Beare-Stevenson Syndrome

Beare-Stevenson cutis gyrata syndrome is a genetic disorder characterized by skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis).


Mutations in the FGFR2 gene


The gene produces a protein called fibroblast growth factor receptor 2, which plays an important role in signaling a cell to respond to its environment, perhaps by dividing or maturing. A mutation in the FGFR2 gene alters the protein and promotes prolonged signaling, which is thought to interfere with skeletal and skin development. Not all patients with this syndrome have this mutation.


50% of cases, cutis gyrata, corduroy-like linear striations in the skin, acanthosis nigricans, skin tags, and choanal stenosis or atresia).

  • facial features similar to Crouzon disease,
  • ear defects (conductive hearing loss, posteriorly angulated ears, stenotic auditory canals, preauricular furrows, and narrow ear canals),
  • hirsutism,
  • a prominent umbilical stump, and
  • genitorurinary anomalies (anteriorly placed anus, hypoplasic labia, hypospadias).

Treatment and managment:

supportive care.


BSS is associated with a poor outcome as patients present an elevated risk for sudden death in their first year of life. Significant developmental delay and intellectual disability are observed in most patients who survive infancy.




Nemaline myopathy



A rare genetic muscle disorder. Six different clinical subtypes of nemaline myopathy have been identified based on disease severity and age of onset, ranging from a severe congenital-onset (at birth) form that is usually lethal in the first few months of life, through to less severe forms with onset in childhood or adulthood.

It is defined by muscle weakness and the presence of fine, thread-like or rod-like structures called “nemaline bodies”, when muscle biopsies are viewed under the microscope.  The prefix “nema-” is derived from Greek and means “thread-like.” Nemaline bodies consist of accumulations of muscle proteins due to mutations in genes which encode proteins components of the muscle thin filament.

Signs & Symptoms:

  • muscle weakness
  • diminished muscle tone (hypotonia)
  • reduced or absent reflexes.
  • Muscle weakness is usually most severe in muscles of the face, neck and proximal muscles. (The proximal muscles are the muscles that are closest to the center of the body such as the muscles of the shoulder, pelvis, and upper arms and legs.)
  • In most people, muscle weakness is static (nonprogressive) over time.
  • Weakness of the muscles of breathing and swallowing are the major cause of morbidity and mortality.

Clinical presentation:

  • affected individuals may develop distinctive facial features including an elongated face, a displaced jaw that is farther back than normal (retrognathia), and a highly-arched roof of the mouth (palate).
  • Muscle weakness may also cause difficulty speaking (dysarthria) and swallowing resulting in feeding difficulties.
  • Some infants with nemaline myopathy may require a feeding tube.
  • may develop abnormally fixed joints that occur when thickening and shortening of tissue such as muscle fibers cause deformity and restrict the movement of an affected area (contractures),
  • a sunken chest (pectus excavatum),
  • abnormal side-to-side-curvature of the spine (scoliosis) or abnormal rigidity of the spine.


Severe Congenital (Neonatal) Nemaline Myopathy

  • This form of nemaline myopathy is apparent at birth and accounts for approximately 16 percent of cases.
  • Affected infants have profound muscle weakness and severe hypotonia.
  • Infants with this form of nemaline myopathy experience difficulty sucking and swallowing leading to feeding difficulties,
  • show little spontaneous movement,
  •  exhibit respiratory insufficiency.
  • Some infants may experience the passage or backflow (reflux) of the contents of the stomach or small intestines into the esophagus (gastroesophageal reflux).

Intermediate Congenital Nemaline Myopathy

  • This form of nemaline myopathy is less severe than the severe congenital form and more severe than the typical congenital form.
  • It accounts for approximately 20 percent of cases.
  • The early development of contractures is characteristic of this form of nemaline myopathy.
  • As affected infants age, they often experience delays in attaining motor milestones or may not be able to sit up or walk independently.
  • Children with intermediate congenital nemaline myopathy often require a wheelchair or ongoing breathing (ventilatory) support during childhhood.

Childhood-Onset Nemaline Myopathy

  • This form of nemaline myopathy usually becomes apparent between 10-20 years of age and accounts for approximately 13 percent of cases.
  • The development of early motor skills is usually unaffected.
  • Sometime during the late teens or early twenties, affected individuals develop slowly progressive muscle weakness.
  • Affected individuals may be unable to bend the foot upward toward the leg (foot drop).
  • Eventually the entire ankle and lower legs muscles are involved. In one family with this form of nemaline myopathy, two members required wheelchairs by age 40.

Adult-Onset Nemaline Myopathy

  • The onset and severity of this form of nemaline myopathy varies.
  • It is extremely rare accounting for only 4 percent of cases.
  • It occurs in individuals between the ages of 20-50 who develop generalized muscle weakness that may progress rapidly.
  • Muscle pain (myalgia) may also occur.
  • Involvement of certain neck muscles may make it difficult to hold one’s head up and cause the head to drop.
  • Although uncommon, some individuals may develop respiratory or cardiac complications often in conjunction with increasing muscle weakness. This form of nemaline myopathy may be distinct form the genetic or inherited forms of the disorder.


Amish Nemaline Myopathy

  • This form of myopathy was identified in several related families within an Amish community.
  • Onset is shortly after birth and affected infants may have hypotonia, multiple contractures, and tremors, which usually diminish over the first few months of life.
  • Affected infants have progressive muscle weakness, a severely deformed chest with a prominent sternum (pectus carinatum), muscle wasting (atrophy) and life-threatening respiratory insufficiency.
  • Severe neonatal respiratory disease and the presence of arthrogryposis multiplex congenita (joint contractures, which are permanent shortening of a muscle) often lead to death in the second year of life.



  • Ten genes have been found to cause nemaline myopathy. Nemaline myopathy can be inherited as an autosomal recessive or dominant trait.
  • At least 50% of cases of nemaline myopathy follow autosomal recessive inheritance, and the remainder are inherited in an autosomal dominant manner or are sporadic (new dominant cases – the first occurrence in the family).


  • based upon a thorough clinical evaluation, a detailed patient and family history and identification of characteristic findings.
  • confirmed by the presence of thread- or rod-like structures (nemaline bodies) on muscle biopsy when stained with Gomori trichrome.
  • A biopsy is the surgical removal and microscopic evaluation of affected tissue. Increasingly the diagnosis is made or confirmed by molecular genetic testing for mutations in the genes known to cause nemaline myopathy.


  • No specific treatment exists for nemaline myopathy.
  • Treatment is supportive and directed toward the specific symptoms that are apparent in each individual.


Retrograde ejaculation

Retrograde ejaculation occurs when semen, which would, in most cases, be ejaculated via the urethra, is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation forcing the semen to exit via the urethra, the path of least resistance. When the bladder sphincter does not function properly, retrograde ejaculation may occur

During a male orgasm, sperm are released from the epididymis and travel via small tubes called the vas deferens. The sperm mix with seminal fluid in the seminal vesicles, prostate fluid from the prostate gland, and lubricants from the bulbourethral gland. During climax, muscles at the end of the bladder neck tighten to prevent retrograde flow of semen.

In retrograde ejaculation, these bladder neck muscles are either very weak or the nerves controlling the muscles have become damaged.


A malfunctioning bladder sphincter, leading to retrograde ejaculation, may be a result either of:

  • Autonomic nervous system dysfunction. (Dysautonomia)
  • Operation on the prostate. It is a common complication of transurethral resection of the prostate, a procedure in which prostate tissue is removed, slice by slice, through a resectoscope passed along the urethra.
  • a retroperitoneal lymph node dissection for testicular cancer if nerve pathways to the bladder sphincter are damaged, with the resulting retrograde ejaculation being either temporary or permanent.
  •  Surgery on the bladder neck accounted for about ten percent of the cases of retrograde ejaculation or anejaculation reported in a literature review.
  • due to a common side effect of medications, such as tamsulosin, that are used to relax the muscles of the urinary tract, treating conditions such as benign prostatic hyperplasia. By relaxing the bladder sphincter muscle, the likelihood of retrograde ejaculation is increased.
  • medications that mostly cause it are antidepressant and antipsychotic medication, as well as NRIs such as atomoxetine; patients experiencing this phenomenon tend to quit the medications.

Retrograde ejaculation can also be a complication of diabetes, especially in cases of diabetics with long term poor blood sugar control. This is due to neuropathy of the bladder sphincter.


pudendal nerves

The pudendal nerve is the main nerve of the perineum.[1]:274 It carries sensation from the external genitalia of both sexes and the skin around the anus and perineum, as well the motor supply to various pelvic muscles, including the male or female external urethral sphincter and the external anal sphincter. If damaged, most commonly by childbirth, lesions may cause sensory loss or fecal incontinence. The nerve may be temporarily blocked as part of an anaesthetic procedure.image

Joubert syndrome

imageimageimage is disorder of brain development that may affect many parts of the body. It is characterized by the absence or underdevelopment of the cerebellar vermis (a part of the brain that controls balance and coordination) and a malformed brain stem (connection between the brain and spinal cord). Together, these cause the characteristic appearance of a molar tooth sign on MRI. Signs and symptoms can vary but commonly include weak muscle tone (hypotonia); abnormal breathing patterns; abnormal eye movements; ataxia; distinctive facial features; and intellectual disability.Various other abnormalities may also be present. Joubert syndrome may be caused by mutations in any of many genes. Inheritance is usually autosomal recessive, but rarely it may be X-linked recessive. Treatment is supportive and depends on the symptoms in each person.”