|cdg2b|glucosidase 1 deficiency|congenital disorder of glycosylation type iib|cdg syndrome type iib

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Scoliosis

SOURCES: MESH OMIM ORPHANET MENDELIAN

High match PROGEROID AND MARFANOID ASPECT-LIPODYSTROPHY SYNDROME

Progeroid and marfanoid aspect-lipodystrophy syndrome is a rare systemic disease characterized by a neonatal progeroid appearance (not associated with other manifestations of premature aging) associated with facial dysmorphism (e.g. macrocephaly or arrested hydrocephaly, proptosis, downslanting palpebral fissures, retrognathia), generalized, extreme, congenital lack of subcutaneous fat tissue (except in the breast and iliac region) and incomplete signs of Marfan syndrome (mainly severe myopia, joint hyperextensibility and arachnodactyly). Metabolic disturbances are not associated.

PROGEROID AND MARFANOID ASPECT-LIPODYSTROPHY SYNDROME Is also known as marfanoid-progeroid syndrome|marfan-progeroid-lipodystrophy syndrome

• Growth delay
• Failure to thrive
• Abnormal facial shape
• Hypertension
• Myopia

SOURCES: ORPHANET OMIM MENDELIAN

High match MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 3; MMDS3

MMDS3 is an autosomal recessive severe neurodegenerative disorder characterized by loss of previously acquired developmental milestones in the first months or years of life. Some affected patients have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some patients die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some patients may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable. There may be additional biochemical evidence of mitochondrial dysfunction (summary by Liu et al., 2018).For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (OMIM ).

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM MENDELIAN

High match AUTISM SPECTRUM DISORDER DUE TO AUTS2 DEFICIENCY

Autism spectrum disorder due to AUTS2 deficiency is a rare genetic syndromic intellectual disability characterized by global developmental delay and borderline to severe intellectual disability, autism spectrum disorder with obsessive behavior, stereotypies, hyperactivity but frequently friendly and affable personality, feeding difficulties, short stature, muscular hypotonia, microcephaly, characteristic dysmorphic features (hypertelorism, high arched eyebrows, ptosis, deep and/or broad nasal bridge, broad/prominent nasal tip, short and/or upturned philtrum, narrow mouth, and micrognathia), and skeletal anomalies (kyphosis and/or scoliosis, arthrogryposis, slender habitus and extremities). Other clinical features may include hernias, congenital heart defects, cryptorchidism and seizures.

AUTISM SPECTRUM DISORDER DUE TO AUTS2 DEFICIENCY Is also known as asd due to auts2 deficiency|auts2 syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN