Hydrocephalus, and Dyspnea

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (OMIM ), collectively known as 'dystroglycanopathies' (Beltran-Valero de Bernabe et al., 2004).For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (OMIM ).

MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 5; MDDGA5 Is also known as walker-warburg syndrome or muscle-eye-brain disease, fkrp-related

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Cataract
• Feeding difficulties

SOURCES: OMIM MENDELIAN

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of PCD patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy; see these terms).

PRIMARY CILIARY DYSKINESIA Is also known as ics|polynesian bronchiectasis|ciliary dyskinesia, primary, 1, with or without situs inversus|pcd|immotile cilia syndrome

• Hearing impairment
• Ventriculomegaly
• Respiratory distress
• Hydrocephalus
• Headache

SOURCES: ORPHANET OMIM MENDELIAN

Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterized by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness.

STEINERT MYOTONIC DYSTROPHY Is also known as dm1|md1|myotonic dystrophy type 1|steinert disease

• Strabismus
• Muscular hypotonia
• Cataract
• Cryptorchidism
• Skeletal muscle atrophy

SOURCES: ORPHANET MENDELIAN

Pfeiffer syndrome type 2 (PS2) is a frequent and severe type of Pfeiffer syndrome (PS; see this term), characterized by cloverleaf skull, severe associated functional disorders, and hand/foot and elbow/knee abnormalities.

• Intellectual disability
• Seizures
• Global developmental delay
• Hypertelorism
• Cleft palate

SOURCES: ORPHANET MENDELIAN

Lymphangioleiomyomatosis (LAM) is a multiple cystic lung disease characterized by progressive cystic destruction of the lung and lymphatic abnormalities, frequently associated with renal angiomyolipomas (AMLs). LAM occurs either sporadically or as a manifestation of tuberous sclerosis complex (TSC).

LYMPHANGIOLEIOMYOMATOSIS Is also known as lam|lymphangiomyomatosis

• Seizures
• Pain
• Cognitive impairment
• Fever
• Optic atrophy

SOURCES: OMIM ORPHANET MESH MENDELIAN

Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, {218330}).For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (OMIM ).

• Intellectual disability
• Short stature
• Hepatomegaly
• Brachydactyly
• Abnormality of the skeletal system

SOURCES: OMIM MENDELIAN

Gaucher disease - ophthalmoplegia - cardiovascular calcification is a variant of Gaucher disease, also known as a Gaucher-like disease that is characterized by cardiac involvement.

GAUCHER DISEASE-OPHTHALMOPLEGIA-CARDIOVASCULAR CALCIFICATION SYNDROME Is also known as cardiovascular gaucher disease|gaucher-like disease|gaucher disease type 3c

• Seizures
• Global developmental delay
• Short stature
• Hearing impairment
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Holoprosencephaly-9 refers to a disorder characterized by a wide phenotypic spectrum of brain developmental defects, with or without overt forebrain cleavage abnormalities. It usually includes midline craniofacial anomalies involving the first branchial arch and/or orbits, pituitary hypoplasia with panhypopituitarism, and postaxial polydactyly. The disorder shows incomplete penetrance and variable expressivity (summary by Roessler et al., 2003 and Bertolacini et al., 2012).For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (OMIM ).

HOLOPROSENCEPHALY 9; HPE9 Is also known as holoprosencephaly with microphthalmia and first branchial arch anomalies|pituitary anomalies with holoprosencephaly-like features

• Seizures
• Global developmental delay
• Short stature
• Microcephaly
• Cryptorchidism

SOURCES: OMIM MENDELIAN

ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures (summary by Gueneau et al., 2018).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM MENDELIAN

Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), while TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1) (Langer et al., 1987).

THANATOPHORIC DYSPLASIA, TYPE I; TD1 Is also known as thanatophoric dysplasia|lethal short-limbed platyspondylic dwarfism, san diego type|thanatophoric dwarfism|td|platyspondylic lethal skeletal dysplasia, san diego type

• Seizures
• Global developmental delay
• Hearing impairment
• Growth delay
• Muscular hypotonia

SOURCES: OMIM MENDELIAN